Compositions and methods for the therapy and diagnosis of ovarian cancer

This application is a continuation-in-part of U.S. application Ser. No. 09/636,801, filed Aug. 10, 2000, now abandoned, which is a continuation-in part of U.S. application Ser. No. 09/617,747, filed Jul. 17, 2000, now abandoned which is a continuation-in-part of U.S. application Ser. No. 09/404,879, filed Sep. 24, 1999, U.S. Pat. No. 6,468,546, which is a continuation-in-part of U.S. application Ser. No. 09/338,933, filed Jun. 23, 1999, U.S. Pat. No. 6,488,931, which is a continuation-in-part of U.S. application Ser. No. 09/216,003, filed Dec. 17, 1998, and Ser. No. 09/215,681, filed Dec. 17, 1998, U.S. Pat. No. 6,528,253.

The present invention relates generally to ovarian cancer therapy. The invention is more specifically related to polypeptides comprising at least a portion of an ovarian carcinoma protein, and to polynucleotides encoding such polypeptides, as well as antibodies and immune system cells that specifically recognize such polypeptides. Such polypeptides, polynucleotides, antibodies and cells may be used in vaccines and pharmaceutical compositions for treatment of ovarian cancer.

Ovarian cancer is a significant health problem for women in the United States and throughout the world. Although advances have been made in detection and therapy of this cancer, no vaccine or other universally successful method for prevention or treatment is currently available. Management of the disease currently relies on a combination of early diagnosis and aggressive treatment, which may include one or more of a variety of treatments such as surgery, radiotherapy, chemotherapy and hormone therapy. The course of treatment for a particular cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumor markers. However, the use of established markers often leads to a result that is difficult to interpret, and high mortality continues to be observed in many cancer patients.

Immunotherapies have the potential to substantially improve cancer treatment and survival. Such therapies may involve the generation or enhancement of an immune response to an ovarian carcinoma antigen. However, to date, relatively few ovarian carcinoma antigens are known and the generation of an immune response against such antigens has not been shown to be therapeutically beneficial.

Accordingly, there is a need in the art for improved methods for identifying ovarian tumor antigens and for using such antigens in the therapy of ovarian cancer. The present invention fulfills these needs and further provides other related advantages.

Briefly stated, this invention provides compositions and methods for the therapy of cancer, such as ovarian cancer. In one aspect, the present invention provides polypeptides comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished. Within certain embodiments, the ovarian carcinoma protein comprises a sequence that is encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs:1-81, 313-331, 359, 366, 379, 385-387, 391 and complements of such polynucleotides.

The present invention further provides polynucleotides that encode a polypeptide as described above or a portion thereof, expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors.

Within other aspects, the present invention provides pharmaceutical compositions and vaccines. Pharmaceutical compositions may comprise a physiologically acceptable carrier or excipient in combination with one or more of: (i) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs:1-81, 313-331, 359, 366, 379, 385-387 or 391; (ii) a polynucleotide encoding such a polypeptide; (iii) an antibody that specifically binds to such a polypeptide; (iv) an antigen-presenting cell that expresses such a polypeptide and/or (v) a T cell that specifically reacts with such a polypeptide. Vaccines may comprise a non-specific immune response enhancer in combination with one or more of: (i) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs:1-81, 313-331, 359, 366, 379, 385-387 or 391; (ii) a polynucleotide encoding such a polypeptide; (iii) an anti-idiotypic antibody that is specifically bound by an antibody that specifically binds to such a polypeptide; (iv) an antigen-presenting cell that expresses such a polypeptide and/or (v) a T cell that specifically reacts with such a polypeptide.

The present invention further provides, in other aspects, fusion proteins that comprise at least one polypeptide as described above, as well as polynucleotides encoding such fusion proteins.

Within related aspects, pharmaceutical compositions comprising a fusion protein or polynucleotide encoding a fusion protein in combination with a physiologically acceptable carrier are provided.

Vaccines are further provided, within other aspects, comprising a fusion protein or polynucleotide encoding a fusion protein in combination with a non-specific immune response enhancer.

Within further aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, comprising administering to a patient a pharmaceutical composition or vaccine as recited above.

The present invention further provides, within other aspects, methods for stimulating and/or expanding T cells, comprising contacting T cells with (a) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs:1-387 or 391; (b) a polynucleotide encoding such a polypeptide and/or (c) an antigen presenting cell that expresses such a polypeptide under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells. Such polypeptide, polynucleotide and/or antigen presenting cell(s) may be present within a pharmaceutical composition or vaccine, for use in stimulating and/or expanding T cells in a mammal.

Within other aspects, the present invention provides methods for inhibiting the development of ovarian cancer in a patient, comprising administering to a patient T cells prepared as described above.

Within further aspects, the present invention provides methods for inhibiting the development of ovarian cancer in a patient, comprising the steps of: (a) incubating CD4 + and/or CD8 + T cells isolated from a patient with one or more of: (i) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs: 1-387 or 391; (ii) a polynucleotide encoding such a polypeptide; or (iii) an antigen-presenting cell that expresses such a polypeptide; such that T cells proliferate; and (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of ovarian cancer in the patient. The proliferated cells may be cloned prior to administration to the patient.

The present invention also provides, within other aspects, methods for identifying secreted tumor antigens. Such methods comprise the steps of: (a) implanting tumor cells in an immunodeficient mammal; (b) obtaining serum from the immunodeficient mammal after a time sufficient to permit secretion of tumor antigens into the serum; (c) immunizing an immunocompetent mammal with the serum; (d) obtaining antiserum from the immunocompetent mammal; and (e) screening a tumor expression library with the antiserum, and therefrom identifying a secreted tumor antigen. A preferred method for identifying a secreted ovarian carcinoma antigen comprises the steps of: (a) implanting ovarian carcinoma cells in a SCID mouse; (b) obtaining serum from the SCID mouse after a time sufficient to permit secretion of ovarian carcinoma antigens into the serum; (c) immunizing an immunocompetent mouse with the serum; (d) obtaining antiserum from the immunocompetent mouse; and (e) screening an ovarian carcinoma expression library with the antiserum, and therefrom identifying a secreted ovarian carcinoma antigen.

The present invention also discloses antibody epitopes recognized by the O8E polyclonal anti-sera which epitopes are presented herein as SEQ ID NOs: 394-415.

Further disclosed by the present invention are 10-mer and 9-mer peptides predicted to bind HLA-0201 which peptides are disclosed herein as SEQ ID NOs: 416-435 and SEQ ID NOs: 436-455, respectively.

These and other aspects of the present invention will become apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

FIGS. 1A-1S (SEQ ID NOs:1-71) depict partial sequences of polynucleotides encoding representative secreted ovarian carcinoma antigens.

FIGS. 2A-2C depict full insert sequences for three of the clones of FIG. 1 . FIG. 2A shows the sequence designated O7E (11731; SEQ ID NO:72), FIG. 2B shows the sequence designated O9E (11785; SEQ ID NO:73) and FIG. 2C shows the sequence designated O8E (13695; SEQ ID NO:74).

FIG. 3 presents results of microarray expression analysis of the ovarian carcinoma sequence designated O8E.

FIG. 4 presents a partial sequence of a polynucleotide (designated 3g; SEQ ID NO:75) encoding an ovarian carcinoma sequence that is a splice fusion between the human T-cell leukemia virus type I oncoprotein TAX and osteonectin.

FIG. 5 presents the ovarian carcinoma polynucleotide designated 3f (SEQ ID NO:76).

FIG. 6 presents the ovarian carcinoma polynucleotide designated 6b (SEQ ID NO:77).

FIGS. 7A and 7B present the ovarian carcinoma polynucleotides designated 8e (SEQ ID NO:78) and 8h (SEQ ID NO:79).

FIG. 8 presents the ovarian carcinoma polynucleotide designated 12c (SEQ ID NO:80).

FIG. 9 presents the ovarian carcinoma polynucleotide designated 12h (SEQ ID NO:81).

FIG. 10 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 3f.

FIG. 11 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 6b.

FIG. 12 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 8e.

FIG. 13 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 12c.

FIG. 14 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 12h.

FIGS. 15 A- 15 E- 2 depict partial sequences of additional polynucleotides encoding representative secreted ovarian carcinoma antigens (SEQ ID NOs:82-310).

FIG. 16 is a diagram illustrating the location of various partial O8E sequences within the full length sequence.

FIG. 17 is a graph illustrating the results of epitope mapping studies on O8E protein.

FIG. 18 is graph of a fluorescence activated cell sorting (FACS) analysis of O8E cell surface expression.

FIG. 19 is graph of a FACS analysis of O8E cell surface expression.

FIG. 20 shows FACS analysis results for O8E transfected HEK293 cells demonstrating cell surface expression of O8E.

FIG. 21 shows FACS analysis results for SKBR3 breast tumor cells demonstrating cell surface expression of O8E.

FIG. 22 shows O8E expression in HEK 293 cells. The cells were probed with anti-O8E rabbit polyclonal antisera #2333L.

FIG. 23 shows the ELISA analysis of anti-O8E rabbit sera.

FIG. 24 shows the ELISA analysis of affinity purified rabbit anti-O8E polyclonal antibody.

As noted above, the present invention is generally directed to compositions and methods for the therapy of cancer, such as ovarian cancer. The compositions described herein may include immunogenic polypeptides, polynucleotides encoding such polypeptides, binding agents such as antibodies that bind to a polypeptide, antigen presenting cells (APCs) and/or immune system cells (e.g., T cells).

Polypeptides of the present invention generally comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof. Certain ovarian carcinoma proteins have been identified using an immunoassay technique, and are referred to herein as ovarian carcinoma antigens. An “ovarian carcinoma antigen” is a protein that is expressed by ovarian tumor cells (preferably human cells) at a level that is at least two fold higher than the level in normal ovarian cells. Certain ovarian carcinoma antigens react detectably (within an immunoassay, such as an ELISA or Western blot) with antisera generated against serum from an immunodeficient animal implanted with a human ovarian tumor. Such ovarian carcinoma antigens are shed or secreted from an ovarian tumor into the sera of the immunodeficient animal. Accordingly, certain ovarian carcinoma antigens provided herein are secreted antigens. Certain nucleic acid sequences of the subject invention generally comprise a DNA or RNA sequence that encodes all or a portion of such a polypeptide, or that is complementary to such a sequence.

The present invention further provides ovarian carcinoma sequences that are identified using techniques to evaluate altered expression within an ovarian tumor. Such sequences may be polynucleotide or protein sequences. Ovarian carcinoma sequences are generally expressed in an ovarian tumor at a level that is at least two fold, and preferably at least five fold, greater than the level of expression in normal ovarian tissue, as determined using a representative assay provided herein. Certain partial ovarian carcinoma polynucleotide sequences are presented herein. Proteins encoded by genes comprising such polynucleotide sequences (or complements thereof) are also considered ovarian carcinoma proteins.

Antibodies are generally immune system proteins, or antigen-binding fragments thereof, that are capable of binding to at least a portion of an ovarian carcinoma polypeptide as described herein. T cells that may be employed within the compositions provided herein are generally T cells (e.g., CD4 + and/or CD8 + ) that are specific for such a polypeptide. Certain methods described herein further employ antigen-presenting cells (such as dendritic cells or macrophages) that express an ovarian carcinoma polypeptide as provided herein.

Ovarian Carcinoma Polynucleotides

Any polynucleotide that encodes an ovarian carcinoma protein or a portion or other variant thereof as described herein is encompassed by the present invention. Preferred polynucleotides comprise at least 15 consecutive nucleotides, preferably at least 30 consecutive nucleotides, and more preferably at least 45 consecutive nucleotides, that encode a portion of an ovarian carcinoma protein. More preferably, a polynucleotide encodes an immunogenic portion of an ovarian carcinoma protein, such as an ovarian carcinoma antigen. Polynucleotides complementary to any such sequences are also encompassed by the present invention. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) or RNA molecules. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present invention, and a polynucleotide may, but need not, be linked to other molecules and/or support materials.

Polynucleotides may comprise a native sequence (i.e., an endogenous sequence that encodes an ovarian carcinoma protein or a portion thereof) or may comprise a variant of such a sequence. Polynucleotide variants may contain one or more substitutions, additions, deletions and/or insertions such that the immunogenicity of the encoded polypeptide is not diminished, relative to a native ovarian carcinoma protein. The effect on the immunogenicity of the encoded polypeptide may generally be assessed as described herein. Variants preferably exhibit at least about 70% identity, more preferably at least about 80% identity and most preferably at least about 90% identity to a polynucleotide sequence that encodes a native ovarian carcinoma protein or a portion thereof.

The percent identity for two polynucleotide or polypeptide sequences may be readily determined by comparing sequences using computer algorithms well known to those of ordinary skill in the art, such as Megalign, using default parameters. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, or 40 to about 50, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Optimal alignment of sequences for comparison may be conducted, for example, using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, Wis.), using default parameters. Preferably, the percentage of sequence identity is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the window may comprise additions or deletions (i.e., gaps) of 20% or less, usually 5 to 15%, or 10 to 12%, relative to the reference sequence (which does not contain additions or deletions). The percent identity may be calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size) and multiplying the results by 100 to yield the percentage of sequence identity.

Variants may also, or alternatively, be substantially homologous to a native gene, or a portion or complement thereof. Such polynucleotide variants are capable of hybridizing under moderately stringent conditions to a naturally occurring DNA sequence encoding a native ovarian carcinoma protein (or a complementary sequence). Suitable moderately stringent conditions include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS.

It will be appreciated by those of ordinary skill in the art that, as a result of the degeneracy of the genetic code, there are many nucleotide sequences that encode a polypeptide as described herein. Some of these polynucleotides bear minimal homology to the nucleotide sequence of any native gene. Nonetheless, polynucleotides that vary due to differences in codon usage are specifically contemplated by the present invention. Further, alleles of the genes comprising the polynucleotide sequences provided herein are within the scope of the present invention. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may, but need not, have an altered structure or function. Alleles may be identified using standard techniques (such as hybridization, amplification and/or database sequence comparison).

Polynucleotides may be prepared using any of a variety of techniques. For example, an ovarian carcinoma polynucleotide may be identified, as described in more detail below, by screening a late passage ovarian tumor expression library with antisera generated against sera of immunocompetent mice after injection of such mice with sera from SCID mice implanted with late passage ovarian tumors. Ovarian carcinoma polynucleotides may also be identified using any of a variety of techniques designed to evaluate differential gene expression. Alternatively, polynucleotides may be amplified from cDNA prepared from ovarian tumor cells. Such polynucleotides may be amplified via polymerase chain reaction (PCR). For this approach, sequence-specific primers may be designed based on the sequences provided herein, and may be purchased or synthesized.

An amplified portion may be used to isolate a full length gene from a suitable library (e.g., an ovarian carcinoma cDNA library) using well known techniques. Within such techniques, a library (cDNA or genomic) is screened using one or more polynucleotide probes or primers suitable for amplification. Preferably, a library is size-selected to include larger molecules. Random primed libraries may also be preferred for identifying 5′ and upstream regions of genes. Genomic libraries are preferred for obtaining introns and extending 5′ sequences.

For hybridization techniques, a partial sequence may be labeled (e.g., by nick-translation or end-labeling with 32 P) using well known techniques. A bacterial or bacteriophage library is then screened by hybridizing filters containing denatured bacterial colonies (or lawns containing phage plaques) with the labeled probe (see Sambrook et al., Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratories, Cold Spring Harbor, N.Y., 1989). Hybridizing colonies or plaques are selected and expanded, and the DNA is isolated for further analysis. cDNA clones may be analyzed to determine the amount of additional sequence by, for example, PCR using a primer from the partial sequence and a primer from the vector. Restriction maps and partial sequences may be generated to identify one or more overlapping clones. The complete sequence may then be determined using standard techniques, which may involve generating a series of deletion clones. The resulting overlapping sequences are then assembled into a single contiguous sequence. A full length cDNA molecule can be generated by ligating suitable fragments, using well known techniques.

Alternatively, there are numerous amplification techniques for obtaining a full length coding sequence from a partial cDNA sequence. Within such techniques, amplification is generally performed via PCR. Any of a variety of commercially available kits may be used to perform the amplification step. Primers may be designed using, for example, software well known in the art. Primers are preferably 22-30 nucleotides in length, have a GC content of at least 50% and anneal to the target sequence at temperatures of about 68° C. to 72° C. The amplified region may be sequenced as described above, and overlapping sequences assembled into a contiguous sequence.

One such amplification technique is inverse PCR (see Triglia et al., Nucl. Acids Res . 16:8186, 1988), which uses restriction enzymes to generate a fragment in the known region of the gene. The fragment is then circularized by intramolecular ligation and used as a template for PCR with divergent primers derived from the known region. Within an alternative approach, sequences adjacent to a partial sequence may be retrieved by amplification with a primer to a linker sequence and a primer specific to a known region. The amplified sequences are typically subjected to a second round of amplification with the same linker primer and a second primer specific to the known region. A variation on this procedure, which employs two primers that initiate extension in opposite directions from the known sequence, is described in WO 96/38591. Additional techniques include capture PCR (Lagerstrom et al., PCR Methods Applic . 1:111-19, 1991) and walking PCR (Parker et al., Nucl. Acids. Res . 19:3055-60, 1991). Other methods employing amplification may also be employed to obtain a full length cDNA sequence.

In certain instances, it is possible to obtain a full length cDNA sequence by analysis of sequences provided in an expressed sequence tag (EST) database, such as that available from GenBank. Searches for overlapping ESTs may generally be performed using well known programs (e.g., NCBI BLAST searches), and such ESTs may be used to generate a contiguous full length sequence.

Certain nucleic acid sequences of cDNA molecules encoding portions of ovarian carcinoma antigens are provided in FIGS. 1A-1S (SEQ ID NOS:1 to 71) and FIGS. 15A to 15 E- 2 (SEQ ID NOs:82 to 310). The sequences provided in FIGS. 1A-1S appear to be novel. For sequences in FIGS. 15 A- 15 E- 2 , database searches revealed matches having substantial identity. These polynucleotides were isolated by serological screening of an ovarian tumor cDNA expression library, using a technique designed to identify secreted tumor antigens. Briefly, a late passage ovarian tumor expression library was prepared from a SCID-derived human ovarian tumor (OV9334) in the vector λ-screen (Novagen). The sera used for screening were obtained by injecting immunocompetent mice with sera from SCID mice implanted with one late passage ovarian tumors. This technique permits the identification of cDNA molecules that encode immunogenic portions of secreted tumor antigens.

The polynucleotides recited herein, as well as full length polynucleotides comprising such sequences, other portions of such full length polynucleotides, and sequences complementary to all or a portion of such full length molecules, are specifically encompassed by the present invention. It will be apparent to those of ordinary skill in the art that this technique can also be applied to the identification of antigens that are secreted from other types of tumors.

Other nucleic acid sequences of cDNA molecules encoding portions of ovarian carcinoma proteins are provided in FIGS. 4-9 (SEQ ID NOs:75-81), as well as SEQ ID NOs:313-384. These sequences were identified by screening a microarray of cDNAs for tumor-associated expression (i.e., expression that is at least five fold greater in an ovarian tumor than in normal ovarian tissue, as determined using a representative assay provided herein). Such screens were performed using a Synteni microarray (Palo Alto, Calif.) according to the manufacturer's instructions (and essentially as described by Schena et al., Proc. Natl. Acad. Sci. USA 93:10614-10619, 1996 and Heller et al., Proc. Natl. Acad. Sci. USA 94:2150-2155, 1997). SEQ ID NOs:311 and 391 provide full length sequences incorporating certain of these nucleic acid sequences.

Any of a variety of well known techniques may be used to evaluate tumor-associated expression of a cDNA. For example, hybridization techniques using labeled polynucleotide probes may be employed. Alternatively, or in addition, amplification techniques such as real-time PCR may be used (see Gibson et al., Genome Research 6:995-1001, 1996; Heid et al., Genome Research 6:986-994, 1996). Real-time PCR is a technique that evaluates the level of PCR product accumulation during amplification. This technique permits quantitative evaluation of mRNA levels in multiple samples. Briefly, mRNA is extracted from tumor and normal tissue and cDNA is prepared using standard techniques. Real-time PCR may be performed, for example, using a Perkin Elmer/Applied Biosystems (Foster City, Calif.) 7700 Prism instrument. Matching primers and fluorescent probes may be designed for genes of interest using, for example, the primer express program provided by Perkin Elmer/Applied Biosystems (Foster City, Calif.). Optimal concentrations of primers and probes may be initially determined by those of ordinary skill in the art, and control (e.g., β-actin) primers and probes may be obtained commercially from, for example, Perkin Elmer/Applied Biosystems (Foster City, Calif.). To quantitate the amount of specific RNA in a sample, a standard curve is generated alongside using a plasmid containing the gene of interest. Standard curves may be generated using the Ct values determined in the real-time PCR, which are related to the initial cDNA concentration used in the assay. Standard dilutions ranging from 10-10 6 copies of the gene of interest are generally sufficient. In addition, a standard curve is generated for the control sequence. This permits standardization of initial RNA content of a tissue sample to the amount of control for comparison purposes.

Polynucleotide variants may generally be prepared by any method known in the art, including chemical synthesis by, for example, solid phase phosphoramidite chemical synthesis. Modifications in a polynucleotide sequence may also be introduced using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis (see Adelman et al., DNA 2:183, 1983). Alternatively, RNA molecules may be generated by in vitro or in vivo transcription of DNA sequences encoding an ovarian carcinoma antigen, or portion thereof, provided that the DNA is incorporated into a vector with a suitable RNA polymerase promoter (such as T7 or SP6). Certain portions may be used to prepare an encoded polypeptide, as described herein. In addition, or alternatively, a portion may be administered to a patient such that the encoded polypeptide is generated in vivo.

A portion of a sequence complementary to a coding sequence (i.e., an antisense polynucleotide) may also be used as a probe or to modulate gene expression. cDNA constructs that can be transcribed into antisense RNA may also be introduced into cells or tissues to facilitate the production of antisense RNA. An antisense polynucleotide may be used, as described herein, to inhibit expression of an ovarian carcinoma protein. Antisense technology can be used to control gene expression through triple-helix formation, which compromises the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors or regulatory molecules (see Gee et al., In Huber and Carr, Molecular and Immunologic Approaches , Futura Publishing Co. (Mt. Kisco, N.Y.; 1994). Alternatively, an antisense molecule may be designed to hybridize with a control region of a gene (e.g., promoter, enhancer or transcription initiation site), and block transcription of the gene; or to block translation by inhibiting binding of a transcript to ribosomes.

Any polynucleotide may be further modified to increase stability in vivo. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5′ and/or 3′ ends; the use of phosphorothioate or 2′ O-methyl rather than phosphodiesterase linkages in the backbone; and/or the inclusion of nontraditional bases such as inosine, queosine and wybutosine, as well as acetyl-methyl-, thio- and other modified forms of adenine, cytidine, guanine, thymine and uridine.

Nucleotide sequences as described herein may be joined to a variety of other nucleotide sequences using established recombinant DNA techniques. For example, a polynucleotide may be cloned into any of a variety of cloning vectors, including plasmids, phagemids, lambda phage derivatives and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors and sequencing vectors. In general, a vector will contain an origin of replication functional in at least one organism, convenient restriction endonuclease sites and one or more selectable markers. Other elements will depend upon the desired use, and will be apparent to those of ordinary skill in the art.

Within certain embodiments, polynucleotides may be formulated so as to permit entry into a cell of a mammal, and expression therein. Such formulations are particularly useful for therapeutic purposes, as described below. Those of ordinary skill in the art will appreciate that there are many ways to achieve expression of a polynucleotide in a target cell, and any suitable method may be employed. For example, a polynucleotide may be incorporated into a viral vector such as, but not limited to, adenovirus, adeno-associated virus, retrovirus, or vaccinia or other pox virus (e.g., avian pox virus). Techniques for incorporating DNA into such vectors are well known to those of ordinary skill in the art. A retroviral vector may additionally transfer or incorporate a gene for a selectable marker (to aid in the identification or selection of transduced cells) and/or a targeting moiety, such as a gene that encodes a ligand for a receptor on a specific target cell, to render the vector target specific. Targeting may also be accomplished using an antibody, by methods known to those of ordinary skill in the art.

Other formulations for therapeutic purposes include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. A preferred colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (i.e., an artificial membrane vesicle). The preparation and use of such systems is well known in the art.

Ovarian Carcinoma Polypeptides

Within the context of the present invention, polypeptides may comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof, as described herein. As noted above, certain ovarian carcinoma proteins are ovarian carcinoma antigens that are expressed by ovarian tumor cells and react detectably within an immunoassay (such as an ELISA) with antisera generated against serum from an immunodeficient animal implanted with an ovarian tumor. Other ovarian carcinoma proteins are encoded by ovarian carcinoma polynucleotides recited herein. Polypeptides as described herein may be of any length. Additional sequences derived from the native protein and/or heterologous sequences may be present, and such sequences may (but need not) possess further immunogenic or antigenic properties.

An “immunogenic portion,” as used herein is a portion of an antigen that is recognized (i.e., specifically bound) by a B-cell and/or T-cell surface antigen receptor. Such immunogenic portions generally comprise at least 5 amino acid residues, more preferably at least 10, and still more preferably at least 20 amino acid residues of an ovarian carcinoma protein or a variant thereof. Preferred immunogenic portions are encoded by cDNA molecules isolated as described herein. Further immunogenic portions may generally be identified using well known techniques, such as those summarized in Paul, Fundamental Immunology , 3rd ed., 243-247 (Raven Press, 1993) and references cited therein. Such techniques include screening polypeptides for the ability to react with ovarian carcinoma protein-specific antibodies, antisera and/or T-cell lines or clones. As used herein, antisera and antibodies are “ovarian carcinoma protein-specific” if they specifically bind to an ovarian carcinoma protein (i.e., they react with the ovarian carcinoma protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins). Such antisera, antibodies and T cells may be prepared as described herein, and using well known techniques. An immunogenic portion of a native ovarian carcinoma protein is a portion that reacts with such antisera, antibodies and/or T-cells at a level that is not substantially less than the reactivity of the full length polypeptide (e.g., in an ELISA and/or T-cell reactivity assay). Such immunogenic portions may react within such assays at a level that is similar to or greater than the reactivity of the full length protein. Such screens may generally be performed using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, Antibodies. A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. For example, a polypeptide may be immobilized on a solid support and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide. Unbound sera may then be removed and bound antibodies detected using, for example, 125 I-labeled Protein A.

As noted above, a composition may comprise a variant of a native ovarian carcinoma protein. A polypeptide “variant,” as used herein, is a polypeptide that differs from a native ovarian carcinoma protein in one or more substitutions, deletions, additions and/or insertions, such that the immunogenicity of the polypeptide is not substantially diminished. In other words, the ability of a variant to react with ovarian carcinoma protein-specific antisera may be enhanced or unchanged, relative to the native ovarian carcinoma protein, or may be diminished by less than 50%, and preferably less than 20%, relative to the native ovarian carcinoma protein. Such variants may generally be identified by modifying one of the above polypeptide sequences and evaluating the reactivity of the modified polypeptide with ovarian carcinoma protein-specific antibodies or antisera as described herein. Preferred variants include those in which one or more portions, such as an N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include variants in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) has been removed from the N- and/or C-terminal of the mature protein.

Polypeptide variants preferably exhibit at least about 70%, more preferably at least about 90% and most preferably at least about 95% identity to the native polypeptide. Preferably, a variant contains conservative substitutions. A “conservative substitution” is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include leucine, isoleucine and valine; glycine and alanine; asparagine and glutamine; and serine, threonine, phenylalanine and tyrosine. Other groups of amino acids that may represent conservative changes include: (1) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his. A variant may also, or alternatively, contain nonconservative changes. Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenicity, secondary structure and hydropathic nature of the polypeptide.

As noted above, polypeptides may comprise a signal (or leader) sequence at the N-terminal end of the protein which co-translationally or post-translationally directs transfer of the protein. The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

Polypeptides may be prepared using any of a variety of well known techniques. Recombinant polypeptides encoded by DNA sequences as described above may be readily prepared from the DNA sequences using any of a variety of expression vectors known to those of ordinary skill in the art. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli , yeast or a mammalian cell line such as COS or CHO. Supernatants from suitable host/vector systems which secrete recombinant protein or polypeptide into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant polypeptide.

Portions and other variants having fewer than about 100 amino acids, and generally fewer than about 50 amino acids, may also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifield, J. Am. Chem. Soc . 85:2149-2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Applied BioSystems, Inc. (Foster City, Calif.), and may be operated according to the manufacturer's instructions.

Within certain specific embodiments, a polypeptide may be a fusion protein that comprises multiple polypeptides as described herein, or that comprises one polypeptide as described herein and a known tumor antigen, such as an ovarian carcinoma protein or a variant of such a protein. A fusion partner may, for example, assist in providing T helper epitopes (an immunological fusion partner), preferably T helper epitopes recognized by humans, or may assist in expressing the protein (an expression enhancer) at higher yields than the native recombinant protein. Certain preferred fusion partners are both immunological and expression enhancing fusion partners. Other fusion partners may be selected so as to increase the solubility of the protein or to enable the protein to be targeted to desired intracellular compartments. Still further fusion partners include affinity tags, which facilitate purification of the protein.

Fusion proteins may generally be prepared using standard techniques, including chemical conjugation. Preferably, a fusion protein is expressed as a recombinant protein, allowing the production of increased levels, relative to a non-fused protein, in an expression system. Briefly, DNA sequences encoding the polypeptide components may be assembled separately, and ligated into an appropriate expression vector. The 3′ end of the DNA sequence encoding one polypeptide component is ligated, with or without a peptide linker, to the 5′ end of a DNA sequence encoding the second polypeptide component so that the reading frames of the sequences are in phase. This permits translation into a single fusion protein that retains the biological activity of both component polypeptides.

A peptide linker sequence may be employed to separate the first and the second polypeptide components by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39-46, 1985; Murphy et al., Proc. Natl. Acad. Sci. USA 83:8258-8262, 1986; U.S. Pat. No. 4,935,233 and U.S. Pat. No. 4,751,180. The linker sequence may generally be from 1 to about 50 amino acids in length. Linker sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric interference.

The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5′ to the DNA sequence encoding the first polypeptides. Similarly, stop codons required to end translation and transcription termination signals are only present 3′ to the DNA sequence encoding the second polypeptide.

Fusion proteins are also provided that comprise a polypeptide of the present invention together with an unrelated immunogenic protein. Preferably the immunogenic protein is capable of eliciting a recall response. Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, for example, Stoute et al. New Engl. J. Med ., 336:86-91, 1997).

Within preferred embodiments, an immunological fusion partner is derived from protein D, a surface protein of the gram-negative bacterium Haemophilus influenza B (WO 91/18926). Preferably, a protein D derivative comprises approximately the first third of the protein (e.g., the first N-terminal 100-110 amino acids), and a protein D derivative may be lipidated. Within certain preferred embodiments, the first 109 residues of a Lipoprotein D fusion partner is included on the N-terminus to provide the polypeptide with additional exogenous T-cell epitopes and to increase the expression level in E. coli (thus functioning as an expression enhancer). The lipid tail ensures optimal presentation of the antigen to antigen present cells. Other fusion partners include the non-structural protein from influenzae virus, NS1 (hemaglutinin). Typically, the N-terminal 81 amino acids are used, although different fragments that include T-helper epitopes may be used.

In another embodiment, the immunological fusion partner is the protein known as LYTA, or a portion thereof (preferably a C-terminal portion). LYTA is derived from Streptococcus pneumoniae , which synthesizes an N-acetyl-L-alanine amidase known as amidase LYTA (encoded by the LytA gene; Gene 43:265-292, 1986). LYTA is an autolysin that specifically degrades certain bonds in the peptidoglycan backbone. The C-terminal domain of the LYTA protein is responsible for the affinity to the choline or to some choline analogues such as DEAE. This property has been exploited for the development of E. coli C-LYTA expressing plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing the C-LYTA fragment at the amino terminus has been described (see Biotechnology 10:795-798, 1992). Within a preferred embodiment, a repeat portion of LYTA may be incorporated into a fusion protein. A repeat portion is found in the C-terminal region starting at residue 178. A particularly preferred repeat portion incorporates residues 188-305.

In general, polypeptides (including fusion proteins) and polynucleotides as described herein are isolated. An “isolated” polypeptide or polynucleotide is one that is removed from its original environment. For example, a naturally-occurring protein is isolated if it is separated from some or all of the coexisting materials in the natural system. Preferably, such polypeptides are at least about 90% pure, more preferably at least about 95% pure and most preferably at least about 99% pure. A polynucleotide is considered to be isolated if, for example, it is cloned into a vector that is not a part of the natural environment.

Binding Agents

The present invention further provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to an ovarian carcinoma protein. As used herein, an antibody, or antigen-binding fragment thereof, is said to “specifically bind” to an ovarian carcinoma protein if it reacts at a detectable level (within, for example, an ELISA) with an ovarian carcinoma protein, and does not react detectably with unrelated proteins under similar conditions. As used herein, “binding” refers to a noncovalent association between two separate molecules such that a “complex” is formed. The ability to bind may be evaluated by, for example, determining a binding constant for the formation of the complex. The binding constant is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compounds are said to “bind,” in the context of the present invention, when the binding constant for complex formation exceeds about 10 3 L/mol. The binding constant maybe determined using methods well known in the art.

Binding agents may be further capable of differentiating between patients with and without a cancer, such as ovarian cancer, using the representative assays provided herein. In other words, antibodies or other binding agents that bind to a ovarian carcinoma antigen will generate a signal indicating the presence of a cancer in at least about 20% of patients with the disease, and will generate a negative signal indicating the absence of the disease in at least about 90% of individuals without the cancer. To determine whether a binding agent satisfies this requirement, biological samples (e.g., blood, sera, leukophoresis, urine and/or tumor biopsies) from patients with and without a cancer (as determined using standard clinical tests) may be assayed as described herein for the presence of polypeptides that bind to the binding agent. It will be apparent that a statistically significant number of samples with and without the disease should be assayed. Each binding agent should satisfy the above criteria; however, those of ordinary skill in the art will recognize that binding agents may be used in combination to improve sensitivity.

Any agent that satisfies the above requirements may be a binding agent. For example, a binding agent may be a ribosome, with or without a peptide component, an RNA molecule or a polypeptide. In a preferred embodiment, a binding agent is an antibody or an antigen-binding fragment thereof. Antibodies may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, e.g., Harlow and Lane, Antibodies. A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the generation of monoclonal antibodies as described herein, or via transfection of antibody genes into suitable bacterial or mammalian cell hosts, in order to allow for the production of recombinant antibodies. In one technique, an immunogen comprising the polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep or goats). In this step, the polypeptides of this invention may serve as the immunogen without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for an antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J. Immunol . 6:511-519, 1976, and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and their culture supernatants tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.

Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Within certain embodiments, the use of antigen-binding fragments of antibodies may be preferred. Such fragments include Fab fragments, which may be prepared using standard techniques. Briefly, immunoglobulins may be purified from rabbit serum by affinity chromatography on Protein A bead columns (Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988) and digested by papain to yield Fab and Fc fragments. The Fab and Fc fragments may be separated by affinity chromatography on protein A bead columns.

Monoclonal antibodies of the present invention may be coupled to one or more therapeutic agents. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins, and derivatives thereof Preferred radionuclides include 90 Y, 123 I, 125 I, 131 I, 186 Re, 188 Re, 211At, and 212 Bi. Preferred drugs include methotrexate, and pyrimidine and purine analogs. Preferred differentiation inducers include phorbol esters and butyric acid. Preferred toxins include ricin, abrin, diptheria toxin, cholera toxin, gelonin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.

A therapeutic agent may be coupled (e.g., covalently bonded) to a suitable monoclonal antibody either directly or indirectly (e.g., via a linker group). A direct reaction between an agent and an antibody is possible when each possesses a substituent capable of reacting with the other. For example, a nucleophilic group, such as an amino or sulfhydryl group, on one may be capable of reacting with a carbonyl-containing group, such as an anhydride or an acid halide, or with an alkyl group containing a good leaving group (e.g., a halide) on the other.

Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group. A linker group can function as a spacer to distance an antibody from an agent in order to avoid interference with binding capabilities. A linker group can also serve to increase the chemical reactivity of a substituent on an agent or an antibody, and thus increase the coupling efficiency. An increase in chemical reactivity may also facilitate the use of agents, or functional groups on agents, which otherwise would not be possible.

It will be evident to those skilled in the art that a variety of bifunctional or polyfunctional reagents, both homo- and hetero-functional (such as those described in the catalog of the Pierce Chemical Co., Rockford, Ill.), may be employed as the linker group. Coupling may be effected, for example, through amino groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such methodology, e.g., U.S. Pat. No. 4,671,958, to Rodwell et al.

Where a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group which is cleavable during or upon internalization into a cell. A number of different cleavable linker groups have been described. The mechanisms for the intracellular release of an agent from these linker groups include cleavage by reduction of a disulfide bond (e.g., U.S. Pat. No. 4,489,710, to Spitler), by irradiation of a photolabile bond (e.g., U.S. Pat. No. 4,625,014, to Senter et al.), by hydrolysis of derivatized amino acid side chains (e.g., U.S. Pat. No. 4,638,045, to Kohn et al.), by serum complement-mediated hydrolysis (e.g., U.S. Pat. No. 4,671,958, to Rodwell et al.), and acid-catalyzed hydrolysis (e.g., U.S. Pat. No. 4,569,789, to Blattler et al.).

It may be desirable to couple more than one agent to an antibody. In one embodiment, multiple molecules of an agent are coupled to one antibody molecule. In another embodiment, more than one type of agent may be coupled to one antibody. Regardless of the particular embodiment, immunoconjugates with more than one agent may be prepared in a variety of ways. For example, more than one agent may be coupled directly to an antibody molecule, or linkers which provide multiple sites for attachment can be used. Alternatively, a carrier can be used.

A carrier may bear the agents in a variety of ways, including covalent bonding either directly or via a linker group. Suitable carriers include proteins such as albumins (e.g., U.S. Pat. No. 4,507,234, to Kato et al.), peptides and polysaccharides such as aminodextran (e.g., U.S. Pat. No. 4,699,784, to Shih et al.). A carrier may also bear an agent by noncovalent bonding or by encapsulation, such as within a liposome vesicle (e.g., U.S. Pat. Nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. Pat. No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A radionuclide chelate may be formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms for binding the metal, or metal oxide, radionuclide. For example, U.S. Pat. No. 4,673,562, to Davison et al. discloses representative chelating compounds and their synthesis.

A variety of routes of administration for the antibodies and immunoconjugates may be used. Typically, administration will be intravenous, intramuscular, subcutaneous or in the bed of a resected tumor. It will be evident that the precise dose of the antibody/immunoconjugate will vary depending upon the antibody used, the antigen density on the tumor, and the rate of clearance of the antibody.

Also provided herein are anti-idiotypic antibodies that mimic an immunogenic portion of an ovarian carcinoma protein. Such antibodies may be raised against an antibody, or antigen-binding fragment thereof, that specifically binds to an immunogenic portion of an ovarian carcinoma protein, using well known techniques. Anti-idiotypic antibodies that mimic an immunogenic portion of an ovarian carcinoma protein are those antibodies that bind to an antibody, or antigen-binding fragment thereof, that specifically binds to an immunogenic portion of an ovarian carcinoma protein, as described herein.

T Cells

Immunotherapeutic compositions may also, or alternatively, comprise T cells specific for an ovarian carcinoma protein. Such cells may generally be prepared in vitro or ex vivo, using standard procedures. For example, T cells may be present within (or isolated from) bone marrow, peripheral blood or a fraction of bone marrow or peripheral blood of a mammal, such as a patient, using a commercially available cell separation system, such as the CEPRATE™ system, available from CellPro Inc., Bothell Wash. (see also U.S. Pat. No. 5,240,856; U.S. Pat. No. 5,215,926; WO 89/06280; WO 91/16116 and WO 92/07243). Alternatively, T cells may be derived from related or unrelated humans, non-human animals, cell lines or cultures.

T cells may be stimulated with an ovarian carcinoma polypeptide, polynucleotide encoding an ovarian carcinoma polypeptide and/or an antigen presenting cell (APC) that expresses such a polypeptide. Such stimulation is performed under conditions and for a time sufficient to permit the generation of T cells that are specific for the polypeptide. Preferably, an ovarian carcinoma polypeptide or polynucleotide is present within a delivery vehicle, such as a microsphere, to facilitate the generation of specific T cells.

T cells are considered to be specific for an ovarian carcinoma polypeptide if the T cells kill target cells coated with an ovarian carcinoma polypeptide or expressing a gene encoding such a polypeptide. T cell specificity may be evaluated using any of a variety of standard techniques. For example, within a chromium release assay or proliferation assay, a stimulation index of more than two fold increase in lysis and/or proliferation, compared to negative controls, indicates T cell specificity. Such assays may be performed, for example, as described in Chen et al., Cancer Res . 54:1065-1070, 1994. Alternatively, detection of the proliferation of T cells may be accomplished by a variety of known techniques. For example, T cell proliferation can be detected by measuring an increased rate of DNA synthesis (e.g., by pulse-labeling cultures of T cells with tritiated thymidine and measuring the amount of tritiated thymidine incorporated into DNA). Contact with an ovarian carcinoma polypeptide (200 ng/ml-100 μg/ml, preferably 100 ng/ml-25 μg/ml) for 3-7 days should result in at least a two fold increase in proliferation of the T cells and/or contact as described above for 2-3 hours should result in activation of the T cells, as measured using standard cytokine assays in which a two fold increase in the level of cytokine release (e.g., TNF or IFN-γ) is indicative of T cell activation (see Coligan et al., Current Protocols in Immunology, vol. 1, Wiley Interscience (Greene 1998). T cells that have been activated in response to an ovarian carcinoma polypeptide, polynucleotide or ovarian carcinoma polypeptide-expressing APC may be CD4 + and/or CD8 + . Ovarian carcinoma polypeptide-specific T cells may be expanded using standard techniques. Within preferred embodiments, the T cells are derived from a patient or a related or unrelated donor and are administered to the patient following stimulation and expansion.

For therapeutic purposes, CD4 + or CD8 + T cells that proliferate in response to an ovarian carcinoma polypeptide, polynucleotide or APC can be expanded in number either in vitro or in vivo. Proliferation of such T cells in vitro may be accomplished in a variety of ways. For example, the T cells can be re-exposed to an ovarian carcinoma polypeptide, with or without the addition of T cell growth factors, such as interleukin-2, and/or stimulator cells that synthesize an ovarian carcinoma polypeptide. Alternatively, one or more T cells that proliferate in the presence of an ovarian carcinoma polypeptide can be expanded in number by cloning. Methods for cloning cells are well known in the art, and include limiting dilution. Following expansion, the cells may be administered back to the patient as described, for example, by Chang et al., Crit. Rev. Oncol. Hematol . 22:213, 1996.

Pharmaceutical Compositions and Vaccines

Within certain aspects, polypeptides, polynucleotides, binding agents and/or immune system cells as described herein may be incorporated into pharmaceutical compositions or vaccines. Pharmaceutical compositions comprise one or more such compounds or cells and a physiologically acceptable carrier. Vaccines may comprise one or more such compounds or cells and a non-specific immune response enhancer. A non-specific immune response enhancer may be any substance that enhances an immune response to an exogenous antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactic galactide) and liposomes (into which the compound is incorporated; see e.g., Fullerton, U.S. Pat. No. 4,235,877). Vaccine preparation is generally described in, for example, M. F. Powell and M. J. Newman, eds., “Vaccine Design (the subunit and adjuvant approach),” Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other tumor antigens may be present, either incorporated into a fusion polypeptide or as a separate compound within the composition or vaccine.

A pharmaceutical composition or vaccine may contain DNA encoding one or more of the polypeptides as described above, such that the polypeptide is generated in situ. As noted above, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al., PNAS 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci . 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. Pat. No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., PNAS 91:215-219, 1994; Kass-Eisler et al., PNAS 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res . 73:1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be “naked,” as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. Compositions of the present invention may be formulated for any appropriate manner of administration, including for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres (e.g., polylactate polyglycolate) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. Nos. 4,897,268 and 5,075,109.

Such compositions may also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide) and/or preservatives. Alternatively, compositions of the present invention may be formulated as a lyophilizate. Compounds may also be encapsulated within liposomes using well known technology.

Any of a variety of non-specific immune response enhancers may be employed in the vaccines of this invention. For example, an adjuvant may be included. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.), Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N.J.), alum, biodegradable microspheres, monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, may also be used as adjuvants.

Within the vaccines provided herein, the adjuvant composition is preferably designed to induce an immune response predominantly of the Th1 type. High levels of Th1-type cytokines (e.g., IFN-γ, IL-2 and IL-12) tend to favor the induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10 and TNF-β) tend to favor the induction of humoral immune responses. Following application of a vaccine as provided herein, a patient will support an immune response that includes Th1- and Th2-type responses. Within a preferred embodiment, in which a response is predominantly Th1-type, the level of Th1-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffman, Ann. Rev. Immunol . 7:145-173, 1989.

Preferred adjuvants for use in eliciting a predominantly Th1-type response include, for example, a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A (3D-MPL), together with an aluminum salt. MPL adjuvants are available from Ribi ImmunoChem Research Inc. (Hamilton, Mont.; see U.S. Pat. Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). Also preferred is AS-2 (SmithKline Beecham). CpG-containing oligonucleotides (in which the CpG dinucleotide is unmethylated) also induce a predominantly Th1 response. Such oligonucleotides are well known and are described, for example, in WO 96/02555. Another preferred adjuvant is a saponin, preferably QS21, which may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO 96/33739. Other preferred formulations comprises an oil-in-water emulsion and tocopherol. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210. Any vaccine provided herein may be prepared using well known methods that result in a combination of antigen, immune response enhancer and a suitable carrier or excipient.

The compositions described herein may be administered as part of a sustained release formulation (i.e., a formulation such as a capsule or sponge that effects a slow release of compound following administration). Such formulations may generally be prepared using well known technology and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target site. Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane. Carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. The amount of active compound contained within a sustained release formulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented.

Any of a variety of delivery vehicles may be employed within pharmaceutical compositions and vaccines to facilitate production of an antigen-specific immune response that targets tumor cells. Delivery vehicles include antigen presenting cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that may be engineered to be efficient APCs. Such cells may, but need not, be genetically modified to increase the capacity for presenting the antigen, to improve activation and/or maintenance of the T cell response, to have anti-tumor effects per se and/or to be immunologically compatible with the receiver (i.e., matched HLA haplotype). APCs may generally be isolated from any of a variety of biological fluids and organs, including tumor and peritumoral tissues, and may be autologous, allogeneic, syngeneic or xenogeneic cells.

Certain preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen-presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392:245-251, 1998) and have been shown to be effective as a physiological adjuvant for eliciting prophylactic or therapeutic antitumor immunity (see Timmerman and Levy, Ann. Rev. Med . 50:507-529, 1999). In general, dendritic cells may be identified based on their typical shape (stellate in situ, with marked cytoplasmic processes (dendrites) visible in vitro) and based on the lack of differentiation markers of B cells (CD19 and CD20), T cells (CD3), monocytes (CD14) and natural killer cells (CD56), as determined using standard assays. Dendritic cells may, of course, be engineered to express specific cell-surface receptors or ligands that are not commonly found on dendritic cells in vivo or ex vivo, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, secreted vesicles antigen-loaded dendritic cells (called exosomes) may be used within a vaccine (see Zitvogel et al., Nature Med . 4:594-600, 1998).

Dendritic cells and progenitors may be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, peritumoral tissues-infiltrating cells, lymph nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells may be differentiated ex vivo by adding a combination of cytokines such as GM-CSF, IL-4, IL-13 and/or TNFα to cultures of monocytes harvested from peripheral blood. Alternatively, CD34 positive cells harvested from peripheral blood, umbilical cord blood or bone marrow may be differentiated into dendritic cells by adding to the culture medium combinations of GM-CSF, IL-3, TNFα, CD40 ligand, LPS, flt3 ligand and/or other compound(s) that induce maturation and proliferation of dendritic cells.

Dendritic cells are conveniently categorized as “immature” and “mature” cells, which allows a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of Fcγ receptor, mannose receptor and DEC-205 marker. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (e.g., CD54 and CD11) and costimulatory molecules (e.g., CD40, CD80 and CD86).

APCs may generally be transfected with a polynucleotide encoding a ovarian carcinoma antigen (or portion or other variant thereof) such that the antigen, or an immunogenic portion thereof, is expressed on the cell surface. Such transfection may take place ex vivo, and a composition or vaccine comprising such transfected cells may then be used for therapeutic purposes, as described herein. Alternatively, a gene delivery vehicle that targets a dendritic or other antigen presenting cell may be administered to a patient, resulting in transfection that occurs in vivo. In vivo and ex vivo transfection of dendritic cells, for example, may generally be performed using any methods known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al., Immunology and cell Biology 75:456-460, 1997. Antigen loading of dendritic cells may be achieved by incubating dendritic cells or progenitor cells with the polypeptide, DNA (naked or within a plasmid vector) or RNA; or with antigen-expressing recombinant bacterium or viruses (e.g., vaccinia, fowlpox, adenovirus or lentivirus vectors). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell help (e.g., a carrier molecule). Alternatively, a dendritic cell may be pulsed with a non-conjugated immunological partner, separately or in the presence of the polypeptide.

Cancer Therapy

In further aspects of the present invention, the compositions described herein may be used for immunotherapy of cancer, such as ovarian cancer. Within such methods, pharmaceutical compositions and vaccines are typically administered to a patient. As used herein, a “patient” refers to any warm-blooded animal, preferably a human. A patient may or may not be afflicted with cancer. Accordingly, the above pharmaceutical compositions and vaccines may be used to prevent the development of a cancer or to treat a patient afflicted with a cancer. Within certain preferred embodiments, a patient is afflicted with ovarian cancer. Such cancer may be diagnosed using criteria generally accepted in the art, including the presence of a malignant tumor. Pharmaceutical compositions and vaccines may be administered either prior to or following surgical removal of primary tumors and/or treatment such as administration of radiotherapy or conventional chemotherapeutic drugs.

Within certain embodiments, immunotherapy may be active immunotherapy, in which treatment relies on the in vivo stimulation of the endogenous host immune system to react against tumors with the administration of immuno response-modifying agents (such as tumor vaccines, bacterial adjuvants and/or cytokines).

Within other embodiments, immunotherapy may be passive immunotherapy, in which treatment involves the delivery of agents with established tumor-immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate antitumor effects and does not necessarily depend on an intact host immune system. Examples of effector cells include T lymphocytes (such as CD8 + cytotoxic T lymphocytes and CD4 + T-helper tumor-infiltrating lymphocytes), killer cells (such as Natural Killer cells and lymphokine-activated killer cells), B cells and antigen-presenting cells (such as dendritic cells and macrophages) expressing a polypeptide provided herein. T cell receptors and antibody receptors specific for the polypeptides recited herein may be cloned, expressed and transferred into other vectors or effector cells for adoptive immunotherapy. The polypeptides provided herein may also be used to generate antibodies or anti-idiotypic antibodies (as described above and in U.S. Pat. No. 4,918,164) for passive immunotherapy.

Effector cells may generally be obtained in sufficient quantities for adoptive immunotherapy by growth in vitro, as described herein. Culture conditions for expanding single antigen-specific effector cells to several billion in number with retention of antigen recognition in vivo are well known in the art. Such in vitro culture conditions typically use intermittent stimulation with antigen, often in the presence of cytokines (such as IL-2) and non-dividing feeder cells. As noted above, immunoreactive polypeptides as provided herein may be used to rapidly expand antigen-specific T cell cultures in order to generate a sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage or B cells, may be pulsed with immunoreactive polypeptides or transfected with one or more polynucleotides using standard techniques well known in the art. For example, antigen-presenting cells can be transfected with a polynucleotide having a promoter appropriate for increasing expression in a recombinant virus or other expression system. Cultured effector cells for use in therapy must be able to grow and distribute widely, and to survive long term in vivo. Studies have shown that cultured effector cells can be induced to grow in vivo and to survive long term in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al., Immunological Reviews 157: 177, 1997).

Alternatively, a vector expressing a polypeptide recited herein may be introduced into stem cells taken from a patient and clonally propagated in vitro for autologous transplant back into the same patient.

Routes and frequency of administration, as well as dosage, will vary from individual to individual, and may be readily established using standard techniques. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), intranasally (e.g., by aspiration), orally or in the bed of a resected tumor. Preferably, between 1 and 10 doses may be administered over a 52 week period. Preferably, 6 doses are administered, at intervals of 1 month, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of a compound that, when administered as described above, is capable of promoting an anti-tumor immune response, and is at least 10-50% above the basal (i.e., untreated) level. Such response can be monitored by measuring the anti-tumor antibodies in a patient or by vaccine-dependent generation of cytolytic effector cells capable of killing the patient's tumor cells in vitro. Such vaccines should also be capable of causing an immune response that leads to an improved clinical outcome (e.g., more frequent remissions, complete or partial or longer disease-free survival) in vaccinated patients as compared to non-vaccinated patients. In general, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in a dose ranges from about 100 μg to 5 mg per kg of host. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 mL to about 5 mL.

In general, an appropriate dosage and treatment regimen provides the active compound(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit. Such a response can be monitored by establishing an improved clinical outcome (e.g., more frequent remissions, complete or partial, or longer disease-free survival) in treated patients as compared to non-treated patients. Increases in preexisting immune responses to an ovarian carcinoma antigen generally correlate with an improved clinical outcome. Such immune responses may generally be evaluated using standard proliferation, cytotoxicity or cytokine assays, which may be performed using samples obtained from a patient before and after treatment.

Screens for Identifying Secreted Ovarian Carcinoma Antigens

The present invention provides methods for identifying secreted tumor antigens. Within such methods, tumors are implanted into immunodeficient animals such as SCID mice and maintained for a time sufficient to permit secretion of tumor antigens into serum. In general, tumors may be implanted subcutaneously or within the gonadal fat pad of an immunodeficient animal and maintained for 1-9 months, preferably 1-4 months. Implantation may generally be performed as described in WO 97/18300. The serum containing secreted antigens is then used to prepare antisera in immunocompetent mice, using standard techniques and as described herein. Briefly, 50-100 μL of sera (pooled from three sets of immunodeficient mice, each set bearing a different SCID-derived human ovarian tumor) may be mixed 1:1 (vol:vol) with an appropriate adjuvant, such as RIBI-MPL or MPL+TDM (Sigma Chemical Co., St. Louis, Mo.) and injected intraperitoneally into syngeneic immunocompetent animals at monthly intervals for a total of 5 months. Antisera from animals immunized in such a manner may be obtained by drawing blood after the third, fourth and fifth immunizations. The resulting antiserum is generally pre-cleared of E. coli and phage antigens and used (generally following dilution, such as 1:200) in a serological expression screen.

The library is typically an expression library containing cDNAs from one or more tumors of the type that was implanted into SCID mice. This expression library may be prepared in any suitable vector, such as λ-screen (Novagen). cDNAs that encode a polypeptide that reacts with the antiserum may be identified using standard techniques, and sequenced. Such cDNA molecules may be further characterized to evaluate expression in tumor and normal tissue, and to evaluate antigen secretion in patients.

The methods provided herein have advantages over other methods for tumor antigen discovery. In particular, all antigens identified by such methods should be secreted or released through necrosis of the tumor cells. Such antigens may be present on the surface of tumor cells for an amount of time sufficient to permit targeting and killing by the immune system, following vaccination.

Methods for Detecting Cancer

In general, a cancer may be detected in a patient based on the presence of one or more ovarian carcinoma proteins and/or polynucleotides encoding such proteins in a biological sample (such as blood, sera, urine and/or tumor biopsies) obtained from the patient. In other words, such proteins may be used as markers to indicate the presence or absence of a cancer such as ovarian cancer. In addition, such proteins may be useful for the detection of other cancers. The binding agents provided herein generally permit detection of the level of protein that binds to the agent in the biological sample. Polynucleotide primers and probes may be used to detect the level of mRNA encoding a tumor protein, which is also indicative of the presence or absence of a cancer. In general, an ovarian carcinoma-associated sequence should be present at a level that is at least three fold higher in tumor tissue than in normal tissue

There are a variety of assay formats known to those of ordinary skill in the art for using a binding agent to detect polypeptide markers in a sample. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. In general, the presence or absence of a cancer in a patient may be determined by (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting in the sample a level of polypeptide that binds to the binding agent; and (c) comparing the level of polypeptide with a predetermined cut-off value.

In a preferred embodiment, the assay involves the use of binding agent immobilized on a solid support to bind to and remove the polypeptide from the remainder of the sample. The bound polypeptide may then be detected using a detection reagent that contains a reporter group and specifically binds to the binding agent/polypeptide complex. Such detection reagents may comprise, for example, a binding agent that specifically binds to the polypeptide or an antibody or other agent that specifically binds to the binding agent, such as an anti-immunoglobulin, protein G, protein A or a lectin. Alternatively, a competitive assay may be utilized, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding agent after incubation of the binding agent with the sample. The extent to which components of the sample inhibit the binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use within such assays include full length ovarian carcinoma proteins and portions thereof to which the binding agent binds, as described above.

The solid support may be any material known to those of ordinary skill in the art to which the tumor protein may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Pat. No. 5,359,681. The binding agent may be immobilized on the solid support using a variety of techniques known to those of skill in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term “immobilization” refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the agent and functional groups on the support or may be a linkage by way of a cross-linking agent). Immobilization by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the binding agent, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and about 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of binding agent ranging from about 10 ng to about 10 μg, and preferably about 100 ng to about 1 μg, is sufficient to immobilize an adequate amount of binding agent.

Covalent attachment of binding agent to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the binding agent. For example, the binding agent may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).

In certain embodiments, the assay is a two-antibody sandwich assay. This assay may be performed by first contacting an antibody that has been immobilized on a solid support, commonly the well of a microtiter plate, with the sample, such that polypeptides within the sample are allowed to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complexes and a detection reagent (preferably a second antibody capable of binding to a different site on the polypeptide) containing a reporter group is added. The amount of detection reagent that remains bound to the solid support is then determined using a method appropriate for the specific reporter group.

More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked. Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin or Tween 20™ (Sigma Chemical Co., St. Louis, Mo.). The immobilized antibody is then incubated with the sample, and polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is a period of time that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with ovarian cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least about 95% of that achieved at equilibrium between bound and unbound polypeptide. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1% Tween 20™. The second antibody, which contains a reporter group, may then be added to the solid support. Preferred reporter groups include those groups recited above.

The detection reagent is then incubated with the immobilized antibody-polypeptide complex for an amount of time sufficient to detect the bound polypeptide. An appropriate amount of time may generally be determined by assaying the level of binding that occurs over a period of time. Unbound detection reagent is then removed and bound detection reagent is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products.

To determine the presence or absence of a cancer, such as ovarian cancer, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value for the detection of a cancer is the average mean signal obtained when the immobilized antibody is incubated with samples from patients without the cancer. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for the cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A Basic Science for Clinical Medicine , Little Brown and Co., 1985, p. 106-7. Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates (i.e., sensitivity) and false positive rates (100%-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand corner (i.e., the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive. Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for a cancer.

In a related embodiment, the assay is performed in a flow-through or strip test format, wherein the binding agent is immobilized on a membrane, such as nitrocellulose. In the flow-through test, polypeptides within the sample bind to the immobilized binding agent as the sample passes through the membrane. A second, labeled binding agent then binds to the binding agent-polypeptide complex as a solution containing the second binding agent flows through the membrane. The detection of bound second binding agent may then be performed as described above. In the strip test format, one end of the membrane to which binding agent is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing second binding agent and to the area of immobilized binding agent. Concentration of second binding agent at the area of immobilized antibody indicates the presence of a cancer. Typically, the concentration of second binding agent at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of binding agent immobilized on the membrane is selected to generate a visually discernible pattern when the biological sample contains a level of polypeptide that would be sufficient to generate a positive signal in the two-antibody sandwich assay, in the format discussed above. Preferred binding agents for use in such assays are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized on the membrane ranges from about 25 ng to about 1 μg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be performed with a very small amount of biological sample.

Of course, numerous other assay protocols exist that are suitable for use with the tumor proteins or binding agents of the present invention. The above descriptions are intended to be exemplary only. For example, it will be apparent to those of ordinary skill in the art that the above protocols may be readily modified to use ovarian carcinoma polypeptides to detect antibodies that bind to such polypeptides in a biological sample. The detection of such ovarian carcinoma protein specific antibodies may correlate with the presence of a cancer.

A cancer may also, or alternatively, be detected based on the presence of T cells that specifically react with an ovarian carcinoma protein in a biological sample. Within certain methods, a biological sample comprising CD4 + and/or CD8 + T cells isolated from a patient is incubated with an ovarian carcinoma protein, a polynucleotide encoding such a polypeptide and/or an APC that expresses at least an immunogenic portion of such a polypeptide, and the presence or absence of specific activation of the T cells is detected. Suitable biological samples include, but are not limited to, isolated T cells. For example, T cells may be isolated from a patient by routine techniques (such as by Ficoll/Hypaque density gradient centrifugation of peripheral blood lymphocytes). T cells may be incubated in vitro for 2-9 days (typically 4 days) at 37° C. with an ovarian carcinoma protein (e.g., 5-25 μg/ml). It may be desirable to incubate another aliquot of a T cell sample in the absence of ovarian carcinoma protein to serve as a control. For CD4 + T cells, activation is preferably detected by evaluating proliferation of the T cells. For CD8 + T cells, activation is preferably detected by evaluating cytolytic activity. A level of proliferation that is at least two fold greater and/or a level of cytolytic activity that is at least 20% greater than in disease-free patients indicates the presence of a cancer in the patient.

As noted above, a cancer may also, or alternatively, be detected based on the level of mRNA encoding an ovarian carcinoma protein in a biological sample. For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify a portion of an ovarian carcinoma protein cDNA derived from a biological sample, wherein at least one of the oligonucleotide primers is specific for (i.e., hybridizes to) a polynucleotide encoding the ovarian carcinoma protein. The amplified cDNA is then separated and detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a polynucleotide encoding an ovarian carcinoma protein may be used in a hybridization assay to detect the presence of polynucleotide encoding the tumor protein in a biological sample.

To permit hybridization under assay conditions, oligonucleotide primers and probes should comprise an oligonucleotide sequence that has at least about 60%, preferably at least about 75% and more preferably at least about 90%, identity to a portion of a polynucleotide encoding an ovarian carcinoma protein that is at least 10 nucleotides, and preferably at least 20 nucleotides, in length. Preferably, oligonucleotide primers and/or probes hybridize to a polynucleotide encoding a polypeptide described herein under moderately stringent conditions, as defined above. Oligonucleotide primers and/or probes which may be usefully employed in the diagnostic methods described herein preferably are at least 10-40 nucleotides in length. In a preferred embodiment, the oligonucleotide primers comprise at least 10 contiguous nucleotides, more preferably at least 15 contiguous nucleotides, of a DNA molecule having a sequence provided herein. Techniques for both PCR based assays and hybridization assays are well known in the art (see, for example, Mullis et al., Cold Spring Harbor Symp. Quant. Biol ., 51:263, 1987; Erlich ed., PCR Technology , Stockton Press, NY, 1989).

One preferred assay employs RT-PCR, in which PCR is applied in conjunction with reverse transcription. Typically, RNA is extracted from a biological sample such as a biopsy tissue and is reverse transcribed to produce cDNA molecules. PCR amplification using at least one specific primer generates a cDNA molecule, which may be separated and visualized using, for example, gel electrophoresis. Amplification may be performed on biological samples taken from a test patient and from an individual who is not afflicted with a cancer. The amplification reaction may be performed on several dilutions of cDNA spanning two orders of magnitude. A two-fold or greater increase in expression in several dilutions of the test patient sample as compared to the same dilutions of the non-cancerous sample is typically considered positive.

In another embodiment, ovarian carcinoma proteins and polynucleotides encoding such proteins may be used as markers for monitoring the progression of cancer. In this embodiment, assays as described above for the diagnosis of a cancer may be performed over time, and the change in the level of reactive polypeptide(s) evaluated. For example, the assays may be performed every 24-72 hours for a period of 6 months to 1 year, and thereafter performed as needed. In general, a cancer is progressing in those patients in whom the level of polypeptide detected by the binding agent increases over time. In contrast, the cancer is not progressing when the level of reactive polypeptide either remains constant or decreases with time.

Certain in vivo diagnostic assays may be performed directly on a tumor. One such assay involves contacting tumor cells with a binding agent. The bound binding agent may then be detected directly or indirectly via a reporter group. Such binding agents may also be used in histological applications. Alternatively, polynucleotide probes may be used within such applications.

As noted above, to improve sensitivity, multiple ovarian carcinoma protein markers may be assayed within a given sample. It will be apparent that binding agents specific for different proteins provided herein may be combined within a single assay. Further, multiple primers or probes may be used concurrently. The selection of tumor protein markers may be based on routine experiments to determine combinations that results in optimal sensitivity. In addition, or alternatively, assays for tumor proteins provided herein may be combined with assays for other known tumor antigens.

Diagnostic Kits

The present invention further provides kits for use within any of the above diagnostic methods. Such kits typically comprise two or more components necessary for performing a diagnostic assay. Components may be compounds, reagents, containers and/or equipment. For example, one container within a kit may contain a monoclonal antibody or fragment thereof that specifically binds to an ovarian carcinoma protein. Such antibodies or fragments may be provided attached to a support material, as described above. One or more additional containers may enclose elements, such as reagents or buffers, to be used in the assay. Such kits may also, or alternatively, contain a detection reagent as described above that contains a reporter group suitable for direct or indirect detection of antibody binding.

Alternatively, a kit may be designed to detect the level of mRNA encoding an ovarian carcinoma protein in a biological sample. Such kits generally comprise at least one oligonucleotide probe or primer, as described above, that hybridizes to a polynucleotide encoding an ovarian carcinoma protein. Such an oligonucleotide may be used, for example, within a PCR or hybridization assay. Additional components that may be present within such kits include a second oligonucleotide and/or a diagnostic reagent or container to facilitate the detection of a polynucleotide encoding an ovarian carcinoma protein.

The following Examples are offered by way of illustration and not by way of limitation.

SEQ ID NOs:1-71 are ovarian carcinoma antigen polynucleotides shown in FIGS. 1A-1S.

SEQ ID NOs:72-74 are ovarian carcinoma antigen polynucleotides shown in FIGS. 2A-2C.

SEQ ID NO:75 is the ovarian carcinoma polynucleotide 3g (FIG. 4 ).

SEQ ID NO:76 is the ovarian carcinoma polynucleotide 3f (FIG. 5 ).

SEQ ID NO:77 is the ovarian carcinoma polynucleotide 6b (FIG. 6 ).

SEQ ID NO:78 is the ovarian carcinoma polynucleotide 8e (FIG. 7 A).

SEQ ID NO:79 is the ovarian carcinoma polynucleotide 8h (FIG. 7 B).

SEQ ID NO:80 is the ovarian carcinoma polynucleotide 12e (FIG. 8 ).

SEQ ID NO:81 is the ovarian carcinoma polynucleotide 12h (FIG. 9 ).

SEQ ID NOs:82-310 are ovarian carcinoma antigen polynucleotides shown in FIGS. 15 A- 15 E- 2 .

SEQ ID NO:311 is a full length sequence of ovarian carcinoma polynucleotide O772P.

SEQ ID NO:312 is the O772P amino acid sequence.

SEQ ID NOs:313-384 are ovarian carcinoma antigen polynucleotides.

SEQ ID NOs:385-390 present sequences of O772P forms.

SEQ ID NO:391 is a full length sequence of ovarian carcinoma polynucleotide O8E.

SEQ ID NOs:392-393 are protein sequences encoded by O8E.

455

1

461

Homo sapien

1

ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt 60

tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg 120

catgatctca gctcgctgca acctccgcct cccacgttca agtgattctc ctgcctcagc 180

ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt 240

tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg 300

tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg 360

gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca 420

taactgacgt gactgccagc aagctcagtc actccgtggt c 461

2

540

Homo sapien

2

taggatgtgt tggaccctct gtgtcaaaaa aaacctcaca aagaatcccc tgctcattac 60

agaagaagat gcatttaaaa tatgggttat tttcaacttt ttatctgagg acaagtatcc 120

attaattatt gtgtcagaag agattgaata cctgcttaag aagcttacag aagctatggg 180

aggaggttgg cagcaagaac aatttgaaca ttataaaatc aactttgatg acagtaaaaa 240

tggcctttct gcatgggaac ttattgagct tattggaaat ggacagttta gcaaaggcat 300

ggaccggcag actgtgtcta tggcaattaa tgaagtcttt aatgaactta tattagatgt 360

gttaaagcag ggttacatga tgaaaaaggg ccacagacgg aaaaactgga ctgaaagatg 420

gtttgtacta aaacccaaca taatttctta ctatgtgagt gaggatctga aggataagaa 480

aggagacatt ctcttggatg aaaattgctg tgtagagtcc ttgcctgaca aagatggaaa 540

3

461

Homo sapien

3

ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt 60

tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg 120

catgatctca gctcgctgca acctccgcct cccacgttca agtgattctc ctgcctcagc 180

ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt 240

tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg 300

tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg 360

gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca 420

taactgacgt gactgccagc aagctcagtc actccgtggt c 461

4

tctttttctt tcgatttcct tcaatttgtc acgtttgatt ttatgaagtt gttcaagggc 60

taactgctgt gtattatagc tttctctgag ttccttcagc tgattgttaa atgaatccat 120

ttctgagagc ttagatgcag tttctttttc aagagcatct aattgttctt taagtctttg 180

gcataattct tccttttctg atgacttttt atgaagtaaa ctgatccctg aatcaggtgt 240

gttactgagc tgcatgtttt taattctttc gtttaatagc tgcttctcag ggaccagata 300

gataagctta ttttgatatt ccttaagctc ttgttgaagt tgtttgattt ccataatttc 360

caggtcacac tgtttatcca aaacttctag ctcagtcttt tgtgtttgct ttctgatttg 420

gacatcttgt agtctgcctg agatctgctg atgntttcca ttcactgctt ccagttccag 480

gtggagactt tnctttctgg agctcagcct gacaatgcct tcttgntccc t 531

5

531

Homo sapien

5

agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag 60

cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata 120

aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt 180

ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc 240

tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt 300

taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta 360

tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc 420

atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga 480

ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt a 531

6

531

Homo sapien

6

aatagattta atgcagagtg tcaacttcaa ttgattgata gtggctgcct agagtgctgt 60

gttgagtagg tttctgagga tgcaccctgg cttgaagaga aagactggca ggattaacaa 120

tatctaaaat ctcacttgta ggagaaacca caggcaccag agctgccact ggtgctggca 180

ccagctccac caaggccagc gaagagccca aatgtgagag tggcggtcag gctggcacca 240

gcactgaagc caccactggt gctggcactg gcactggcac tgttattggt actggtactg 300

gcaccagtgc tggcactgcc actctcttgg gctttggctt tagcttctgc tcccgcctgg 360

atccgggctt tggcccaggg tccgatatca gcttcgtccc agttgcaggg cccggcagca 420

ttctccgagc cgagcccaat gcccattcga gctctaatct cggccctagc cttggcttca 480

gctgcagcct cagctgcagc cttcaaatcc gcttccatcg cctctcggta c 531

7

531

Homo sapien

7

gccaagaaag cccgaaaggt gaagcatctg gatggggaag aggatggcag cagtgatcag 60

agtcaggctt ctggaaccac aggtggccga agggtctcaa aggccctaat ggcctcaatg 120

gcccgcaggg cttcaagggg tcccatagcc ttttgggccc gcagggcatc aaggactcgg 180

ttggctgctt gggcccggag agccttgctc tccctgagat cacctaaagc ccgtaggggc 240

aaggctcgcc gtagagctgc caagctccag tcatcccaag agcctgaagc accaccacct 300

cgggatgtgg cccttttgca agggagggca aatgatttgg tgaagtacct tttggctaaa 360

gaccagacga agattcccat caagcgctcg gacatgctga aggacatcat caaagaatac 420

actgatgtgt accccgaaat cattgaacga gcaggctatt ccttggagaa ggtatttggg 480

attcaattga aggaaattga taagaatgac cacttgtaca ttcttctcag c 531

8

gaggtctcac tatgttgccc aggctgttct tgaactcctg ggatcaagca atccacccat 60

gttggtctcc aaaagtgctg ggatcatagg cgtgagccac ctcacccagc caccaatttt 120

caatcaggaa gactttttcc ttcttcaaga agtgaagggt ttccagagta tagctacact 180

attgcttgcc tgagggtgac tacaaaattg cttgctaaaa ggttaggatg ggtaaagaat 240

tagattttct gaatgcaaaa ataaaatgtg aactaatgaa ctttaggtaa tacatattca 300

taaaataatt attcacatat ttcctgattt atcacagaaa taatgtatga aatgctttga 360

gtttcttgga gtaaactcca ttactcatcc caagaaacca tattataagt atcactgata 420

ataagaacaa caggaccttg tcataaattc tggataagag aaatagtctc tgggtgtttg 480

ntcttaattg ataaaattta cttgtccatc ttttagttca gaatcacaaa a 531

9

aagcggaaat gagaaaggag ggaaaatcat gtggtattga gcggaaaact gctggatgac 60

agggctcagt cctgttggag aactctgggt ggtgctgtag aacagggcca ctcacagtgg 120

ggtgcacaga ccagcacggc tctgtgacct gtttgttaca ggtccatgat gaggtaaaca 180

atacactgag tataagggtt ggtttagaaa ctcttacagc aatttgacaa agtaatcttc 240

tgtgcagtga atctaagaaa aaaattgggg ctgtatttgt atgttccttt ttttcatttc 300

atgttctgag ttacctattt ttattgcatt ttacaaaagc atccttccat gaaggaccgg 360

aagttaaaaa caaagcaggt cctttatcac agcactgtcg tagaacacag ttcagagtta 420

tccacccaag gagccaggga gctgggctaa accaaagaat tttgcttttg gttaatcatc 480

aggtacttga gttggaattg ttttaatccc atcattacca ggctggangt g 531

10

861

Homo sapien

10

ccgcggctcc tgtccagacc ctgaccctcc ctcccaaggc tcaaccgtcc cccaacaacc 60

gccagccttg tactgatgtc ggctgcgaga gcctgtgctt aagtaagaat caggccttat 120

tggagacatt caagcaaagg ttggacaact acttttccag aacagaaagg aaactcatgc 180

atcagaaaag gtgactaata aaggtaccag aagaatatgg ctgcacaaat accagaatct 240

gatcagataa aacagtttaa ggaatttctg gggacctaca ataaacttac agagacctgc 300

tttttggact gtgttagaga cttcacaaca agagaagtaa aacctgaaga gaccacctgt 360

tcagaacatt gcttacagaa atatttaaaa atgacacaaa gaatatccat gagatttcag 420

gaatatcata ttcagcagaa tgaagccctg gcagccaaag caggactcct tggccaacca 480

cgatagagaa gtcctgatgg atgaactttt gatgaaagat tgccaacagc tgctttattg 540

gaaatgagga ctcatctgat agaatcccct gaaagcagta gccaccatgt tcaaccatct 600

gtcatgactg tttggcaaat ggaaaccgct ggagaaacaa aattgctatt taccaggaat 660

aatcacaata gaaggtctta ttgttcagtg aaataataag atgcaacatt tgttgaggcc 720

ttatgattca gcagcttggt cacttgatta gaaaaataaa ccattgtttc ttcaattgtg 780

actgttaatt ttaaagcaac ttatgtgttc gatcatgtat gagatagaaa aatttttatt 840

actcaaagta aaataaatgg a 861

11

541

Homo sapien

11

gaaaaaaaat ataaaacaca cttttgcgaa aacggtggcc ctaaaagagg aaaagaattt 60

caccaatata aatccaattt tatgaaaact gacaatttaa tccaagaatc acttttgtaa 120

atgaagctag caagtgatga tatgataaaa taaacgtgga ggaaataaaa acacaagact 180

tggcataaga tatatccact tttgatatta aacttgtgaa gcatattctt cgacaaattg 240

tgaaagcgtt cctgatcttg cttgttctcc atttcaaata aggaggcata tcacatccca 300

agagtaacag aaaaagaaaa aagacatttt tgcattttga gatgaaccaa agacacaaaa 360

caaaacgaac aaagtgtcat gtctaattct agcctctgaa ataaaccttg aacatctcct 420

acaaggcacc gtgatttttg taattctaac ctgaagaaat gtgatgactt ttgtggacat 480

gaaaatcaga tgagaaaact gtggtctttc caaagcctga actcccctga aaacctttgc 540

a 541

12

541

Homo sapien

12

ctgggatcat ttctcttgat gtcataaaag actcttcttc ttcctcttca tcctcttctt 60

catcctcttc tgtacagtgc tgccgggtac aacggctatc tttgtcttta tcctgagatg 120

aagatgatgc ttctgtttct cctaccataa ctgaagaaat ttcgctggaa gtcgtttgac 180

tggctgtttc tctgacttca ccttctttgt caaacctgag tctttttacc tcatgcccct 240

cagcttccac agcatcttca tctggatgtt tatttttcaa agggctcact gaggaaactt 300

ctgattcaga ggtcgaagag tcactgtgat ttttctcctc attttgctgc aaatttgcct 360

ctttgctgtc tgtgctctca ggcaacccat ttgttgtcat gggggctgac aaagaaacct 420

ttggtcgatt aagtggcctg ggtgtcccag gcccatttat attagacctc tcagtatagc 480

ttggtgaatt tccaggaaac ataacaccat tcattcgatt taaactattg gaattggttt 540

t 541

13

441

Homo sapien

13

gagggttggt ggtagcggct tggggaggtg ctcgctctgt cggtcttgct ctctcgcacg 60

cttcccccgg ctcccttcgt ttcccccccc cggtcgcctg cgtgccggag tgtgtgcgag 120

ggagggggag ggcgtcgggg gggtgggggg aggcgttccg gtccccaaga gacccgcgga 180

gggaggcgga ggctgtgagg gactccggga agccatggac gtcgagaggc tccaggaggc 240

gctgaaagat tttgagaaga gggggaaaaa ggaagtttgt cctgtcctgg atcagtttct 300

ttgtcatgta gccaagactg gagaaacaat gattcagtgg tcccaattta aaggctattt 360

tattttcaaa ctggagaaag tgatggatga tttcagaact tcagctcctg agccaagagg 420

tcctcccaac cctaatgtcg a 441

14

aagcaggcgg ctcccgcgct cgcagggccg tgccacctgc ccgcccgccc gctcgctcgc 60

tcgcccgccg cgccgcgctg ccgaccgcca gcatgctgcc gagagtgggc tgccccgcgc 120

tgccgntgcc g 131

15

692

Homo sapien

15

atctcttgta tgccaaatat ttaatataaa tctttgaaac aagttcagat gaaataaaaa 60

tcaaagtttg caaaaacgtg aagattaact taattgtcaa atattcctca ttgccccaaa 120

tcagtatttt ttttatttct atgcaaaagt atgccttcaa actgcttaaa tgatatatga 180

tatgatacac aaaccagttt tcaaatagta aagccagtca tcttgcaatt gtaagaaata 240

ggtaaaagat tataagacac cttacacaca cacacacaca cacacacgtg tgcacgccaa 300

tgacaaaaaa caatttggcc tctcctaaaa taagaacatg aagaccctta attgctgcca 360

ggagggaaca ctgtgtcacc cctccctaca atccaggtag tttcctttaa tccaatagca 420

aatctgggca tatttgagag gagtgattct gacagccacg ttgaaatcct gtggggaacc 480

attcatgtcc acccactggt gccctgaaaa aatgccaata atttttcgct cccacttctg 540

ctgctgtctc ttccacatcc tcacatagac cccagacccg ctggcccctg gctgggcatc 600

gcattgctgg tagagcaagt cataggtctc gtctttgacg tcacagaagc gatacaccaa 660

attgcctggt cggtcattgt cataaccaga ga 692

16

728

Homo sapien

16

cagacggggt ttcactatgt tggctaggct ggtcttgaac tcctgacttc aggtgatctg 60

cctgccttgg cctcccaaag tgctgggatt acaggcataa gccactgcgc ccggctgatc 120

tgatggtttc ataaggcttt tccccctttt gctcagcact tctccttcct gccgccatgt 180

gaagaaggac atgtttgctt ccccttccac cacgattgta agttgtttcc tgaggcctcc 240

ccggccatgc tgaactgtga gtcaattaaa cctctttcct ttataaatta tccagttttg 300

ggtatgtctt tattagtaga atgagaacag actaatacaa cccttaaagg agactgacgg 360

agaggattct tcctggatcc cagcacttcc tctgaatgct actgacattc ttcttgagga 420

ctttaaactg ggagatagaa aacagattcc atggctcagc agcctgagag cagggaggga 480

gccaagctat agatgacatg ggcagcctcc cctgaggcca ggtgtggccg aacctgggca 540

gtgctgccac ccaccccacc agggccaagt cctgtccttg gagagccaag cctcaatcac 600

tgctagcctc aagtgtcccc aagccacagt ggctaggggg actcagggaa cagttcccag 660

tctgccctac ttctcttacc tttacccctc atacctccaa agtagaccat gttcatgagg 720

tccaaagg 728

17

aagcgaggaa gccactgcgg ctcctggctg aaaagcggcg ccaggctcgg gaacagaggg 60

aacgcgaaga acaggagcgg aagctgcagg ctgaaaggga caagcgaatg cgagaggagc 120

agctggcccg ggaggctgaa gcccgggctg aacgtgaggc cgaggcgcgg agacgggagg 180

agcaggaggc tcgagagaag gcgcaggctg agcaggagga gcaggagcga ctgcagaagc 240

agaaagagga agccgaagcc cggtcccggg aagaagctga gcgccagcgc caggagcggg 300

aaaagcactt tcagaaggag gaacaggaga gacaagagcg aagaaagcgg ctggaggaga 360

taatgaagag gactcggaaa tcagaagccg ccgaaaccaa gaagcaggat gcaaaggaga 420

ccgcagctaa caattccggc ccagaccctt gtgaaagctg tagagactcg gccctctggg 480

cttccagaaa ggattctatt gcagaaagga aggagctngg ccccccangg a 531

18

ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa 60

agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat 120

cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc 180

tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc 240

attgtttgct cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta 300

gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg 360

ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga 420

tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtagccc 480

cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat 540

cacntgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt 600

ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt 660

tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac 720

ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt 780

ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa 840

atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg 900

agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca 960

tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt 1020

cctctacaat aaagtaacaa t 1041

19

1043

Homo sapien

19

ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa 60

agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat 120

cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc 180

tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc 240

attgtttgct cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta 300

gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg 360

ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga 420

tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtagccc 480

cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat 540

cacctgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt 600

ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt 660

tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac 720

ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt 780

ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa 840

atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg 900

agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca 960

tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt 1020

cctctacaat aaagtaacaa tta 1043

20

448

Homo sapien

20

ggacgacaag gccatggcga tatcggatcc gaattcaagc ctttggaatt aaataaacct 60

ggaacaggga aggtgaaagt tggagtgaga tgtcttccat atctatacct ttgtgcacag 120

ttgaatggga actgtttggg tttagggcat cttagagttg attgatggaa aaagcagaca 180

ggaactggtg ggaggtcaag tggggaagtt ggtgaatgtg gaataactta cctttgtgct 240

ccacttaaac cagatgtgtt gcagctttcc tgacatgcaa ggatctactt taattccaca 300

ctctcattaa taaattgaat aaaagggaat gttttggcac ctgatataat ctgccaggct 360

atgtgacagt aggaaggaat ggtttcccct aacaagccca atgcactggt ctgactttat 420

aaattattta ataaaatgaa ctattatc 448

21

411

Homo sapien

21

ggcagtgaca ttcaccatca tgggaaccac cttccctttt cttcaggatt ctctgtagtg 60

gaagagagca cccagtgttg ggctgaaaac atctgaaagt agggagaaga acctaaaata 120

atcagtatct cagagggctc taaggtgcca agaagtctca ctggacattt aagtgccaac 180

aaaggcatac tttcggaatc gccaagtcaa aactttctaa cttctgtctc tctcagagac 240

aagtgagact caagagtcta ctgctttagt ggcaactaca gaaaactggt gttacccaga 300

aaaacaggag caattagaaa tggttccaat atttcaaagc tccgcaaaca ggatgtgctt 360

tcctttgccc atttagggtt tcttctcttt cctttctctt tattaaccac t 411

22

tgcgctgaaa acaacggcct cctttactgt taaaatgcag ccacaggtgc ttagccgtgg 60

gcatctcaac caccagcctc tgtggggggc aggtgggcgt ccctgtgggc ctctgggccc 120

acgtccagcc tctgtcctct gccttccgtt cttcgacagt gttcccggca tccctggtca 180

cttggtactt ggcgtgggcc tcctgtgctg ctccagcagc tcctccaggn ggtcggcccg 240

cttcaccgca gcctcatgtt gtgtccggag gctgctcacg gcctcctcct tcctcgcgag 300

ggctgtcttc accctccggn gcacctcctc cagctccagc tgctggcggg cctgcagcgt 360

ggccagctcg gccttggcct gccgcgtctc ctcctcarag gctgccagcc ggtcctcgaa 420

ctcctggcgg atcacctggg ccaggttgct gcgctcgcta gaaagctgct cgttcaccgc 480

ctgcgcatcc tccagcgccc gctccttctg ccgcacaagg ccctgcagac gcagattctc 540

gccctcggcc tccccaagct ggcccttcag ctccgagcac cgctcctgaa gcttccgctc 600

cgactgctcc agctcggaga gctcggcctc gtacttgtcc cgtaagcgct tgatgcggct 660

ctcggcagcc ttctcactct cctccttggc cagcgccatg tcggcctcca gccggtgaat 720

gaccagctca atctccttgt cccggccttt ccggatttct tccctcagct cctgttcccg 780

gttcagcagc cacgcctcct ccttcctggt gcggccggcc tcccacgcct gcctctccag 840

ctccagctgc tgcttcaggg tattcagctc catctggcgg gcctgcagcg tggcca 896

23

111

Homo sapien

23

caacttatta cttgaaatta taatatagcc tgtccgtttg ctgtttccag gctgtgatat 60

attttcctag tggtttgact ttaaaaataa ataaggttta attttctccc c 111

24

tgcaagtcac gggagtttat ttatttaatt tttttcccca gatggagact ctgtcgccca 60

ggctggagtg caatggtgtg atcttggctc actgcaacct ccacctcctg ggttcaagcg 120

attctcctgc cacagcctcc cgagtagctg ggattacagg tgcccgccac cacacccagc 180

taatttttat atttttagta aagacagggt ttccccatgt tggccaggct ggtcttgaac 240

ttctgacctc aggtgatcca cctgcctcgg cctcccaaag tgttgggatt acaggcgtga 300

gctacccgtg cctggccagc cactggagtt taaaggacag tcatgttggc tccagcctaa 360

ggcggcattt tcccccatca gaaagcccgc ggctcctgta cctcaaaata gggcacctgt 420

aaagtcagtc agtgaagtct ctgctctaac tggccacccg gggccattgg cntctgacac 480

agccttgcca ggangcctgc atctgcaaaa gaaaagttca cttcctttcc g 531

25

cagagaatct kagaaagatg tcgcgttttc ttttaatgaa tgagagaagc ccatttgtat 60

ccctgaatca ttgagaaaag gcggcggtgg cgacagcggc gacctaggga tcgatctgga 120

gggacttggg gagcgtgcag agacctctag ctcgagcgcg agggacctcc cgccgggatg 180

cctggggagc agatggaccc tactggaagt cagttggatt cagatttctc tcagcaagat 240

actccttgcc tgataattga agattctcag cctgaaagcc aggttctaga ggatgattct 300

ggttctcact tcagtatgct atctcgacac cttcctaatc tccagacgca caaagaaaat 360

cctgtgttgg atgttgngtc caatccttga acaaacagct ggagaagaac gaggagaccg 420

gtaatagtgg gttcaatgaa catttgaaag aaaaccaggt tgcagaccct g 471

26

541

Homo sapien

26

gactgtcctg aacaagggac ctctgaccag agagctgcag gagatgcaga gtggtggcag 60

gagtggaagc caaagaacac ccaccttcct cccttgaagg agtagagcaa ccatcagaag 120

atactgtttt attgctctgg tcaaacaagt cttcctgagt tgacaaaacc tcaggctctg 180

gtgacttctg aatctgcagt ccactttcca taagttcttg tgcagacaac tgttcttttg 240

cttccatagc agcaacagat gctttggggc taaaaggcat gtcctctgac cttgcaggtg 300

gtggattttg ctcttttaca acatgtacat ccttactggg ctgtgctgtc acagggatgt 360

ccttgctgga ctgttctgct atggggatat cttcgttgga ctgttcttca tgcttaattg 420

cagtattagc atccacatca gacagcctgg tataaccaga gttggtggtt actgattgta 480

gctgctcttt gtccacttca tatggcacaa gtattttcct caacatcctg gctctgggaa 540

g 541

27

gaaatgtata tttaatcatt ctcttgaacg atcagaactc traaatcagt tttctataac 60

arcatgtaat acagtcaccg tggctccaag gtccaggaag gcagtggtta acacatgaag 120

agtgtgggaa gggggctgga aacaaagtat tcttttcctt caaagcttca ttcctcaagg 180

cctcaattca agcagtcatt gtccttgctt tcaaaagtct gtgtgtgctt catggaaggt 240

atatgtttgt tgccttaatt tgaattgtgg ccaggaaggg tctggagatc taaattcaga 300

gtaagaaaac ctgagctaga actcaggcat ttctcttaca gaacttggct tgcagggtag 360

aatgaangga aagaaactta gaagctcaac aagctgaaga taatcccatc aggcatttcc 420

cataggcctt gcaactctgt tcactgagag atgttatcct g 461

28

541

Homo sapien

28

agtctggagt gagcaaacaa gagcaagaaa caarragaag ccaaaagcag aaggctccaa 60

tatgaacaag ataaatctat cttcaaagac atattagaag ttgggaaaat aattcatgtg 120

aactagacaa gtgtgttaag agtgataagt aaaatgcacg tggagacaag tgcatcccca 180

gatctcaggg acctccccct gcctgtcacc tggggagtga gaggacagga tagtgcatgt 240

tctttgtctc tgaattttta gttatatgtg ctgtaatgtt gctctgagga agcccctgga 300

aagtctatcc caacatatcc acatcttata ttccacaaat taagctgtag tatgtaccct 360

aagacgctgc taattgactg ccacttcgca actcaggggc ggctgcattt tagtaatggg 420

tcaaatgatt cactttttat gatgcttccc aaggtgcctt ggcttctctt cccaactgac 480

aaatgcccaa gttgagaaaa atgatcataa ttttagcata aaccgagcaa tcggcgaccc 540

c 541

29

411

Homo sapien

29

tagctgtctt cctcactctt atggcaatga ccccatatct taatggatta agataatgaa 60

agtgtatttc ttacactctg tatctatcac cagaagctga ggtgatagcc cgcttgtcat 120

tgtcatccat attctgggac tcaggcggga actttctgga atattgccag ggagcatggc 180

agaggggcac agtgcattct gggggaatgc acattggctc agcctgggta atgagtgata 240

tacattacct ctgttcacaa ctcattgccc agcaccagtc acaaggcccc accaaatacc 300

agagcccaag aaatgtagtc ctgttgatat ggttttgctg tgtcccaacc caaatctcat 360

cttgaattgt aagctcccat aattcccatg tgttgtggga gggacctggt g 411

30

511

Homo sapien

30

atcatgagga tgttaccaaa gggatggtac taaaccattt gtattcgtct gttttcacac 60

tgctttgaag atactacctg agactgggta atttataaac aaaagagatt taattgactc 120

acagttctgc atggctgaag aggcctcagg aaacttacag tcatggtgga aggcaaagga 180

ggagcaaggc atgtcttaca tgtcagtagg agagagagcg agagcaggag aacctgccac 240

ttataaacca ttcagatctc ataactccct atcatgagaa aaacatggag gaaaccaccc 300

tcatgatcca atcacctccc gccaggtccc tccctcgaca cgtggggatt ataattcagg 360

attagaggga cacagagaca aaccatatca tcattcatga gaaatccacc ctcatagtcc 420

aatcagctcc taccaggccc cacctccaac actggggatt gcaattcaac atgagatttg 480

gatggggaca cagattcaaa ccatatcata c 511

31

827

Homo sapien

31

catggccttt ctccttagag gccagaggtg ctgccctggc tgggagtgaa gctccaggca 60

ctaccagctt tcctgatttt cccgtttggt ccatgtgaag agctaccacg agccccagcc 120

tcacagtgtc cactcaaggg cagcttggtc ctcttgtcct gcagaggcag gctggtgtga 180

ccctgggaac ttgacccggg aacaacaggt ggcccagagt gagtgtggcc tggcccctca 240

acctagtgtc cgtcctcctc tctcctggag ccagtcttga gtttaaaggc attaagtgtt 300

agatacaagc tccttgtggc tggaaaaaca cccctctgct gataaagctc agggggcact 360

gaggaagcag aggccccttg ggggtgccct cctgaagaga gcgtcaggcc atcagctctg 420

tccctctggt gctcccacgt ctgttcctca ccctccatct ctgggagcag ctgcacctga 480

ctggccacgc gggggcagtg gaggcacagg ctcagggtgg ccgggctacc tggcacccta 540

tggcttacaa agtagagttg gcccagtttc cttccacctg aggggagcac tctgactcct 600

aacagtcttc cttgccctgc catcatctgg ggtggctggc tgtcaagaaa ggccgggcat 660

gctttctaaa cacagccaca ggaggcttgt agggcatctt ccaggtgggg aaacagtctt 720

agataagtaa ggtgacttgc ctaaggcctc ccagcaccct tgatcttgga gtctcacagc 780

agactgcatg tsaacaactg gaaccgaaaa catgcctcag tataaaa 827

32

291

Homo sapien

32

ccagaacctc cttctctttg gagaatgggg aggcctcttg gagacacaga gggtttcacc 60

ttggatgacc tctagagaaa ttgcccaaga agcccacctt ctggtcccaa cctgcagacc 120

ccacagcagt cagttggtca ggccctgctg tagaaggtca cttggctcca ttgcctgctt 180

ccaaccaatg ggcaggagag aaggccttta tttctcgccc acccattctc ctgtaccagc 240

acctccgttt tcagtcagyg ttgtccagca acggtaccgt ttacacagtc a 291

33

491

Homo sapien

33

tgcatgtagt tttatttatg tgttttsgtc tggaaaacca agtgtcccag cagcatgact 60

gaacatcact cacttcccct acttgatcta caaggccaac gccgagagcc cagaccagga 120

ttccaaacac actgcacgag aatattgtgg atccgctgtc aggtaagtgt ccgtcactga 180

cccaracgct gttacgtggc acatgactgt acagtgccac gtaacagcac tgtacttttc 240

tcccatgaac agttacctgc catgtatcta catgattcag aacattttga acagttaatt 300

ctgacacttg aataatccca tcaaaaaccg taaaatcact ttgatgtttg taacgacaac 360

atagcatcac tttacgacag aatcatctgg aaaaacagaa caacgaatac atacatctta 420

aaaaatgctg gggtgggcca ggcacagctt cacgcctgta atcccagcac tttgggaggc 480

ttaagcgggt g 491

34

tggggcggaa agaagccaag gccaaggagc tggtgcggca gctgcagctg gaggccgagg 60

agcagaggaa gcagaagaag cggcagagtg tgtcgggcct gcacagatac cttcacttgc 120

tggatggaaa tgaaaattac ccgtgtcttg tggatgcaga cggtgatgtg atttccttcc 180

caccaataac caacagtgag aagacaaagg ttaagaaaac gacttctgat ttgtttttgg 240

aagtaacaag tgccaccagt ctgcagattt gcaaggatgt catggatgcc ctcattctga 300

aaatggcaag aaatgaaaaa gtacacttta gaaaataaag aggaaggatc actctcagat 360

actgaagccg atgcagtctc tggacaactt ccagatccca caacgaatcc cagtgctgga 420

aaggacgggc ccttccttct ggtggtggaa cangtcccgg tggtggatct tggaanggaa 480

cctgaangtg gtgtaccccg tccaaggccg accttggcca c 521

35

tcccgcgctc gcagggcncg tgccacctgc cygtccgccc gctcgctcgc tcgcccgccg 60

cgccgcgctg ccgaccgyca gcatgctgcc gagagtgggc tgccccgcgc tgccgctgcc 120

gccgccgccg ctgctgccgc tgctgccgct gctgctgctg c 161

36

341

Homo sapien

36

ggcgggtagg catggaactg agaagaacga agaagctttc agactacgtg gggaagaatg 60

aaaaaaccaa aattatcgcc aagattcagc aaaggggaca gggagctcca gcccgagagc 120

ctattattag cagtgaggag cagaagcagc tgatgctgta ctatcacaga agacaagagg 180

agctcaagag attggaagaa aatgatgatg atgcctattt aaactcacca tgggcggata 240

acactgcttt gaaaagacat tttcatggag tgaaagacat aaagtggaga ccaagatgaa 300

gttcaccagc tgatgacact tccaaagaga ttagctcacc t 341

37

tctgaaggtt aaatgtttca tctaaatagg gataatgrta aacacctata gcatagagtt 60

gtttgagatt aaatgagata atacatgtaa aattatgtgc ctggcataca gcaagattgt 120

tgttgttgtt gatgatgatg atgatgatga taatattttt ctatccccag tgcacaactg 180

cttgaaccta ttagataatc aatacatgtt tcttgaactg agatcaattt ccccatgttg 240

tctgactgat gaagccctac attttcttct agaggagatg acatttgagc aagatcttaa 300

agaaaatcag atgccttcac ctgaccactg cttggtgatc ccatggcact ttgtacatct 360

ctccattagc tctcatctca ccagcccatc attattgtat gtgctgcctt ctgaagcttg 420

cagctggcta ccatcmggta gaataaaaat catcctttca taaaatagtg accctccttt 480

tttatttgca tttcccaaag ccaagcaccg tggganggta g 521

38

461

Homo sapien

38

tatgaagaag ggaaaagaag ataatttgtg aaagaaatgg gtccagttac tagtctttga 60

aaagggtcag tctgtagctc ttcttaatga gaataggcag ctttcagttg ctcagggtca 120

gatttcctta gtggtgtatc taatcacagg aaacatctgt ggttccctcc agtctctttc 180

tgggggactt gggcccactt ctcatttcat ttaattagag gaaatagaac tcaaagtaca 240

atttactgtt gtttaacaat gccacaaaga catggttggg agctatttct tgatttgtgt 300

aaaatgctgt ttttgtgtgc tcataatggt tccaaaaatt gggtgctggc caaagagaga 360

tactgttaca gaagccagca agaagacctc tgttcattca cacccccggg gatatcagga 420

attgactcca gtgtgtgcaa atccagtttg gcctatcttc t 461

39

769

Homo sapien

39

tgagggactg attggtttgc tctctgctat tcaattcccc aagcccactt gttcctgcag 60

cgtcctcctt ctcattccct ttagttgtac cctctctttc atctgagacc tttccttctt 120

gatgtcgcct tttcttcttc ttgctttttc tgatgttctg ctcagcatgt tctgggtgct 180

tctcatctgc atcattcctt tcagatgctg tagcttcttc ctcctctttc tgcctccttt 240

tctttttctt ttttttgggg ggcttgctct ctgactgcag ttgaggggcc ccagggtcct 300

ggcctttgag acgagccagg aaggcctgct cctgggcctc taggcgagca agcttggcct 360

tcattgtgat cccaagacgg gcagccttgt gtgctgttcg cccctcacag gcttggagca 420

gcatctcatc agtcagaatc tttggggact tggacccctg gttgtcgtca tcactgcagc 480

tctccaagtc tttgtttggc ttctctccac ctgaagtcaa tgtagccatc ttcacaaact 540

tctgatacag caagttgggc ttgggatgat tataacgggt ggtctcctta gaaaggctcc 600

ttatctgtac tccatcctgc ccagtttcca ctaccaagtt ggccgcagtc ttgttgaaga 660

gctcattcca ccagtggttt gtgaactcct tggcagggtc atgtcctacc ccatgagtgt 720

cttgcttcag ygtcaccctg agagcctgag tgataccatt ctccttccg 769

40

292

Homo sapien

40

gacaacatga aataaatcct agaggacaaa attaaactca atagagtgta gtctagttaa 60

aaactcgaaa aatgagcaag tctggtggga gtggaggaag ggctatacta taaatccaag 120

tgggcctcct gatcttaaca agccatgctc attatacaca tctctgaact ggacatacca 180

cctttacgca ggaaacaggg cttggaactt ctaagggaaa ttaacatgca ccacccacat 240

ctaacctacc tgccgggtag gtaccatccc tgcttcgctg aaatcagtgc tc 292

41

406

Homo sapien

41

ttggaattaa ataaacctgg aacagggaag gtgaaagttg gagtgagatg tcttccatat 60

ctataccttt gtgcacagtt gaatgggaac tgtttgggtt tagggcatct tagagttgat 120

tgatggaaaa agcagacagg aactggtggg aggtcaagtg gggaagttgg tgaatgtgga 180

ataacttacc tttgtgctcc acttaaacca gatgtgttgc agctttcctg acatgcaagg 240

atctacttta attccacact ctcattaata aattgaataa aagggaatgt tttggcacct 300

gatataatct gccaggctat gtgacagtag gaaggaatgg tttcccctaa caagcccaat 360

gcactggtct gactttataa attatttaat aaaatgaact attatc 406

42

381

Homo sapien

42

aaactggacc tgcaacaggg acatgaattt actgcarggt ctgagcaagc tcagcccctc 60

tacctcaggg ccccacagcc atgactacct cccccaggag cgggagggtg aagggggcct 120

gtctctgcaa gtggagccag agtggaggaa tgagctctga agacacagca cccagccttc 180

tcgcaccagc caagccttaa ctgcctgcct gaccctgaac cagaacccag ctgaactgcc 240

cctccaaggg acaggaaggc tgggggaggg agtttacaac ccaagccatt ccaccccctc 300

ccctgctggg gagaatgaca catcaagctg ctaacaattg ggggaagggg aaggaagaaa 360

actctgaaaa caaaatcttg t 381

43

451

Homo sapien

43

catgcgtttc accactgttg gccaggctgg tctcgaactc ctggcctcaa gcaatccacc 60

cgcctcagcc tccaaaagtg ctgggattac agatgtgagc catggcacca tgccaaaagg 120

ctatattcct ggctctgtgt ttccgagact gcttttaatc ccaacttctc tacatttaga 180

ttaaaaaata ttttattcat ggtcaatctg gaacataatt actgcatctt aagtttccac 240

tgatgtatat agaaggctaa aggcacaatt tttatcaaat ctagtagagt aaccaaacat 300

aaaatcatta attactttca acttaataac taattgacat tcctcaaaag agctgttttc 360

aatcctgata ggttctttat tttttcaaaa tatatttgcc atgggatgct aatttgcaat 420

aaggcgcata atgagaatac cccaaactgg a 451

44

521

Homo sapien

44

gttggacccc cagggactgg aaagacactt cttgcccgag ctgtggcggg agaagctgat 60

gttccttttt attatgcttc tggatccgaa tttgatgaga tgtttgtggg tgtgggagcc 120

agccgtatca gaaatctttt tagggaagca aaggcgaatg ctccttgtgt tatatttatt 180

gatgaattag attctgttgg tgggaagaga attgaatctc caatgcatcc atattcaagg 240

cagaccataa atcaacttct tgctgaaatg gatggtttta aacccaatga aggagttatc 300

ataataggag ccacaaactt cccagaggca ttagataatg ccttaatacc gtcctggtcg 360

ttttgacatg caagttacag ttccaaggcc agatgtaaaa ggtcgaacag aaattttgaa 420

atggtatctc aataaaataa agtttgatca atcccgttga tccagaaatt atagcctcga 480

ggtactggtg gcttttccgg aagcagagtt gggagaatct t 521

45

585

Homo sapien

45

gcctacaaca tccagaaaga gtctaccctg cacctggtgc tscgtctcag aggtgggatg 60

cagatcttcg tgaagaccct gactggtaag accatcactc tcgaagtgga gccgagtgac 120

accatygaga acgtcaaagc aaagatccar gacaaggaag gcrtycctcc tgaccagcag 180

aggttgatct ttgccggaaa gcagctggaa gatggdcgca ccctgtctga ctacaacatc 240

cagaaagagt cyaccctgca cctggtgctc cgtctcagag gtgggatgca ratcttcgtg 300

aagaccctga ctggtaagac catcaccctc gaggtggagc ccagtgacac catcgagaat 360

gtcaaggcaa agatccaaga taaggaaggc atccctcctg atcagcagag gttgatcttt 420

gctgggaaac agctggaaga tggacgcacc ctgtctgact acaacatcca gaaagagtcc 480

actctgcact tggtcctgcg cttgaggggg ggtgtctaag tttccccttt taaggtttcm 540

acaaatttca ttgcactttc ctttcaataa agttgttgca ttccc 585

46

481

Homo sapien

46

gaactgggcc ctgagcccaa gtcatgcctt gtgtccgcat ctgccgtgtc acctctgtkc 60

ctgcccctca cccctccctc ctggtcttct gagccagcac catctccaaa tagcctattc 120

cttcctgcaa atcacacaca catgcgggcc acacatacct gctgccctgg agatggggaa 180

gtaggagaga tgaatagagg cccatacatt gtacagaagg aggggcaggt gcagataaaa 240

gcagcagacc cagcggcagc tgaggtgcat ggagcacggt tggggccggc attgggctga 300

gcacctgatg ggcctcatct cgtgaatcct cgaggcagcg ccacagcaga ggagttaagt 360

ggcacctggg ccgagcagag caggagactg agggtcagag tggaggctaa gctgccctgg 420

aactcctcaa tcttgcctgc cccctagtat gaagccccct tcctgcccct acaattcctg 480

a 481

47

atggatctta ctttgccacc caggttggag tgcagtgctg caatcttggc tcactgcagc 60

cttaacctcc caggctcaag ctatcctcct gccaaagcct tccacatagc tgggactaca 120

ggtacacngc caccacaccc agctaaaatt tttgtatttt ttgtagagac gggatctcgc 180

cacgttgccc aggctggtcc catcctgacc tcaagcagat ctgcccacct cagcccccca 240

acgtgctagg attacaggcg tgagccaccg cacccagcct ttgttttgct tttaatggaa 300

tcaccagttc ccctccgtgt ctcagcagca gctgtgagaa atgctttgca tctgtgacct 360

ttatgaaggg gaacttccat gctgaatgag ggtaggatta catgctcctg tttcccgggg 420

gtcaagaaag cctcagactc cagcatgata agcagggtga g 461

48

571

Homo sapien

48

ataggggctt taaggaggga attcaggttc aatgaggtcg taaggccagg gctcttatcc 60

agtaagactg gggtccttag atgagaaaga gacacccgag gtccttctct ctgccgtgtg 120

aggatgcatc aagaaggcgg ccgtctgcaa gcgaaggaga ggccgcacca gaaaccgaca 180

ccttcatctt ggacttgcag cctctagaac tgagaaaata actgtctgtt ggttaagcca 240

cccagtttgt agtattctct tatggcttcc taagcagact aacaaacaaa cacccaaaat 300

taactgatgg cttcgctgtc ttctgtaaaa attgctatga gagaactttt cactcactgt 360

tttgcagttt ctccctcagt ccctggttct ttcttctcac ataatcccaa tttcaattta 420

tagttcatgg cccaggcaga gtcattcatc acggcatctc ctgagctaaa ccagcacctg 480

ctctgctcac ttcttgactg gctgctcatc atcagccctc ttgcagagat ttcatttcct 540

cccgtgccag gtacttcacg caccaagctc a 571

49

511

Homo sapien

49

ggataatgaa gttgttttat ttagcttgga caaaaaggca tattcctcta ttttcttata 60

caacaaatat ccccaaaata aagcaagcat atatatcttg aatgtgtaat aatccagtga 120

taaacaagag cagtacttta aaagaaaaaa aaatatgtat ttctgtcagg ttaaaatgag 180

aatcaaaacc atttactctg ctaactcatt attttttgct ttctttttgg ttaagagagg 240

caatgcaata cactgaaaaa ggtttttatc ttatctggca ttggaattag acatattcaa 300

accccagccc ccatttccaa actttaagac cacaaacaag taatttactt ttctgaacat 360

tggttttttc tggaaaatgg gaattataaa atagactttg cagactctta tgagattaaa 420

taagataatg tatgaaattc tttcttcttt tttacttctt tttccttttt gagatggagt 480

ctcaccccgt cacccaggct ggagtacagt g 511

50

561

Homo sapien

50

ccactgcact ccagcctggg tgacggagtg agactctgtc tcaaaaaaac aaacaaacaa 60

acaaacaaaa aactgaaaag gaaatagagt tcctctttcc tcatatatga atatattatt 120

tcaacagatt gttgatcacc taccatatgc ttggtattgt tctaattgct ggggatacag 180

caagaggttc tgcagaactt catggagcat gaaagtaaat aaacaaagtt aatttcaagg 240

ccaggcatgg ttgctcacac ctttagtccc agcactttgg gaggctgagg caggtggatc 300

acttgggccc aggagttcaa ggctgcagtg agccaagatt gtgccactac tctccaggct 360

gggcaacaga gcaagaccct gtctcagggg gaacaaaaag ttaatttcag attttgttaa 420

gtgctgtaaa ggaagtaaat aggttgatat tcaagagagc acctgaaggc caggcgtggt 480

ggctcacgcc tgtggtctaa cgctttggga agcccgagcg ggcggatcac aaggtcagga 540

gaattttggc caggcatggt g 561

51

451

Homo sapien

51

agaatccatt tattgggttt taaactagtt acacaactga aatcagtttg gcactacttt 60

atacagggat tacgcctgtg tatgccgaca cttaaatact gtaccaggac cactgctgtg 120

cttaggtctg tattcagtca ttcagcatgt agatactaaa aatatactgt agtgttcctt 180

taaggaagac tgtacagggt gtgttgcaag atgacattca ccaatttgtg aattatttca 240

acccagaaga tacctttcac tctataaact tgtcataggc aaacatgtgg tgttagcatt 300

gagagatgca cacaaaaatg ttacataaaa gttcagacat tctaatgata agtgaactga 360

aaaaaaaaaa aaccccacat ctcaattttt gtaacaagat aaagaaaata atttaaaaac 420

acaaaaaatg gcattcagtg ggtacaaagc c 451

52

682

Homo sapien

52

caaatattta atataaatct ttgaaacaag ttcagakgaa ataaaaatca aagtttgcaa 60

aaacgtgaag attaacttaa ttgtcaaata ttcctcattg ccccaaatca gtattttttt 120

tatttctatg caaaagtatg ccttcaaact gcttaaatga tatatgatat gatacacaaa 180

ccagttttca aatagtaaag ccagtcatct tgcaattgta agaaataggt aaaagattat 240

aagacacctt acacacacac acacacacac acacacacgt gtgcaccgcc aatgacaaaa 300

aacaatttgg cctctcctaa aataagaaca tgaagaccct taattgctgc caggagggaa 360

cactgtgtca cccctcccta caatccaggt agtttccttt aatccaatag caaatctggg 420

catatttgag aggagtgatt ctgacagcca csgttgaaat cctgtgggga accattcatg 480

tccacccact ggtgccctga aaaaatgcca ataatttttc gctcccactt ctgctgctgt 540

ctcttccaca tcctcacata gaccccagac ccgctggccc ctggctgggc atcgcattgc 600

tggtagagca agtcataggt ctcgtctttg acgtcacaga agcgatacac caaattgcct 660

ggtcggtcat tgtcataacc ag 682

53

tttgacttta gtaggggtct gaactattta ttttactttg ccmgtaatat ttaraccyta 60

tatatctttc attatgccat cttatcttct aatgbcaagg gaacagwtgc taamctggct 120

tctgcattwa tcacattaaa aatggctttc ttggaaaatc ttcttgatat gaataaagga 180

tcttttavag ccatcattta aagcmggntt ctctccaaca cgagtctgct sasggggggk 240

gagctgtgaa ctctggctga aggctttccc atacacactg caatgacmtg gtttctgacc 300

agbgtgagtt a 311

54

561

Homo sapien

54

agagaagccc cataaatgca atcagtgtgg gaaggccttc agtcagagct caagcctttt 60

cctccatcat cgggttcata ctggagagaa accctatgta tgtaatgaat gcggcagagc 120

ctttggtttt aactctcatc ttactgaaca cgtaaggatt cacacaggag aaaaacccta 180

tgtttgtaat gagtgcggca aagcctttcg tcggagttcc actcttgttc agcatcgaag 240

agttcacact ggggagaagc cctaccagtg cgttgaatgt gggaaagctt tcagccagag 300

ctcccagctc accctacatc agccgagttc acactggaga gaagccctat gactgtggtg 360

actgtgggaa ggccttcagc cggaggtcaa ccctcattca gcatcagaaa gttcacagcg 420

gagagactcg taagtgcaga aaacatggtc cagcctttgt tcatggctcc agcctcacag 480

cagatggaca gattcccact ggagagaagc acggcagaac ctttaaccat ggtgcaaatc 540

tcattctgcg ctggacagtt c 561

55

811

Homo sapien

55

gagacagggt ctcactttgt cacccaggct ggaatgcagt ggtgcgatct tacgtagctc 60

actgcagccc tgacctcctg gactcaaaca attctcctgc ctcagccctg caagtagctg 120

ggactgtggg tgcatgccac catgcctggc taacttttgt agtttttgta aagatggggt 180

tttgccatgt tgcacatgct ggtcttgaac tcctgagctc aaacgatctg cccacctcgg 240

cctcccagaa tgttgggatt acaggggtaa accaccacgc ctggccccat tagggtattc 300

ttagcatcca cttgctcact gagattaatc ataagagatg ataagcactg gaagaaaaaa 360

atttttacta ggctttggat atttttttcc tttttcagct ttatacagag gattggatct 420

ttagttttcc tttaactgat aataaaacat tgaaaggaaa taagtttacc tgagattcac 480

agagataacc ggcatcactc ccttgctcaa ttccagtctt taccacatca attattttca 540

gaggtgcagg ataaaggcct ttagtctgct ttcgcacttt ttcttccact tttttgtaaa 600

cctgttgcct gacaaatgga attgacagcg tatgccatga ctattccatt tgtcaggcat 660

acgctgtcaa tttttccacc aatcccttgt ctctctttgg agagatcttc ttatcagcta 720

gtcctttggc aaaagtaatt gcaacttctt ctaggtattc tattgtccgt tccactggtg 780

gaacccctgg gaccaggact aaaacctcca g 811

56

atctcatata tatatttctt cctgacttta tttgcttgct tctgncacgc atttaaaata 60

tcacagagac caaaatagag cggctttctg gtggaacgca tggcagtcac aggacaaaat 120

acaaaactag ggggctctgt cttctcatac atcatacaat tttcaagtat tttttttatg 180

tacaaagagc tactctatct gaaaaaaaat taaaaaataa atgagacaag atagtttatg 240

catcctagga agaaagaatg ggaagaaaga acggggcagt tgggtacaga ttcctgtccc 300

ctgttcccag ggaccactac cttcctgcca ctgagttccc ccacagcctc acccatcatg 360

tcacagggca agtgccaggg taggtgggga ccagtggaga caggaaccag caacatactt 420

tggcctggaa gataaggaga aagtctcaga aacacactgg tgggaagcaa tcccacnggc 480

cgtgccccan gagcttccca cctgctgctg gctccctggg tggctttggg aacagcttgg 540

gcaggccctt ttgggtgggg nccaactggg cctttgggcc cgtgtggaaa g 591

57

481

Homo sapien

57

aaacattgag atggaatgat agggtttccc agaatcaggt ccatatttta actaaatgaa 60

aattatgatt tatagccttc tcaaatacct gccatacttg atatctcaac cagagctaat 120

tttacctctt tacaaattaa ataagcaagt aactggatcc acaatttata atacctgtca 180

attttttctg tattaaacct ctatcatagt ttaagcctat tagggtactt aatccttaca 240

aataaacagg tttaaaatca cctcaatagg caactgccct tctggttttc ttctttgact 300

aaacaatctg aatgcttaag attttccact ttgggtgcta gcagtacaca gtgttacact 360

ctgtattcca gacttcttaa attatagaaa aaggaatgta cactttttgt attctttctg 420

agcagggccg ggaggcaaca tcatctacca tggtagggac ttgtatgcat ggactacttt 480

a 481

58

141

Homo sapien

58

actctgtcgc ccaggctgga gcccabtggm gcgatctcga ctccctgcaa gctmcgcctc 60

acaggwtcat gccattctcc tgcctcagca tctggagtag ctgggactac aggcgccagc 120

caccatgccc agctaatttt t 141

59

191

Homo sapien

59

accttaaaga cataggagaa tttatactgg gagagaaagc ttacaaatgt aaggtttctg 60

acaagacttg ggagtgattc acacctggaa caacatactg gacttcacac tggabagaaa 120

ccttacaagt gtaatgagtg tggcaaagcc tttggcaagc agtcaacact tattcaccat 180

caggcaattc a 191

60

480

Homo sapien

60

agtcaggatc atgatggctc agtttcccac agcgatgaat ggagggccaa atatgtgggc 60

tattacatct gaagaacgta ctaagcatga taaacagttt gataacctca aaccttcagg 120

aggttacata acaggtgatc aagcccgtac ttttttccta cagtcaggtc tgccggcccc 180

ggttttagct gaaatatggg ccttatcaga tctgaacaag gatgggaaga tggaccagca 240

agagttctct atagctatga aactcatcaa gttaaagttg cagggccaac agctgcctgt 300

agtcctccct cctatcatga aacaaccccc tatgttctct ccactaatct ctgctcgttt 360

tgggatggga agcatgccca atctgtccat tcatcagcca ttgcctccag ttgcacctat 420

agcaacaccc ttgtcttctg ctacttcagg gaccagtatt cctccctaat gatgcctgct 480

61

381

Homo sapien

61

ctttcgattt ccttcaattt gtcacgtttg attttatgaa gttgttcaag ggctaactgc 60

tgtgtattat agctttctct gagttccttc agctgattgt taaatgaatc catttctgag 120

agcttagatg cagtttcttt ttcaagagca tctaattgtt ctttaagtct ttggcataat 180

tcttcctttt ctgatgactt tctatgaagt aaactgatcc ctgaatcagg tgtgttactg 240

agctgcatgt ttttaattct ttcgtttaat agctgcttct cagggaccag atagataagc 300

ttattttgat attccttaag ctcttggtga agttgttcga tttccataat ttccaggtca 360

cactggttat cccaaacttc t 381

62

906

Homo sapien

62

gtggaggtga aacggaggca agaaaggggg ctacctcagg agcgagggac aaagggggcg 60

tgaggcacct aggccgcggc accccggcga caggaagccg tcctgaaccg ggctaccggg 120

taggggaagg gcccgcgtag tcctcgcagg gccccagagc tggagtcggc tccacagccc 180

cgggccgtcg gcttctcact tcctggacct ccccggcgcc cgggcctgag gactggctcg 240

gcggagggag aagaggaaac agacttgagc agctccccgt tgtctcgcaa ctccactgcc 300

gaggaactct catttcttcc ctcgctcctt caccccccac ctcatgtaga aaggtgctga 360

agcgtccgga gggaagaaga acctgggcta ccgtcctggc cttcccmccc ccttcccggg 420

gcgctttggt gggcgtggag ttggggttgg gggggtgggt gggggttctt ttttggagtg 480

ctggggaact tttttccctt cttcaggtca ggggaaaggg aatgcccaat tcagagagac 540

atgggggcaa gaaggacggg agtggaggag cttctggaac tttgcagccg tcatcgggag 600

gcggcagctc taacagcaga gagcgtcacc gcttggtatc gaagcacaag cggcataagt 660

ccaaacactc caaagacatg gggttggtga cccccgaagc agcatccctg ggcacagtta 720

tcaaaccttt ggtggagtat gatgatatca gctctgattc cgacaccttc tccgatgaca 780

tggccttcaa actagaccga agggagaacg acgaacgtcg tggatcagat cggagcgacc 840

gcctgcacaa acatcgtcac caccagcaca ggcgttcccg ggacttacta aaagctaaac 900

agaccg 906

63

491

Homo sapien

63

gacatgtttg cctgcagggg accagagaca atgggattag ccagtgctca ctgttcttta 60

tgcttccaga gaggatgggg acagctctca ggtcagaatc caggctgaga aggccatgct 120

ggttgggggc ccccggaagc acggtccgga tcctccctgg catcagcgta gacccgctgc 180

tcaggcttgg ggtaccaaac tcatgctctg tactgttttg gccccatgcg gtgagaggaa 240

aacctagaaa aagattggtc gtgctaagga atcagctgcc ccctcatcct ccgcatccaa 300

tgctggtgac aacatattcc ctctcccagg acacagactc ggtgactcca cactgggctg 360

agtggcctct ggaggctcgt ggcctaaggc agggctccgt aaggctgatc ggctgaactg 420

ggtggggtga gggtttctga cccttcgctt cccatcccat aaccgctgtc aatgagctca 480

cactgtggtc a 491

64

511

Homo sapien

64

gatggcatgg tcgttgctaa tgtgcctgct gggatggagc acttcctcct gtgagcccag 60

gggacccgcc tgtccctgga gcttggggca aggagggaag agtgatacca ggaaggtggg 120

gctgcagcca ggggccagag tcagttcagg gagtggtcct cggccctcaa agctcctccg 180

gggactgctc aggagtgatg gtgccctgga gtttgcccca acttccctgg ccaccctgga 240

aggtgcctgg ctgctccagg cctctaggct gggctgatgg gtttctccag gacacaagta 300

tcattaaagc caccctctcc tcagcttgtc aggccgcaca tgtgggacag gctgtgctca 360

caaccccctc gcctgccctg ccctccatca ggaggagcca gtggaacctt cggaaagctc 420

ccagcatctc agcagccctc aaaagtcgtc ctggggcaag ctctggttct cctgactgga 480

ggtcatctgg gcttggcctg ctctctctcg c 511

65

394

Homo sapien

65

taaaaaagtg taacaaaggt ttatttagac tttcttcatg cccccagatc caggatgtct 60

atgtaaaccg ttatcttaca aagaaagcac aatatttggt ataaactaag tcagtgactt 120

gcttaactga aatagcgtcc atccaaaagt gggtttaagg taaaactacc tgacgatatt 180

ggcggggatc ctgcagtttg gactgcttgc cgggtttgtc cagggttccg ggtctgttct 240

tggcactcat ggggacaggc atcctgctcg tctgtggggc cccgctggag cccttacgtg 300

aagctgaagg tatcgaccst agggggctct agggcagtgg gaccttcatc cggaactaac 360

aagggtcggg gagaggcctc ttgggctatg tggg 394

66

359

Homo sapien

66

caagcgttcc tttatggatg taaattcaaa cagtcatgct gagccatccc gggctgacag 60

tcacgttwaa gacactaggt cgggcgccac agtgccaccc aaggagaaga agaatttgga 120

atttttccat gaagatgtac ggaaatctga tgttgaatat gaaaatggcc cccaaatgga 180

attccaaaag gttaccacag gggctgtaag acctagtgac cctcctaagt gggaaagagg 240

aatggagaat agtatttctg atgcatcaag aacatcagaa tataaaactg agatcataat 300

gaaggaaaat tccatatcca atatgagttt actcagagac agtagaaact attcccagg 359

67

taggaataac aaatgtttat tcagaaatgg ataagtaata cataatcacc cttcatctct 60

taatgcccct tcctctcctt ctgcacagga gacacagatg ggtaacatag aggcatggga 120

agtggaggag gacacaggac tagcccacca ccttctcttc ccggtctccc aagatgactg 180

cttatagagt ggaggaggca aacaggtccc ctcaatgtac cagatggtca cctatagcac 240

cagctccaga tggccacgtg gttgcagctg gactcaatga aactctgtga caaccagaag 300

atacctgctt tgggatgaga gggaggataa agccatgcag ggaggatatt taccatccct 360

accctaagca cagtgcaagc agtgagcccc cggctcccag tacctgaaaa accaaggcct 420

actgnctttt ggatgctctc ttgggccacg 450

68

511

Homo sapien

68

aagcctcctg ccctggaaat ctggagcccc ttggagctga gctggacggg gcagggaggg 60

gctgagaggc aagaccgtct ccctcctgct gcagctgctt ccccagcagc cactgctggg 120

cacagcagaa acgccagcag agaaaatggg agccgagagt ccttagccct ggagctgagg 180

ctgcctctgg gctgacccgc tggctgtacg tggccagaac tggggttggc atctggcatc 240

catttgaggc cagggtggag gaaagggagg ccaacagagg aaaacctatt cctgctgtga 300

caacacagcc cttgtcccac gcagcctaag tgcagggagc gtgatgaagt caggcagcca 360

gtcggggagg acgaggtaac tcagcagcaa tgtcaccttg tagcctatgc gctcaatggc 420

ccggaggggc agcaaccccc cgcacacgtc agccaacagc agtgcctctg caggcaccaa 480

gagagcgatg atggacttga gcgccgtgtt c 511

69

511

Homo sapien

69

gtttggcaga agacatgttt aataacattt tcatatttaa aaaatacagc aacaattctc 60

tatctgtcca ccatcttgcc ttgcccttcc tggggctgag gcagacaaag gaaaggtaat 120

gaggttaggg cccccaggcg ggctaagtgc tattggcctg ctcctgctca aagagagcca 180

tagccagctg ggcacggccc cctagcccct ccaggttgct gaggcggcag cggtggtaga 240

gttcttcact gagccgtggg ctgcagtctc gcagggagaa cttctgcacc agccctggct 300

ctacggcccg aaagaggtgg agccctgaga accggaggaa aacatccatc acctccagcc 360

cctccagggc ttcctcctct tcctggcctg ccagttcacc tgccagccgg gctcgggccg 420

ccaggtagtc agcgttgtag aagcagccct ccgcagaagc ctgccggtca aatctccccg 480

ctataggagc cccccgggag gggtcagcac c 511

70

511

Homo sapien

70

caagttgaac gtcaggcttg gcagaggtgg agtgtagatg aaaacaaagg tgtgattatg 60

aagaggatgt gagtcctttg ggtgtaggag agaaaggctg ttgagcttct atttcaagat 120

acttttacct gtgcaaaaag cacattttcc acctccttct catggcattt gtgtaaggtg 180

agtatgattc ctattccatc tgcattttag aggtgaagaa taacgtacaa gggattcagt 240

gattagcaag ggacccctca ctaagtgttg atggagttag gacagagctc agctgtttga 300

atctcagagc ccaggcagct ggagctgggt aggatcctgg agctggcact aatgtgaggt 360

gcattccctc caacccaggc tcagatccgg aacctgaccg tgctgacccc cgaaggggag 420

gcagggctga gctggcccgt tgggctccct gctcctttca caccacactc tcgctttgag 480

gtgctgggct gggactactt cacagagcag c 511

71

511

Homo sapien

71

tggcctgggc aggattggga gagaggtagc tacccggatg cagtcctttg ggatgaagac 60

tatagggtat gaccccatca tttccccaga ggtctcggcc tcctttggtg ttcagcagct 120

gcccctggag gagatctggc ctctctgtga tttcatcact gtgcacactc ctctcctgcc 180

ctccacgaca ggcttgctga atgacaacac ctttgcccag tgcaagaagg gggtgcgtgt 240

ggtgaactgt gcccgtggag ggatcgtgga cgaaggcgcc ctgctccggg ccctgcagtc 300

tggccagtgt gccggggctg cactggacgt gtttacggaa gagccgccac gggaccgggc 360

cttggtggac catgagaatg tcatcagctg tccccacctg ggtgccagca ccaaggaggc 420

tcagagccgc tgtggggagg aaattgctgt tcagttcgtg gacatggtga aggggaaatc 480

tctcacgggg gttgtgaatg cccaggccct t 511

72

2017

Homo sapien

72

agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag 60

cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata 120

aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt 180

ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc 240

tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt 300

taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta 360

tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc 420

atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga 480

ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt acatcctcat 540

taccaaatgg aactgccagt ctcattcagc ctttatccat tccttattct tcttcaacat 600

tgcctcatgc atcatcttac agcctgatga tgggaggatt tggtggtgct agtatccaga 660

aggcccagtc tctgattgat ttaggatcta gtagctcaac ttcctcaact gcttccctct 720

cagggaactc acctaagaca gggacctcag agtgggcagt tcctcagcct tcaagattaa 780

agtatcggca aaaatttaat agtctagaca aaggcatgag cggatacctc tcaggttttc 840

aagctagaaa tgcccttctt cagtcaaatc tctctcaaac tcagctagct actatttgga 900

ctctggctga catcgatggt gacggacagt tgaaagctga agaatttatt ctggcgatgc 960

acctcactga catggccaaa gctggacagc cactaccact gacgttgcct cccgagcttg 1020

tccctccatc tttcagaggg ggaaagcaag ttgattctgt taatggaact ctgccttcat 1080

atcagaaaac acaagaagaa gagcctcaga agaaactgcc agttactttt gaggacaaac 1140

ggaaagccaa ctatgaacga ggaaacatgg agctggagaa gcgacgccaa gtgttgatgg 1200

agcagcagca gagggaggct gaacgcaaag cccagaaaga gaaggaagag tgggagcgga 1260

aacagagaga actgcaagag caagaatgga agaagcagct ggagttggag aaacgcttgg 1320

agaaacagag agagctggag agacagcggg aggaagagag gagaaaggag atagaaagac 1380

gagaggcagc aaaacaggag cttgagagac aacgccgttt agaatgggaa agactccgtc 1440

ggcaggagct gctcagtcag aagaccaggg aacaagaaga cattgtcagg ctgagctcca 1500

gaaagaaaag tctccacctg gaactggaag cagtgaatgg aaaacatcag cagatctcag 1560

gcagactaca agatgtccaa atcagaaagc aaacacaaaa gactgagcta gaagttttgg 1620

ataaacagtg tgacctggaa attatggaaa tcaaacaact tcaacaagag cttaaggaat 1680

atcaaaataa gcttatctat ctggtccctg agaagcagct attaaacgaa agaattaaaa 1740

acatgcagct cagtaacaca cctgattcag ggatcagttt acttcataaa aagtcatcag 1800

aaaaggaaga attatgccaa agacttaaag aacaattaga tgctcttgaa aaagaaactg 1860

catctaagct ctcagaaatg gattcattta acaatcagct gaaggaactc agagaaagct 1920

ataatacaca gcagttagcc cttgaacaac ttcataaaat caaacgtgac aaattgaagg 1980

aaatcgaaag aaaaagatta gagcaaaaaa aaaaaaa 2017

73

414

Homo sapien

73

atggcagtga cattcaccat catgggaacc accttccctt ttcttcagga ttctctgtag 60

tggaagagag cacccagtgt tgggctgaaa acatctgaaa gtagggagaa gaacctaaaa 120

taatcagtat ctcagagggc tctaaggtgc caagaagtct cactggacat ttaagtgcca 180

acaaaggcat actttcggaa tcgccaagtc aaaactttct aacttctgtc tctctcagag 240

acaagtgaga ctcaagagtc tactgcttta gtggcaacta cagaaaactg gtgttaccca 300

gaaaaacagg agcaattaga aatggttcca atatttcaaa gctccgcaaa caggatgtgc 360

tttcctttgc ccatttaggg tttcttctct ttcctttctc tttattaacc acta 414

74

1567

Homo sapien

74

atatctagaa gtctggagtg agcaaacaag agcaagaaac aaaaagaagc caaaagcaga 60

aggctccaat atgaacaaga taaatctatc ttcaaagaca tattagaagt tgggaaaata 120

attcatgtga actagacaag tgtgttaaga gtgataagta aaatgcacgt ggagacaagt 180

gcatccccag atctcaggga cctccccctg cctgtcacct ggggagtgag aggacaggat 240

agtgcatgtt ctttgtctct gaatttttag ttatatgtgc tgtaatgttg ctctgaggaa 300

gcccctggaa agtctatccc aacatatcca catcttatat tccacaaatt aagctgtagt 360

atgtacccta agacgctgct aattgactgc cacttcgcaa ctcaggggcg gctgcatttt 420

agtaatgggt caaatgattc actttttatg atgcttccaa aggtgccttg gcttctcttc 480

ccaactgaca aatgccaaag ttgagaaaaa tgatcataat tttagcataa acagagcagt 540

cggcgacacc gattttataa ataaactgag caccttcttt ttaaacaaac aaatgcgggt 600

ttatttctca gatgatgttc atccgtgaat ggtccaggga aggacctttc accttgacta 660

tatggcatta tgtcatcaca agctctgagg cttctccttt ccatcctgcg tggacagcta 720

agacctcagt tttcaatagc atctagagca gtgggactca gctggggtga tttcgccccc 780

catctccggg ggaatgtctg aagacaattt tgttacctca atgagggagt ggaggaggat 840

acagtgctac taccaactag tggataaagg ccagggatgc tgctcaacct cctaccatgt 900

acaggacgtc tccccattac aactacccaa tccgaagtgt caactgtgtc aggactaaga 960

aaccctggtt ttgagtagaa aagggcctgg aaagagggga gccaacaaat ctgtctgctt 1020

cctcacatta gtcattggca aataagcatt ctgtctcttt ggctgctgcc tcagcacaga 1080

gagccagaac tctatcgggc accaggataa catctctcag tgaacagagt tgacaaggcc 1140

tatgggaaat gcctgatggg attatcttca gcttgttgag cttctaagtt tctttccctt 1200

cattctaccc tgcaagccaa gttctgtaag agaaatgcct gagttctagc tcaggttttc 1260

ttactctgaa tttagatctc cagacccttc ctggccacaa ttcaaattaa ggcaacaaac 1320

atataccttc catgaagcac acacagactt ttgaaagcaa ggacaatgac tgcttgaatt 1380

gaggccttga ggaatgaagc tttgaaggaa aagaatactt tgtttccagc ccccttccca 1440

cactcttcat gtgttaacca ctgccttcct ggaccttgga gccacggtga ctgtattaca 1500

tgttgttata gaaaactgat tttagagttc tgatcgttca agagaatgat taaatataca 1560

tttccta 1567

75

240

Homo sapien

75

tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca 60

gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat 120

ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat 180

ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct 240

76

tagcgyggtc gcggccgagg yctgcttytc tgtccagccc agggcctgtg gggtcagggc 60

ggtgggtgca gatggcatcc actccggtgg cttccccatc tttctctggc ctgagcaagg 120

tcagcctgca gccagagtac agagggccaa cactggtgtt cttgaacaag ggccttagca 180

ggccctgaag grccctctct gtagtgttga acttcctgga gccaggccac atgttctcct 240

cataccgcag gytagygatg gtgaagttga gggtgaaata gtattmangr agatggctgg 300

caracctgcc cgggcggccg ctcsaaatcc 330

77

361

Homo sapien

77

agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca 60

gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg 120

cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg 180

acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc 240

cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac 300

ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg 360

a 361

78

ttggggnttt mgagcggccg cccgggcagg taccggggtg gtcagcgagg agccattcac 60

actgaacttc accatcaaca acctgcggta tgaggagaac atgcagcacc ctggctccag 120

gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt tcaagagcac 180

cagtgttggc cctctgtact ctggctgcag actgactttg ctcagacttg agaaacatgg 240

ggcagccact ggagtggacg ccatctgcac cctccgcctt gatcccactg gtcctggact 300

ggacagagag cggctatact gggagctgag ccagtcctct ggcggngacn ccnctt 356

79

226

Homo sapien

79

agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt 60

gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg 120

catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct 180

cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga 226

80

tgtggtgttg aacttcctgg agncagggtg acccatgtcc tccccatact gcaggttggt 60

gatggtgaag ttgagggtga atggtaccag gagagggcca gcagccataa ttgtsgrgck 120

gsmgmssgag gmwggwgtyy cwgaggttcy rarrtccact gtggaggtcc caggagtgct 180

ggtggtgggc acagagstcy gatgggtgaa accattgaca tagagactgt tcctgtccag 240

ggtgtagggg cccagctctt yratgycatt ggycagttkg ctyagctccc agtacagccr 300

ctctckgyyg mgwccagsgc ttttggggtc aagatgatgg atgcagatgg catccactcc 360

agtggctgct ccatccttct cggacctgag agaggtcagt ctgcagccag agtacagagg 420

gccaacactg gtgttctttg aata 444

81

310

Homo sapien

81

tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga 60

ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca 120

gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt 180

acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctct 240

tccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg 300

ttggtgatgg 310

82

acggtttcaa tggacacttt tattgtttac ttaatggatc atcaattttg tctcactacc 60

tacaaatgga atttcatctt gtttccatgc tgagtagtga aacagtgaca aagctaatca 120

taataaccta catcaaaaga gaactaagct aacactgctc actttctttt taacaggcaa 180

aatataaata tatgcactct anaatgcaca atggtttagt cactaaaaaa ttcaaatggg 240

atcttgaaga atgtatgcaa atccagggtg cagtgaagat gagctgagat gctgtgcaac 300

tgtttaaggg ttcctggcac tgcatctctt ggccactagc tgaatcttga catggaaggt 360

tttagctaat gccaagtgga gatgcagaaa atgctaagtt gacttagggg ctgtgcacag 420

gaactaaaag gcaggaaagt actaaatatt gctgagagca tccaccccag gaaggacttt 480

accttccagg agctccaaac tggcaccacc cccagtgctc acatggctga ctttatcctc 540

cgtgttccat ttggcacagc aagtggcagt g 571

83

551

Homo sapien

83

aaggctggtg ggtttttgat cctgctggag aacctccgct ttcatgtgga ggaagaaggg 60

aagggaaaag atgcttctgg gaacaaggtt aaagccgagc cagccaaaat agaagctttc 120

cgagcttcac tttccaagct aggggatgtc tatgtcaatg atgcttttgg cactgctcac 180

agagcccaca gctccatggt aggagtcaat ctgccacaga aggctggtgg gtttttgatg 240

aagaaggagc tgaactactt tgcaaaggcc ttggagagcc cagagcgacc cttcctggcc 300

atcctgggcg gagctaaagt tgcagacaag atccagctca tcaataatat gctggacaaa 360

gtcaatgaga tgattattgg tggtggaatg gcttttacct tccttaaggt gctcaacaac 420

atggagattg gcacttctct gtttgatgaa gagggagcca agattgtcaa agacctaatg 480

tccaaagctg agaagaatgg tgtgaagatt accttgcctg ttgactttgt cactgctgac 540

aagtttgatg a 551

84

571

Homo sapien

84

tttgttcctt acatttttct aaagagttac ttaaatcagt caactggtct ttgagactct 60

taagttctga ttccaactta gctaattcat tctgagaact gtggtatagg tggcgtgtct 120

cttctagctg ggacaaaagt tctttgtttt ccccctgtag agtatcacag accttctgct 180

gaagctggac ctctgtctgg gccttggact cccaaatctg cttgtcatgt tcaagcctgg 240

aaatgttaat ctttaattct tccatatgga tggacatctg tctaagttga tcctttagaa 300

cactgcaatt atcttctttg agtctaattt cttcttcttt gctttgaatc gcatcactaa 360

acttcctctc ccatttctta gcttcatcta tcaccctgtc acgatcatcc tggagggaag 420

acatgctctt agtaaaggct gcaagctggg tcacagtact gtccaagttt tcctgaagtt 480

gctgaacttc cttgtctttc ttgttcaaag taacctgaat ctctccaatt gtctcttcca 540

agtggacttt ttctctgcgc aaagcatcca g 571

85

561

Homo sapien

85

tcattgcctg tgatggcatc tggaatgtga tgagcagcca ggaagttgta gatttcattc 60

aatcaaagga ttcagcatgt ggtggaagct gtgaggcaag agaaacaaga actgtatggc 120

aagttaagaa gcacagaggc aaacaagaag gagacagaaa agcagttgca ggaagctgag 180

caagaaatgg aggaaatgaa agaaaagatg agaaagtttg ctaaatctaa acagcagaaa 240

atcctagagc tggaagaaga gaatgaccgg cttagggcag aggtgcaccc tgcaggagat 300

acagctaaag agtgtatgga aacacttctt tcttccaatg ccagcatgaa ggaagaactt 360

gaaagggtca aaatggagta tgaaaccctt tctaagaagt ttcagtcttt aatgtctgag 420

aaagactctc taagtgaaga ggttcaagat ttaaagcatc agatagaagg taatgtatct 480

aaacaagcta acctagaggc caccgagaaa catgataacc aaacgaatgt cactgaagag 540

ggaacacagt ctataccagg t 561

86

795

Homo sapien

86

aagccaataa tcaccattta ttacttaata tatgccaacc actgtacttg gcagttcaca 60

aattctcacc gttacaacaa ccccatgagg tatttattcc cattctatag atagggaaac 120

cacagctcaa gtaagttagg aaactgagcc aagtatacac agaatacgaa gtggcaaaac 180

tagaaggaaa gactgacact gctatctgct ggcctccagt gtcctggctc ttttcacacg 240

ggttcaatgt ctccagcgct gctgctgctg ctgcattacc atgccctcat tgtttttctt 300

cctctggtgt tcaactgcat ccttcaaaga atctaactca ttccagagac cacttatttc 360

tttctctctt tctgaaatta cttttaataa ttcttcatga gggggaaaag aagatgcctg 420

ttggtagttt tgttgtttaa gctgctcaat ttgggactta aacaatttgt tttcatcttg 480

tacatcctgt aacagctgtg ttttgctaga aagatcactc tccctctctt ttagcatggc 540

ttctaacctc ttcaattcat tttccttttc tttcaacaca atctcaagtt cttcaaactg 600

tgatgcagaa gaggcctctt tcaagttatg ttgtgctact tcctgaacat gtgcttttaa 660

agattcattt tcttcttgaa gatcctgtaa ccacttccct gtattggcta ggtctttctc 720

tttctcttcc aaaacagcct tcatggtatt catctgttcc tcttttcctt ttaataagtt 780

caggagcttc agaac 795

87

594

Homo sapien

87

caagcttttt tttttttttt aaaaagtgtt agcattaatg ttttattgtc acgcagatgg 60

caactgggtt tatgtcttca tattttatat ttttgtaaat taaaaaaatt acaagtttta 120

aatagccaat ggctggttat attttcagaa aacatgatta gactaattca ttaatggtgg 180

cttcaagctt ttccttattg gctccagaaa attcacccac cttttgtccc ttcttaaaaa 240

actggaatgt tggcatgcat ttgacttcac actctgaagc aacatcctga cagtcatcca 300

catctacttc aaggaatatc acgttggaat acttttcaga gagggaatga aagaaaggct 360

tgatcatttt gcaaggccca caccacgtgg ctgagaagtc aactactaca agtttatcac 420

ctgcagcgtc caaggcttcc tgaaaagcag tcttgctctc gatctgcttc accatcttgg 480

ctgctggagt ctgacgagcg gctgtaagga ccgatggaaa tggatccaaa gcaccaaaca 540

gagcttcaag actcgctgct tggcttgaat tcggatccga tatcgccatg gcct 594

88

557

Homo sapien

88

aagtgttagc attaatgttt tattgtcacg cagatggcaa ctgggtttat gtcttcatat 60

tttatatttt tgtaaattaa aaaaattmca agttttaaat agccaatggc tggttatatt 120

ttcagaaaac atgattagac taattcatta atggtggctt caagcttttc cttattggct 180

ccagaaaatt cacccacctt ttgtcccttc ttaaaaaact ggaatgttgg catgcatttg 240

acttcacact ctgaagcaac atcctgacag tcatccacat ctacttcaag gaatatcacg 300

ttggaatact tttcagagag ggaatgaaag aaaggcttga tcattttgca aggcccacac 360

cacgtggctg agaagtcaac tactacaagt ttatcacctg cagcgtccaa ggcttcctga 420

aaagcagtct tgctctcgat ctgcttcacc atcttggctg ctggagtctg acgagcggct 480

gtaaggaccg atggaaatgg atccaaagca ccaaacagag cttcaagact cgctgcttgg 540

catgaattcg gatccga 557

89

tacaaacttt attgaaacgc acacgcgcac acacacaaac acccctgtgg atagggaaaa 60

gcacctggcc acagggtcca ctgaaacggg gaggggatgg cagcttgtaa tgtggctttt 120

gccacaaccc ccttctgaca gggaaggcct tagattgagg ccccacctcc catggtgatg 180

gggagctcag aatggggtcc agggagaatt tggttagggg gaggtgctag ggaggcatga 240

gcagagggca ccctccgagt ggggtcccga gggctgcaga gtcttcagta ctgtccctca 300

cagcagctgt ctcaaggctg ggtccctcaa aggggcgtcc cagcgcgggg cctccctgcg 360

caaacacttg gtacccctgg ctgcgcagcg gaagccagca ggacagcagt ggcgccgatc 420

agcacaacag acgccctggc ggtagggaca gcaggcccag ccctgtcggt tgtctcggca 480

gcaggtctgg ttatcatggc agaagtgtcc ttcccacact tcacgtcctt cacacccacg 540

tganggctac nggccaggaa g 561

90

561

Homo sapien

90

cccgtgggtg ccatccacgg agttgttacc tgatctttgg aagcaggatc gcccgtctgc 60

actgcagtgg aagccccgtg ggcagcagtg atggccatcc ccgcatgcca cggcctctgg 120

gaaggggcag caactggaag tccctgagac ggtaaagatg caggagtggc cggcagagca 180

gtgggcatca acctggcagg ggccacccag atgcctgctc agtgttgtgg gccatttgtc 240

cagaagggga cggcagcagc tgtagctggc tcctccgggg tccaggcagc aggccacagg 300

gcagaactga ccatctgggc accgcgttcc agccaccagc cctgctgtta aggccaccca 360

gctcaccagg gtccacatgg tctgcctgcg tccgactccg cggtccttgg gccctgatgg 420

ttctacctgc tgtgagctgc ccagtgggaa gtatggctgc tgccaatgcc caacgccacc 480

tgctgctccg atcacctgca ctgctgcccc aagacactgt gtgtgacctg atccagagta 540

agtgcctctc caaggagaac g 561

91

gaatcacctt tctggtttag ctagtacttt gtacagaaca atgaggtttc ccacagcgga 60

gtctccctgg gctctgtttg gctctcggta aggcaggcct acaccttttc ctctcctcta 120

tggagagggg aatatgcatt aaggtgaaaa gtcaccttcc aaaagtgaga aagggattcg 180

attgctgctt caggactgtg gaattatttg gaatgtttta caaatggttg ctacaaaaca 240

acaaaaaagg taattacaaa atgtgtacat cacaacatgc tttttaaaga cattatgcat 300

tgtgctcaca ttcccttaaa tgttgtttcc aaaggtgctc agcctctagc ccagctggat 360

tctccgggaa gaggcagaga cagtttggcg aaaaagacac agggaaggag ggggtggtga 420

aaggagaaag cagccttcca gttaaagatc agccctcagt taaaggtcag cttcccgcan 480

gctggcctca ngcggagtct gggtcagagg gaggagcagc agcagggtgg gactggggcg 540

t 541

92

551

Homo sapien

92

aaccggagcg cgagcagtag ctgggtgggc accatggctg ggatcaccac catcgaggcg 60

gtgaagcgca agatccaggt tctgcagcag caggcagatg atgcagagga gcgagctgag 120

cgcctccagc gagaagttga gggagaaagg cgggcccggg aacaggctga ggctgaggtg 180

gcctccttga accgtaggat ccagctggtt gaagaagagc tggaccgtgc tcaggagcgc 240

ctggccactg ccctgcaaaa gctggaagaa gctgaaaaag ctgctgatga gagtgagaga 300

ggtatgaagg ttattgaaaa ccgggcctta aaagatgaag aaaagatgga actccaggaa 360

atccaactca aagaagctaa gcacattgca gaagaggcag ataggaagta tgaagaggtg 420

gctcgtaagt tggtgatcat tgaaggagac ttggaacgca cagaggaacg agctgagctg 480

gcagagtccc gttgccgaga gatggatgag cagattagac tgatggacca gaacctgaag 540

tgtctgagtg c 551

93

531

Homo sapien

93

gagaacttgg cctttattgt gggcccagga gggcacaaag gtcaggaggc ccaagggagg 60

gatctggttt tctggatagc caggtcatag catgggtatc agtaggaatc cgctgtagct 120

gcacaggcct cacttgctgc agttccgggg agaacacctg cactgcatgg cgttgatgac 180

ctcgtggtac acgacagagc cattggtgca gtgcaagggc acgcgcatgg gctccgtcct 240

cgagggcagg cagcaggagc attgctcctg cacatcctcg atgtcaatgg agtacacagc 300

tttgctggca cactttccct ggcagtaatg aatgtccact tcctcttggg acttacaatc 360

tcccactttg atgtactgca ccttggctgt gatgtctttg caatcaggct cctcacatgt 420

gtcacagcag gtgcctggaa ttttcacgat tttgcctcct tcagccagac acttgtgttc 480

atcaaatggt gggcagcccg tgaccctctt ctcccagatg tactctcctc t 531

94

gcctggacct tgccggatca gtgccacaca gtgacttgct tggcaaatgg ccagaccttg 60

ctgcagagtc atcgtgtcaa ttgtgaccat ggaccccggc cttcatgtgc caacagccag 120

tctcctgttc gggtggagga gacgtgtggc tgccgctgga cctgcccttg tgtgtgcacg 180

ggcagttcca ctcggcacat cgtcaccttc gatgggcaga atttcaagct tactggtagc 240

tgctcctatg tcatctttca aaacaaggag caggacctgg aagtgctcct ccacaatggg 300

gcctgcagcc ccggggcaaa acaagcctgc atgaagtcca ttgagattaa gcatgctggc 360

gtctctgctg agctgcacag taacatggag atggcagtgg atgggagact ggtccttgcc 420

ccgtacgttg gtgaaaacat ggaagtcagc atctacggcg ctatcatgta tgaagtcagg 480

tttacccatc ttggccacat cctcacatac accgccncaa aacaacgagt t 531

95

605

Homo sapien

95

agatcaacct ctgctggtca ggaggaatgc cttccttgtc ttggatcttt gctttgacgt 60

tctcgatagt rwcaactkkr ytsramskma agkgyratgr wmttksywgw rasyktmwwm 120

rsgraraytt agacaycccm cctcwgagac gsagkaccar gtgcagaggt ggactctttc 180

tggatgttgt agtcagacag ggtgcgtcca tcttccagct gtttcccagc aaagatcaac 240

ctctgctgat caggagggat gccttcctta tcttggatct ttgccttgac attctcgatg 300

gtgtcactgg gctccacctc gagggtgatg gtcttaccag tcagggtctt cacgaagaty 360

tgcatcccac ctctgagacg gagcaccagg tgcagggtrg actctttctg gatgttgtag 420

tcagacaggg tgcgyccatc ttccagctgc tttccsagca aagatcaacc tctgctggtc 480

aggaggratg ccttccttgt cytggatctt tgcyttgacr ttctcratgg tgtcactcgg 540

ctccacttcg agagtgatgg tcttaccagt cagggtcttc acgaagatct gcatcccacc 600

tctaa 605

96

531

Homo sapien

96

aagtcacaaa cagacaaaga ttattaccag ctgcaagcta tattagaagc tgaacgaaga 60

gacagaggtc atgattctga gatgattgga gaccttcaag ctcgaattac atctttacaa 120

gaggaggtga agcatctcaa acataatctc gaaaaagtgg aaggagaaag aaaagaggct 180

caagacatgc ttaatcactc agaaaaggaa aagaataatt tagagataga tttaaactac 240

aaacttaaat cattacaaca acggttagaa caagaggtaa atgaacacaa agtaaccaaa 300

gctcgtttaa ctgacaaaca tcaatctatt gaagaggcaa agtctgtggc aatgtgtgag 360

atggaaaaaa agctgaaaga agaaagagaa gctcgagaga aggctgaaaa tcgggttgtt 420

cagattgaga aacagtgttc catgctagac gttgatctga agcaatctca gcagaaacta 480

gaacatttga ctggaaataa agaaaggatg gaggatgaag ttaagaatct a 531

97

cgcctccacc atgtccatca gggtgaccca gaagtcctac aaggtgtcca cctctggccc 60

ccgggccttc agcagccgct cctacacgag tgggcccggt tcccgcatca gctcctcgag 120

cttctcccga gtgggcagca gcaactttcg cggtggcctg ggcggcggct atggtggggc 180

cagcggcatg ggaggcatca ccgcagttac ggtcaaccag agcctgctga gcccccttgt 240

cctggaggtg gaccccaaca tccaggccgt gcgcacccag gagaaggagc agatcaagac 300

cctcaacaac aagtttgcct ccttcataga caaggtacgg ttcctggagc agcagaacaa 360

gatgctggag accaagtgga gcctcctgca gcagcagaag acggctcgaa gcaacatgga 420

caacatgttc gagagctaca tcaacarcct taggcggcag ctggagactc tgggccagga 480

gaagctgaag ctggaggcgg agcttggcaa catgcagggg ctggtggagg acttcaagaa 540

caagtatgag gatgagatca ataagcgtac agagatggag aacgaatttg tcctcatcaa 600

gaaggatgtg gatgaagctt acatgaacaa ggtagagctg gagtctcgcc tggaagggct 660

gaccgacgag atcaacttcc tcaggcagct gtatgaagag gagatccggg agctgcagtc 720

ccagatctcg gacacatctg tggtgctgtc catggacaac agccgctccc tggacatgga 780

cagcatcatt gctgaggtca aggcacagta cgaggatatt gccaaccgca gccgggctga 840

ggctgagagc atgtaccagg tcaagtatga ggagctgcag agcctggctg ggaagcacgg 900

ggatgacctg cggcgcacaa agactgagat ctctgagatg aacccggaac atcagcccgg 960

ctncaggctg agattgaggg cctcaaaggc caganggctt ncctggangn ccgccat 1017

98

561

Homo sapien

98

cccggagcca gccaacgagc ggaaaatggc agacaatttt tcgctccatg atgcgttatc 60

tgggtctgga aacccaaacc ctcaaggatg gcctggcgca tgggggaacc agcctgctgg 120

ggcagggggc tacccagggg cttcctatcc tggggcctac cccgggcagg cacccccagg 180

ggcttatcct ggacaggcac ctccaggcgc ctaccctgga gcacctggag cttatcccgg 240

agcacctgca cctggagtct acccagggcc acccagcggc cctggggcct acccatcttc 300

tggacagcca agtgccaccg gagcctaccc tgccactggc ccctatggcg cccctgctgg 360

gccactgatt gtgccttata acctgccttt gcctggggga gtggtgcctc gcatgctgat 420

aacaattctg ggcacggtga agcccaatgc aaacagaatt gctttagatt tccaaagagg 480

gaatgatgtt gccttccact ttaacccacg cttcaatgag aacaacagga gagtcattgg 540

ttgcaataca aagctggata a 561

99

636

Homo sapien

99

gggaatgcaa caactttatt gaaaggaaag tgcaatgaaa tttgttgaaa ccttaaaagg 60

ggaaacttag acaccccccc tcragcgmag kaccargtgc araggtggac tctttctgga 120

tgttgtagtc agacagggtr cgwccatctt ccagctgttt yccrgcaaag atcaacctct 180

gctgatcagg aggratgcct tccttatctt ggatctttgc cttgacattc tcgatggtgt 240

cactgggctc cacctcgagg gtgatggtct taccagtcag ggtcttcacg aagatytgca 300

tcccacctct gagacggagc accaggtgca gggtrgactc tttctggatg ttgtagtcag 360

acagggtgcg yccatcttcc agctgctttc csagcaaaga tcaacctctg ctggtcagga 420

ggratgcctt ccttgtcytg gatctttgcy ttgacrttct caatggtgtc actcggctcc 480

acttcgagag tgatggtctt accagtcagg gtcttcacga agatctgcat cccacctcta 540

agacggagca ccaggtgcag ggtggactct ttctggatgg ttgtagtcag acagggtgcg 600

tccatcttcc agctgtttcc cagcaaagat caacct 636

100

697

Homo sapien

100

aggttgatct ttgctgggaa acagctggaa gatggacgca ccctgtctga ctacaaccat 60

ccagaaagag tccaccctgc acctggtgct ccgtcttaga ggtgggatgc agatcttcgt 120

gaagaccctg actggtaaga ccatcactct cgaagtggag ccgagtgaca ccattgagaa 180

ygtcaargca aagatccarg acaaggaagg catycctcct gaccagcaga ggttgatctt 240

tgctsggaaa gcagctggaa gatggrcgca ccctgtctga ctacaacatc cagaaagagt 300

cyaccctgca cctggtgctc cgtctcagag gtgggatgca ratcttcgtg aagaccctga 360

ctggtaagac catcaccctc gaggtggagc ccagtgacac catcgagaat gtcaaggcaa 420

agatccaaga taaggaaggc atccctcctg atcagcagag gttgatcttt gctgggaaac 480

agctggaaga tggacgcacc ctgtctgact acaacatcca gaaagagtcc acctytgcac 540

ytggtmctbc gtctyagagg kgggrtgcaa atctwmgtkw agacactcac tkkyaagryy 600

atcamcmwtg akktcgakys castkwcact wtcrakaamg tyrwwgcawa gatccmagac 660

aaggaaggca ttcctcctga ccagcagagg ttgatct 697

101

451

Homo sapien

101

atggagtctc actctgtcga ccaggctgga gcgctgtggt gcgatatcgg ctcactgcag 60

tctccacttc ctgggttcaa gcgatcctcc tgcctcagcc tcccgagtag ctgggactac 120

aggcaggcgt caccataatt tttgtatttt tagtagagac atggtttcgc catgttggct 180

gggctggtct cgaactcctg acctcaagtg atctgtcctg gcctcccaaa gtgttgggat 240

tacaggcgaa agccaacgct cccggccagg gaacaacttt agaatgaagg aaatatgcaa 300

aagaacatca catcaaggat caattaatta ccatctatta attactatat gtgggtaatt 360

atgactattt cccaagcatt ctacgttgac tgcttgagaa gatgtttgtc ctgcatggtg 420

gagagtggag aagggccagg attcttaggt t 451

102

571

Homo sapien

102

agcgcggtct tccggcgcga gaaagctgaa ggtgatgtgg ccgccctcaa ccgacgcatc 60

cagctcgttg aggaggagtt ggacagggct caggaacgac tggccacggc cctgcagaag 120

ctggaggagg cagaaaaagc tgcagatgag agtgagagag gaatgaaggt gatagaaaac 180

cgggccatga aggatgagga gaagatggag attcaggaga tgcagctcaa agaggccaag 240

cacattgcgg aagaggctga ccgcaaatac gaggaggtag ctcgtaagct ggtcatcctg 300

gagggtgagc tggagagggc agaggagcgt gcggaggtgt ctgaactaaa atgtggtgac 360

ctggaagaag aactcaagaa tgttactaac aatctgaaat ctctggaggc tgcatctgaa 420

aagtattctg aaaaggagga caaatatgaa gaagaaatta aacttctgtc tgacaaactg 480

aaagaggctg agacccgtgc tgaatttgca gagagaacgg ttgcaaaact ggaaaagaca 540

attgatgacc tggaagagaa acttgcccag c 571

103

451

Homo sapien

103

gtgcacaggt cccatttatt gtagaaaata ataataatta cagtgatgaa tagctcttct 60

taaattacaa aacagaaacc acaaagaagg aagaggaaaa accccaggac ttccaagggt 120

gaagctgtcc cctcctccct gccaccctcc caggctcatt agtgtccttg gaaggggcag 180

aggactcaga ggggatcagt ctccaggggc cctgggctga agcgggtgag gcagagagtc 240

ctgaggccac agagctgggc aacctgagcc gcctctctgg ccccctcccc caccactgcc 300

caaacctgtt tacagcacct tcgcccctcc cctctaaacc cgtccatcca ctctgcactt 360

cccaggcagg tgggtgggcc aggcctcagc catactcctg ggcgcgggtt tcggtgagca 420

aggcacagtc ccagaggtga tatcaaggcc t 451

104

441

Homo sapien

104

gcaaggaact ggtctgctca cacttgctgg cttgcgcatc aggactggct ttatctcctg 60

actcacggtg caaaggtgca ctctgcgaac gttaagtccg tccccagcgc ttggaatcct 120

acggccccca cagccggatc ccctcagcct tccaggtcct caactcccgt ggacgctgaa 180

caatggcctc catggggcta caggtaatgg gcatcgcgct ggccgtcctg ggctggctgg 240

ccgtcatgct gtgctgcgcg ctgcccatgt ggcgcgtgac ggccttcatc ggcagcaaca 300

ttgtcacctc gcagaccatc tgggagggcc tatggatgaa ctgcgtggtg cagagcaccg 360

gccagatgca gtgcaaggtg tacgactcgc tgctggcact gccgcaggac ctgcaggcgg 420

cccgcgccct cgtcatcatc a 441

105

tgcaaaaggg acacaggggt tcaaaaataa aaatttctct tccccctccc caaacctgta 60

ccccagctcc ccgaccacaa cccccttcct cccccgggga aagcaagaag gagcaggtgt 120

ggcatctgca gctgggaaga gagaggccgg ggaggtgccg agctcggtgc tggtctcttt 180

ccaaatataa atacntgtgt cagaactgga aaatcctcca gcacccacca cccaagcact 240

ctccgttttc tgccggtgtt tggagagggg cggggggcag gggcgccagg caccggctgg 300

ctgcggtcta ctgcatccgc tgggtgtgca ccccgcgagc ctcctgctgc tcattgtaga 360

agagatgaca ctcggggtcc ccccggatgg tgggggctcc ctggatcagc ttcccggtgt 420

tggggttcac acaccagcac tccccacgct gcccgttcag agacatcttg cactgtttga 480

ggttgtacag gccatgcttg tcacagttg 509

106

571

Homo sapien

106

gggttggagg gactggttct ttatttcaaa aagacacttg tcaatattca gtatcaaaac 60

agttgcacta ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga 120

gtacatttta agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac 180

cagaaaatgg ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg 240

gactgcagag gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag 300

tttcaaaata atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc 360

actgactgat acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag 420

aaaagggtga tgagatgagt ttcacatggc taaatcagtg gcaaaaacac agtcttcttt 480

ctttctttct ttcaaggagg caggaaagca attaagtggt cacctcaaca taagggggac 540

atgatccatt ctgtaagcag ttgtgaaggg g 571

107

555

Homo sapien

107

caggaaccgg agcgcgagca gtagctgggt gggcaccatg gctgggatca ccaccatcga 60

ggcggtgaag cgcaagatcc aggttctgca gcagcaggca gatgatgcag aggagcgagc 120

tgagcgcctc cagcgagaag ttgagggaga aaggcgggcc cgggaacagg ctgaggctga 180

ggtggcctcc ttgaaccgta ggatccagct ggttgaagaa gagctggacc gtgctcagga 240

gcgcctggcc actgccctgc aaaagctgga agaagctgaa aaagctgctg atgagagtga 300

gagaggtatg aaggttattg aaaaccgggc cttaaaagat gaagaaaaga tggaactcca 360

ggaaatccaa ctcaaagaag ctaagcacat tgcagaagag gcagatagga agtatgaaga 420

ggtggctcgt aagttggtga tcattgaagg agacttggaa cgcacagagg aacgagctga 480

gctggcagag tcccgttgcc gagagatgga tgagcagatt agactgatgg accagaacct 540

gaagtgtctg agtgc 555

108

541

Homo sapien

108

atctacgtca tcaatcaggc tggagacacc atgttcaatc gagctaagct gctcaatatt 60

ggctttcaag aggccttgaa ggactatgat tacaactgct ttgtgttcag tgatgtggac 120

ctcattccga tggacgaccg taatgcctac aggtgttttt cgcagccacg gcacatttct 180

gttgcaatgg acaagttcgg gtttagcctg ccatatgttc agtattttgg aggtgtctct 240

gctctcagta aacaacagtt tcttgccatc aatggattcc ctaataatta ttggggttgg 300

ggaggagaag atgacgacat ttttaacaga ttagttcata aaggcatgtc tatatcacgt 360

ccaaatgctg tagtagggag gtgtcgaatg atccggcatt caagagacaa gaaaaatgag 420

cccaatcctc agaggtttga ccggatcgca catacaaagg aaacgatgcg cttcgatggt 480

ttgaactcac ttacctacaa ggtgttggat gtcagagata cccgttatat acccaaatca 540

c 541

109

411

Homo sapien

109

ctagacctct aattaaaagg cacaatcatg ctggagaatg aacagtctga ccccgagggc 60

cacagcgaat tttagggaag gaggcaaaga ggtgagaagg gaaaggaaag aaggaaggaa 120

ggagaacaat aagaactgga gacgttgggt gggtcaggga gtgtggtgga ggctcggaga 180

gatggtaaac aaacctgact gctatgagtt ttcaacccca tagtctaggg ccatgagggc 240

gtcagttctt ggtggctgag ggtccttcca cccagcccac ctgggggagt ggagtgggga 300

gttctgccag gtaagcagat gttgtctccc aagttcctga cccagatgtc tggcaggata 360

acgctgacct gttccctcaa caagggacct gaaagtaatt ttgctcttta c 411

110

451

Homo sapien

110

ccgaattcaa gcgtcaacga tccytccctt accatcaaat caattggcca ccaatggtac 60

tgaacctacg agtacaccga ctacgggcgg actaatcttc aactcctaca tacttccccc 120

attattccta gaaccaggcg acctgcgact ccttgacgtt gacaatcgag tagtactccc 180

gattgaagcc cccattcgta taataattac atcacaagac gtcttgcact catgagctgt 240

ccccacatta ggcttaaaaa cagatgcaat tcccggacgt ctaagccaaa ccactttcac 300

cgctacacga ccgggggtat actacggtca atgctctgaa atctgtggag caaaccacag 360

tttcatgccc atcgtcctag aattaattcc cctaaaaatc tttgaaatag ggcccgtatt 420

taccctatag caccccctct accccctcta g 451

111

541

Homo sapien

111

gctcttcaca cttttattgt taattctctt cacatggcag atacagagct gtcgtcttga 60

agaccaccac tgaccaggaa atgccacttt tacaaaatca tccccccttt tcatgattgg 120

aacagttttc ctgaccgtct gggagcgttg aagggtgacc agcacatttg cacatgcaaa 180

aaaggagtga ccccaaggcc tcaaccacac ttcccagagc tcaccatggg ctgcaggtga 240

cttgccaggt ttggggttcg tgagctttcc ttgctgctgc ggtggggagg ccctcaagaa 300

ctgagaggcc ggggtatgct tcatgagtgt taacatttac gggacaaaag cgcatcatta 360

ggataaggaa cagccacagc acttcatgct tgtgagggtt agctgtagga gcgggtgaaa 420

ggattccagt ttatgaaaat ttaaagcaaa caacggtttt tagctgggtg ggaaacagga 480

aaactgtgat gtcggccaat gaccaccatt tttctgccca tgtgaaggtc cccatgaaac 540

c 541

112

521

Homo sapien

112

caagcgcttg gcgtttggac ccagttcagt gaggttcttg ggttttgtgc ctttggggat 60

tttggtttga cccaggggtc agccttagga aggtcttcag gaggaggccg agttcccctt 120

cagtaccacc cctctctccc cactttccct ctcccggcaa catctctggg aatcaacagc 180

atattgacac gttggagccg agcctgaaca tgcccctcgg ccccagcaca tggaaaaccc 240

ccttccttgc ctaaggtgtc tgagtttctg gctcttgagg catttccaga cttgaaattc 300

tcatcagtcc attgctcttg agtctttgca gagaacctca gatcaggtgc acctgggaga 360

aagactttgt ccccacttac agatctatct cctcccttgg gaagggcagg gaatggggac 420

ggtgtatgga ggggaaggga tctcctgcgc ccttcattgc cacacttggt gggaccatga 480

acatctttag tgtctgagct tctcaaatta ctgcaatagg a 521

113

568

Homo sapien

113

agcgtcaaat cagaatggaa aagactcaaa accatcatca acaccaagat caaaaggaca 60

agratccttc aagaaacagg aaaaaactcc taaaacacca aaaggaccta gttctgtaga 120

agacattaaa gcaaaaatgc aagcaagtat agaaaaaggt ggttctcttc ccaaagtgga 180

agccaaattc atcaattatg tgaagaattg cttccggatg actgaccaag aggctattca 240

agatctctgg cagtggagga agtctcttta agaaaatagt ttaaacaatt tgttaaaaaa 300

ttttccgtct tatttcattt ctgtaacagt tgatatctgg ctgtcctttt tataatgcag 360

agtgagaact ttccctaccg tgtttgataa atgttgtcca ggttctattg ccaagaatgt 420

gttgtccaaa atgcctgttt agtttttaaa gatggaactc caccctttgc ttggttttaa 480

gtatgtatgg aatgttatga taggacatag tagtagcggt ggtcagacat ggaaatggtg 540

ggsmgacaaa aatatacatg tgaaataa 568

114

483

Homo sapien

114

tccgaattcc aagcgaatta tggacaaacg attcctttta gaggattact tttttcaatt 60

tcggttttag taatctaggc tttgcctgta aagaatacaa cgatggattt taaatactgt 120

ttgtggaatg tgtttaaagg attgattcta gaacctttgt atatttgata gtatttctaa 180

ctttcatttc tttactgttt gcagttaatg ttcatgttct gctatgcaat cgtttatatg 240

cacgtttctt taattttttt agattttcct ggatgtatag tttaaacaac aaaaagtcta 300

tttaaaactg tagcagtagt ttacagttct agcaaagagg aaagttgtgg ggttaaactt 360

tgtattttct ttcttataga ggcttctaaa aaggtatttt tatatgttct ttttaacaaa 420

tattgtgtac aacctttaaa acatcaatgt ttggatcaaa acaagaccca gcttattttc 480

tgc 483

115

521

Homo sapien

115

tgtggtggcg cgggctgagg tggaggccca ggactctgac cctgcccctg ccttcagcaa 60

ggcccccggc agcgccggcc actacgaact gccgtgggtt gaaaaatata ggccagtaaa 120

gctgaatgaa attgtcggga atgaagacac cgtgagcagg ctagaggtct ttgcaaggga 180

aggaaatgtg cccaacatca tcattgcggg ccctccagga accggcaaga ccacaagcat 240

tctgtgcttg gcccgggccc tgctgggccc agcactcaaa gatgccatgt tggaactcaa 300

tgcttcaaat gacaggggca ttgacgttgt gaggaataaa attaaaatgt ttgctcaaca 360

aaaagtcact cttcccaaag gccgacataa gatcatcatt ctggatgaag cagacagcat 420

gaccgacgga gcccagcaag ccttgaggag aaccatggaa atctactcta aaaccactcg 480

ttcgcccttg cttgtaatgc ttcggataag atcatcgagc c 521

116

501

Homo sapien

116

ctttgcaaag cttttatttc atgtctgcgg catggaatcc acctgcacat ggcatcttag 60

ctgtgaagga gaaagcagtg cacgagaagg aatgagtggg cggaaccaac ggcctccaca 120

agctgccttc cagcagcctg ccaaggccat ggcagagaga gactgcaaac aaacacaagc 180

aaacagagtc tcttcacagc tggagtctga aagctcatag tggcatgtgt gaatctgaca 240

aaattaaaag tgtgcatagt ccattacatg cataaaacac taataataat cctgtttaca 300

cgtgactgca gcaggcaggt ccagctccac cactgccctc ctgccacatc acatcaagtg 360

ccatggttta gagggttttt catatgtaat tcttttattc tgtaaaaggt aacaaaatat 420

acagaacaaa actttccctt tttaaaacta atgttacaaa tctgtattat cacttggata 480

taaatagtat ataagctgat c 501

117

caagggatat atgttgaggg tacrgrgtga cactgaacag atcacaaagc acgagaaaca 60

ttagttctct ccctccccag cgtctccttc gtctccctgg ttttccgatg tccacagagt 120

gagattgtcc ctaagtaact gcatgatcag agtgctgkct ttataagact cttcattcag 180

cgtatccaat tcagcaattg cttcatcaaa tgccgttttt gccaggctac aggccttttc 240

aggagagttt agaatctcat agtaaaagac tgagaaattt agtgccagac caagacgaat 300

tgggtgtgta ggctgcattn ctttcttact aatttcaaat gcttcctggt aagcctgctg 360

ggagttcgac acaagtggtt tgtttgttgc tccagatgcc acttcagaaa gatacctaaa 420

ataatctcct ttcattttca aagtagaaca c 451

118

501

Homo sapien

118

tccggagccg gggtagtcgc cgccgccgcc gccggtgcag ccactgcagg caccgctgcc 60

gccgcctgag tagtgggctt aggaaggaag aggtcatctc gctcggagct tcgctcggaa 120

gggtctttgt tccctgcagc cctcccacgg gaatgacaat ggataaaagt gagctggtac 180

agaaagccaa actcgctgag caggctgagc gatatgatga tatggctgca gccatgaagg 240

cagtcacaga acaggggcat gaactctcca acgaagagag aaatctgctc tctgttgcct 300

acaagaatgt ggtaaggccg cccgccgctc ttcctggcgt gtcatctcca gcattgagca 360

gaaaacagag aggaatgaga agaagcagca gatgggcaaa gagtaccgtg agaagataga 420

ggcagaactg caggacatct gcaatgatgt tctggagctt gttggacaaa tatcttattc 480

caatgctaca caacccagaa a 501

119

391

Homo sapien

119

aaaaagcagc argttcaaca caaaatagaa atctcaaatg taggatagaa caaaaccaag 60

tgtgtgaggg gggaagcaac agcaaaagga agaaatgaga tgttgcaaaa aagatggagg 120

agggttcccc tctcctctgg ggactgactc aaacactgat gtggcagtat acaccattcc 180

agagtcaggg gtgttcattc ttttttggga gtaagaaaag gtggggatta agaagacgtt 240

tctggaggct tagggaccaa ggctggtctc tttcccccct cccaaccccc ttgatccctt 300

tctctgatca ggggaaagga gctcgaatga gggaggtaga gttggaaagg gaaaggattc 360

cacttgacag aatgggacag actccttccc a 391

120

tggcaatagc acagccatcc aggagctctt cargcgcatc tcggagcagt tcactgccat 60

gttccgccgg aaggccttcc tccactggta cacaggcgag ggcatggacg agatggagtt 120

caccgaggct gagagcaaca tgaacgacct cgtctctgag tatcaagcag taccaggatg 180

ccaccgcaga agaggaggag gatttcggtg aggaggccga agaggaggcc taaggcagag 240

cccccatcac ctcaggcttc tcagttccct tagccgtctt actcaactgc ccctttcctc 300

tccctcagaa tttgtgtttg ctgcctctat cttgtttttt gttttttctt ctgggggggt 360

ctagaacagt gcctggcaca tagtaggcgc tcaataaata cttggttgnt gaatgtctcc 420

t 421

121

206

Homo sapien

121

agctggcgct agggctcggt tgtgaaatac agcgtrgtca gcccttgcgc tcagtgtaga 60

aacccacgcc tgtaaggtcg gtcttcgtcc atctgctttt ttctgaaata cactaagagc 120

agccacaaaa ctgtaacctc aaggaaacca taaagcttgg agtgccttaa tttttaacca 180

gtttccaata aaacggttta ctacct 206

122

131

Homo sapien

122

ggagatgaag atgaggaagc tgagtcagct acgggcargc gggcagctga agatgatgag 60

gatgacgatg tcgataccaa gaagcagaag accgacgagg atgactagac agcaaaaaag 120

gaaaagttaa a 131

123

gatgaaaatt aaatacttaa attaatcaaa aggcactacg ataccaccta aaacctactg 60

cctcagtggc agtakgctaa kgaagatcaa gctacagsac atyatctaat atgaatgtta 120

gcaattacat akcargaagc atgtttgctt tccagaagac tatggnacaa tggtcattwg 180

ggcccaagag gatatttggc cnggaaagga tcaagataga tnaangtaaa g 231

124

gagtagcaac gcaaagcgct tggtattgag tctgtgggsg acttcggttc cggtctctgc 60

agcagccgtg atcgcttagt ggagtgctta gggtagttgg ccaggatgcc gaatatcaaa 120

atcttcagca ggcagctccc accaggactt atctcasaaa attgctgacc gcctgggcct 180

ggagctaggc aaggtggtga ctaagaaatt cagcaaccag gagacctgtg tggaaattgg 240

tgaaagtgta ccgtggagag gatgtctaca ttgttcagag tggntgtggc gaaatcaatg 300

acaatttaat ggagcttttg atcatgatta atgcctgcaa gattgcttca gccagccggg 360

ttactgcagt catcccatgc ttcccttatg ccccggcagg ataagaaaga tnagagccgg 420

gccgccaatc tcagccaagc ttggtgcaaa tatgctatct gtagcagtgc agatcatatt 480

atcaccatgg acctacatgc ttctcaaatt canggctttt t 521

125

atgcaaaagg ggacacaggg ggttcaaaaa taaaaatttc tcttccccct ccccaaacct 60

gtaccccagc tccccgacca caaccccctt cctcccccgg ggaaagcaag aaggagcagg 120

tgtggcatct gcagctggga agagagaggc cggggaggtg ccgagctcgg tgctggtctc 180

tttccaaata taaatacgtg tgtcagaact ggaaaatcct ccagcaccca ccacccaagc 240

actctccgtt ttctgccggt gtttggagag gggcggnggg caggggcgcc aggcaccggc 300

tggctgcggt ctactgcatc cgctgggtgt gcaccccgcg a 341

126

aggttggaga aggtcatgca ggtgcagatt gtccaggskc agccacaggg tcaagcccaa 60

caggcccaga gtggcactgg acagaccatg caggtgatgc agcagatcat cactaacaca 120

ggagagatcc agcagatccc ggtgcagctg aatgccggcc agctgcagta tatccgctta 180

gcccagcctg tatcaggcac tcaagttgtg cagggacaga tccagacact tgccaccaat 240

gctcaacaga ttacacagac agaggtccag caaggacagc agcagttcaa gccagttcac 300

aagatggaca gcagctctac cagatccagc aagtcaccat gcctgcgggc cangacctcg 360

ccagcccatg ttcatccagt caagccaacc agcccttcna cgggcaggcc ccccaggtga 420

ccggcgactg aagggcctga gctggcaagg ccaangacac ccaacacaat ttttgccata 480

cagcccccag gcaatgggca cagcctttct tcccagagga c 521

127

351

Homo sapien

127

tgagatttat tgcatttcat gcagcttgaa gtccatgcaa aggrgactag cacagttttt 60

aatgcattta aaaaataaaa gggaggtggg cagcaaacac acaaagtcct agtttcctgg 120

gtccctggga gaaaagagtg tggcaatgaa tccacccact ctccacaggg aataaatctg 180

tctcttaaat gcaaagaatg tttccatggc ctctggatgc aaatacacag agctctgggg 240

tcagagcaag ggatggggag aggaccacga gtgaaaaagc agctacacac attcacctaa 300

ttccatctga gggcaagaac aacgtggcaa gtcttggggg tagcagctgt t 351

128

521

Homo sapien

128

tccagacatg ctcctgtcct aggcggggag caggaaccag acctgctatg ggaagcagaa 60

agagttaagg gaaggtttcc tttcattcct gttccttctc ttttgctttt gaacagtttt 120

taaatatact aatagctaag tcatttgcca gccaggtccc ggtgaacagt agagaacaag 180

gagcttgcta agaattaatt ttgctgtttt tcaccccatt caaacagagc tgccctgttc 240

cctgatggag ttccattcct gccagggcac ggctgagtaa cacgaagcca ttcaagaaag 300

gcgggtgtga aatcactgcc accccatgga cagacccctc actcttcctt cttagccgca 360

gcgctactta ataaatatat ttatactttg aaattatgat aaccgatttt tcccatgcgg 420

catcctaagg gcacttgcca gctcttatcc ggacagtcaa gcactgttgt tggacaacag 480

ataaaggaaa agaaaaagaa gaaaacaacc gcaacttctg t 521

129

521

Homo sapien

129

tgagacggac cactggcctg gtcccccctc atktgctgtc gtaggacctg acatgaaacg 60

cagatctagt ggcagagagg aagatgatga ggaacttctg agacgtcggc agcttcaaga 120

agagcaatta atgaagctta actcaggcct gggacagttg atcttgaaag aagagatgga 180

gaaagagagc cgggaaaggt catctctgtt agccagtcgc tacgattctc ccatcaactc 240

agcttcacat attccatcat ctaaaactgc atctctccct ggctatggaa gaaatgggct 300

tcaccggcct gtttctaccg acttcgctca gtataacagc tatggggatg tcagcggggg 360

agtgcgagat taccagacac ttccagatgg ccacatgcct gcaatgagaa tggaccgagg 420

agtgtctatg cccaacatgt tggaaccaaa gatatttcca tatgaaatgc tcatggtgac 480

caacagaggg ccgaaaccaa atctcagaga ggtggacaga a 521

130

270

Homo sapien

130

tcactttatt tttcttgtat aaaaacccta tgttgtagcc acagctggag cctgagtccg 60

ctgcacggag actctggtgt gggtcttgac gaggtggtca gtgaactcct gatagggaga 120

cttggtgaat acagtctcct tccagaggtc gggggtcagg tagctgtagg tcttagaaat 180

ggcatcaaag gtggccttgg cgaagttgcc cagggtggca gtgcagcccc gggctgaggt 240

gtagcagtca tcgataccag ccatcatgag 270

131

341

Homo sapien

131

ctggaatata gacccgtgat cgacaaaact ttgaacgagg ctgactgtgc caccgtcccg 60

ccagccattc gctcctactg atgagacaag atgtggtgat gacagaatca gcttttgtaa 120

ttatgtataa tagctcatgc atgtgtccat gtcataactg tcttcatacg cttctgcact 180

ctggggaaga aggagtacat tgaagggaga ttggcaccta gtggctggga gcttgccagg 240

aacccagtgg ccagggagcg tggcacttac ctttgtccct tgcttcattc ttgtgagatg 300

ataaaactgg gcacagctct taaataaaat ataaatgaac a 341

132

tgaatgggga ggagctgacc caggaaatgg agcttgngga gaccaggcct gcaggggatg 60

gaaccttcca gaagtgggca tctgtggtgg tgcctcttgg gaaggagcag aagtacacat 120

gccatgtgga acatgagggg ctgcctgagc ccctcaccct gagatggggc aaggaggagc 180

ctccttcatc caccaagact aacacagtaa tcattgctgt tccggttgtc cttggagctg 240

tggtcatcct tggagctgtg atggcttttg tgatgaagag gaggagaaac acaggtggaa 300

aaggagggga ctatgctctg gctccaggct cccagagctc tgatatgtct ctcccagatt 360

gtaaagtgtg aagacagctg cctggtgtgg acttggtgac agacaatgtc ttcacacatc 420

tcctgtgaca tccagagacc tcagttctct ttagtcaagt gtctgatgtt ccctgtgagt 480

ctgcgggctc aaagtgaaga actgtggagc ccagtccacc cctgcacacc aggaccctat 540

ccctgcactg ccctgtgttc ccttccacag ccaaccttgc tgctccagcc aaacattggt 600

ggacatctgc agcctgtcag ctccatgcta ccctgacctt caactcctca cttccacact 660

gagaataata atttgaatgt gggtggctgg agagatggct cagcgctgac tgctcttcca 720

aaggtcctga gttcaaatcc cagcaaccac atggtggctc acaaccatct gtaatgggat 780

ctaataccct cttctgcagt gtctgaagac asctacagtg tacttacata taataataaa 840

taag 844

133

601

Homo sapien

133

ggccgggcgc gcgcgccccc gccacacgca cgccgggcgt gccagtttat aaagggagag 60

agcaagcagc gagtcttgaa gctctgtttg gtgctttgga tccatttcca tcggtcctta 120

cagccgctcg tcagactcca gcagccaaga tggtgaagca gatcgagagc aagactgctt 180

ttcaggaagc cttggacgct gcaggtgata aacttgtagt agttgacttc tcagccacgt 240

ggtgtgggcc ttgcaaaatg atcaagcctt tctttcattc cctctctgaa aagtattcca 300

acgtgatatt ccttgaagta gatgtggatg actgtcagga tgttgcttca gagtgtgaag 360

tcaaatgcat gccaacattc cagtttttta agaagggaca aaaggtgggt gaattttctg 420

gagccaataa ggaaaagctt gaagccacca ttaatgaatt agtctaatca tgttttctga 480

aaatataacc agccattggc tatttaaaac ttgtaatttt tttaatttac aaaaatataa 540

aatatgaaga cataaacccm gttgccatct gcgtgacaat aaaacattaa tgctaacact 600

t 601

134

421

Homo sapien

134

tcacataaga aatttaagca agttacrcta tcttaaaaaa cacaacgaat gcattttaat 60

agagaaaccc ttccctccct ccacctccct cccccaccct cctcatgaat taagaatcta 120

agagaagaag taaccataaa accaagtttt gtggaatcca tcatccagag tgcttacatg 180

gtgattaggt taatattgcc ttcttacaaa atttctattt taaaaaaaat tataaccttg 240

attgcttatt acaaaaaaat tcagtacaaa agttcaatat attgaaaaat gcttttcccc 300

tccctcacag caccgtttta tatatagcag agaataatga agagattgct agtctagatg 360

gggcaatctt caaattacac caagacgcac agtggtttat ttaccctccc cttctcataa 420

g 421

135

511

Homo sapien

135

ggaaaggatt caagaattag aggacttgct tgctrragaa aaagacaact ctcgtcgcat 60

gctgacagac aaagagagag agatggcgga aataagggat caaatgcagc aacagctgaa 120

tgactatgaa cagcttcttg atgtaaagtt agccctggac atggaaatca gtgcttacag 180

gaaactctta gaaggcgaag aagagaggtt gaagctgtct ccaagccctt cttcccgtgt 240

gacagtatcc cgagcatcct caagtcgtag tgtaccgtac aactagagga aagcggaaga 300

gggttgatgt ggaagaatca gaggcgaagt agtagtgtta gcatctctca ttccgcctca 360

accactggaa atgtttgcat cgaagaaatt gatgttgatg ggaaatttat cccgcttgaa 420

gaacacttct gaacaggatc aaccaatggg aaggcttggg agatgatcag aaaaattgga 480

gacacatcag tcagttataa atatacctca a 511

136

341

Homo sapien

136

catgggtttc accaggttgg ccaggctgct cttgaactsc tgacctcagg tgatccaccc 60

gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg gcccccaaag 120

ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca taactgacgt 180

gactgccagc aagctcagtc actccgtggt ctttttctct ttccagttct tctctctctc 240

ttcaagttct gcctcagtga aagctgcagg tccccagtta agtgatcagg tgagggttct 300

ttgaacctgg ttctatcagt cgaattaatc cttcatgatg g 341

137

551

Homo sapien

137

gatgtgttgg accctctgtg tcaaaaaaaa cctcacaaag aatcccctgc tcattacaga 60

agaagatgca tttaaaatat gggttatttt caacttttta tctgaggaca agtatccatt 120

aattattgtg tcagaagaga ttgaatacct gcttaagaag cttacagaag ctatgggagg 180

aggttggcag caagaacaat ttgaacatta taaaatcaac tttgatgaca gtaaaaatgg 240

cctttctgca tgggaactta ttgagcttat tggaaatgga cagtttagca aaggcatgga 300

ccggcagact gtgtctatgg caattaatga agtctttaat gaacttatat tagatgtgtt 360

aaagcagggt tacatgatga aaaagggcca cagacggaaa aactggactg aaagatggtt 420

tgtactaaaa cccaacataa tttcttacta tgtgagtgag gatctgaagg ataagaaagg 480

agacattctc ttggatgaaa attgctgtgt agaagtcctt gcctgacaaa agatggaaag 540

aaatgccttt t 551

138

gactggttct ttatttcaaa aagacacttg tcaatattca gtrtcaaaac agttgcacta 60

ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga gtacatttta 120

agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac cagaaaatgg 180

ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg gactgcagag 240

gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag tttcaaaata 300

atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc actgactgat 360

acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag aaaagggtga 420

tgagatgaag tttcacatgg ctaaatcagt ggcaaaaaca cagtcttctt tctttctttc 480

tttcaaggan gcaggaaagc aattaagtgg tcaccttaac ataaggggga c 531

139

tgggtgggca ccatggctgg gatcaccacc atcgaggcgg tgaagcgcaa gatccaggtt 60

ctgcagcagc aggcagatga tgcagaggag cgagctgagc gcctccagcg agaagttgag 120

ggagaaaggc gggcccggga acaggctgag gctgaggtgg cctccttgaa ccgtaggatc 180

cagctggttg aagaagagct ggaccgtgct caggagcgcc tggccactgc cctgcaaaag 240

ctggaagaag ctgaaaaagc tgctgatgag agtgagagag gtatgaaggt tattgaaaac 300

cgggccttaa aagatgaaga aaagatggaa ctccaggaaa tccaactcaa agaagctaag 360

cacattgcag aagaggcaga taggaagtat gaagaggtgg ctcgtaagtt ggtgatcatt 420

gaaggagact tggaaccgca cagaaggaac gagcttgagc ttggcaaaag tcccgttgcc 480

cagagatggg atgaaccaga ttagactgat ggaccanaac c 521

140

aggggcngcg ggtgcgtggg ccactgggtg accgacttag cctggccaga ctctcagcac 60

ctggaagcgc cccgagagtg acagcgtgag gctgggaggg aggacttggc ttgagcttgt 120

taaactctgc tctgagcctc cttgtcgcct gcatttagat ggctcccgca aagaagggtg 180

gcgagaagaa aaagggccgt tctgccatca acgaagtggt aacccgagaa tacaccatca 240

acattcacaa gcgcatccat ggagtgggct tcaagaagcg tgcacctcgg gcactcaaag 300

agattcggaa atttgccatg aaggagatgg gaactccaga tgtgcgcatt gacaccaggc 360

tcaacaaagc tgtctgggcc aaaggaataa ggaatgtgcc ataccgaatc cggtgtgcgg 420

ctgtccagaa aacgtaatga ggatgaagat tcaccaaata agctatatac tttggttacc 480

tatgtacctg ttaccacttt caaaaatcta cagacagtca atgtggatga gaactaatcg 540

ctgatcgtca gatcaaataa agttataaaa t 571

141

531

Homo sapien

141

tcgggagcca cacttggccc tcttcctctc caaagsgcca gaacctcctt ctctttggag 60

aatggggagg cctcttggag acacagaggg tttcaccttg gatgacctct agagaaattg 120

cccaagaagc ccaccttctg gtcccaacct gcagacccca cagcagtcag ttggtcaggc 180

cctgctgtag aaggtcactt ggctccattg cctgcttcca accaatgggc aggagagaag 240

gcctttattt ctcgcccacc cattcctcct gtaccagcac ctccgttttc agtcagtgtt 300

gtccagcaac ggtaccgttt acacagtcac ctcagacaca ccatttcacc tcccttgcca 360

agctgttagc cttagagtga ttgcagtgaa cactgtttac acaccgtgaa tccattccca 420

tcagtccatt ccagttggca ccagcctgaa ccatttggta cctggtgtta actggagtcc 480

tgtttacaag gtggagtcgg ggcttgctga cttctcttca tttgagggca c 531

142

acctagacag aaggtgggtg agggaggact ggtaggaggc tgaggcaatt ccttggtagt 60

ttgtcctgaa accctactgg agaagtcagc atgaggcacc tactgagaga agtgcccaga 120

aactgctgac tgcatctgtt aagagttaac agtaaagagg tagaagtgtg tttctgaatc 180

agagtggaag cgtctcaagg gtcccacagt ggaggtccct gagctacctc ccttccgtga 240

gtgggaagag tgaagcccat gaagaactga gatgaagcaa ggatggggtt cctgggctcc 300

aggcaagggc tgtgctctct gcagcaggga gccccacgag tcagaagaaa agaactaatc 360

atttgttgca agaaaccttg cccggatact agcggaaaac tggaggcggn ggtgggggca 420

caggaaagtg gaagtgattt gatggagagc agagaagcct atgcacagtg gccgagtcca 480

cttgtaaagt g 491

143

515

Homo sapien

143

ttcaagcaat tgtaacaagt atatgtagat tagagtgagc aaaatcatat acaattttca 60

tttccagttg ctattttcca aattgttctg taatgtcgtt aaaattactt aaaaattaac 120

aaagccaaaa attatattta tgacaagaaa gccatcccta cattaatctt acttttccac 180

tcaccggccc atctccttcc tctttttcct aactatgcca ttaaaactgt tctactgggc 240

cgggcgtgtg gctcatgcct gtaatcccag cattttggga ggccaaggca ggcggatcat 300

gaggtcaaga gattgagacc atcctggcca acatggtgaa accccgcctc gactaagaat 360

acaaaaatta gctgggcatg gtggcgcatg cctgtagtct cagctactcg ggaggctgag 420

gcagaagaat cgcttgaacc cgggaggcag aggatgcagt gagccccgat cgcgccactg 480

cactctagcc tgggcgacag actgagactc tgctc 515

144

340

Homo sapien

144

tgtgccagtc tacaggccta tcagcagcga ctccttcagc aacagatggg gtcccctgtt 60

cagcccaacc ccatgagccc ccagcagcat atgctcccaa atcaggccca gtccccacac 120

ctacaaggcc agcagatccc taattctctc tccaatcaag tgcgctctcc ccagcctgtc 180

ccttctccac ggccacagtc ccagcccccc cactccagtc cttccccaag gatgcagcct 240

cagccttctc cacaccacgt ttccccacag acaagttccc cacatcctgg actggtagtt 300

gcccaggcca accccatgga acaagggcat tttgccagcc 340

145

630

Homo sapien

145

tgtaaaaact tgtttttaat tttgtataaa ataaaggtgg tccatgccca cgggggctgt 60

aggaaatcca agcagaccag ctggggtggg gggatgtagc ctacctcggg ggactgtctg 120

tcctcaaaac gggctgagaa ggcccgtcag gggcccaggt cccacagaga ggcctgggat 180

actcccccaa cccgaggggc agactgggca gtggggagcc cccatcgtgc cccagaggtg 240

gccacaggct gaaggagggg cctgaggcac cgcagcctgc aacccccagg gctgcagtcc 300

actaactttt tacagaataa aaggaacatg gggatgggga aaaaagcacc aggtcaggca 360

gggcccgagg gccccagatc ccaggagggc caggactcag gatgccagca ccaccctagc 420

agctcccaca gctcctggca caggaggccg ccacggattg gcacaggccg ctgctggcca 480

tcacgccaca tttggagaac ttgtcccgac agaggtcagc tcggaggagc tcctcgtggg 540

cacacactgt acgaacacag atctccttgt taatgacgta cacacggcgg aggctgcggg 600

gacagggcac gggaggtctc agccccactt 630

146

521

Homo sapien

146

atggctgctg gatttaggtg gtaatagggg ctgtgggcca taaatctgaa gccttgagaa 60

ccttgggtct ggagagccat gaagagggaa ggaaaagagg gcaagtcctg aacctaacca 120

atgacctgat ggattgctcg accaagacac agaagtgaag tctgtgtctg tgcacttccc 180

acagactgga gtttttggtg ctgaatagag ccagttgcta aaaaattggg ggtttggtga 240

agaaatctga ttgttgtgtg tattcaatgt gtgattttaa aaataaacag caacaacaat 300

aaaaaccctg actggctgtt ttttccctgt attctttaca actatttttt gaccctctga 360

aaattattat acttcaccta aatggaagac tgctgtgttt gtggaaattt tgtaattttt 420

taatttattt tattctctct cctttttatt ttgcctgcag aatccgttga gagactaata 480

aggcttaata tttaattgat ttgtttaata tgtatataaa t 521

147

562

Homo sapien

147

ggcatgcgag cgcactcggc ggacgcaagg gcggcgggga gcacacggag cactgcaggc 60

gccgggttgg gacagcgtct tcgctgctgc tggatagtcg tgttttcggg gatcgaggat 120

actcaccaga aaccgaaaat gccgaaacca atcaatgtcc gagttaccac catggatgca 180

gagctggagt ttgcaatcca gccaaataca actggaaaac agctttttga tcaggtggta 240

aagactatcg gcctccggga agtgtggtac tttggcctcc actatgtgga taataaagga 300

tttcctacct ggctgaagct ggataagaag gtgtctgccc aggaggtcag gaaggagaat 360

cccctccagt tcaagttccg ggccaaagtt ctaccctgaa gatgtggctg aggagctcat 420

ccaggacatc acccagaaac ttttcttcct tcaagtgaag gaaggaatcc ttagcgatga 480

gatctactgc cccccttgar actgccgtgc tcttggggtc ctacgcttgt gcatgccaag 540

tttggggact accaccaaga ag 562

148

820

Homo sapien

148

gaaggagtcg ggatactcag cattgatgca ccccaatttc aaagcggcat tcttcggcag 60

gtctctggga caatctctag ggtcactacc tggaaactcg ttagggtaca actgaatgct 120

gaaaggaaag aacacctgca gaaccggaca gaaattcacc ccggcgatca gctgattgat 180

ctcggtcgac cagaagtcat ggctaaagat gacgaggacg ttgtcaattc cctgggcttt 240

tcgaagtgag tccagcagca gtctgaggta ttcgggccgg ttatgcacct ggaccaccag 300

caccagctcc cggggggccc aggtgccagc cttatctaca ttcctcaggg tctgatcaaa 360

gttcagctgg tacaccaggg accggtaccg cagcgtcagg ttgtccgctc gggctggggg 420

accgccggga ccagggaagc cgccgacacg ttggagaccc tgcggatgcc cacagccaca 480

gaggggtggt ccccaccgcg gccgccggca ccccgcgcgg gttcggcgtc cagcaacggt 540

ggggcgaggg cctcgttctt cctttgtcgc ccattgctgc tccagaggac gaagccgcag 600

gcggccacca cgagcgtcag gattagcacc ttccgtttgt agatgcggaa cctcatggtc 660

tccagggccg ggagcgcagc tacagctcga gcgtcggcgc cgccgctagg agccgcggct 720

cggcttcgtc tccgtcctct ccattcagca ccacgggtcc cggaaaaagc tcagccscgg 780

tcccaaccgc accctagctt cgttacctgc gcctcgcttg 820

149

501

Homo sapien

149

cagattttta tttgcagtcg tcactggggc cgtttcttgc tgcttatttg tctgctagcc 60

tgctcttcca gctgcatggc caggcgcaag gccttgatga catctcgcag ggctgagaaa 120

tgcttggctt gctgggccag agcagattcc gctttgttca caaaggtctc caggtcatag 180

tctggctgct cggtcatctc agagagctca agccagtctg gtccttgctg tatgatctcc 240

ttgagctctt ccatagcctt ctcctccagc tccctgatct gagtcatggc ttcgttaaag 300

ctggacatct gggaagacag ttcctcctct tccttggata aattgcctgg aatcagcgcc 360

ccgttagagc aggcttccat ctcttctgtt tccatttgaa tcaactgctc tccactgggc 420

ccactgtggg ggctcagctc cttgaccctg ctgcatatct taagggtgtt taaaggatat 480

tcacaggagc ttatgcctgg t 501

150

ctcctcttgg tacatgaacc caagttgaaa gtggacttaa caaagtatct ggagaaccaa 60

gcattctgct ttgactttgc atttgatgaa acagcttcga atgaagttgt ctacaggttc 120

acagcaaggc cactggtaca gacaatcttt gaaggtggaa aagcaacttg ttttgcatat 180

ggccagacag gaagtggcaa gacacatact atgggcggag acctctctgg gaaagcccag 240

aatgcatcca aagggatcta tgccatggcc ttccgggacg tcttcttctg aagaatcaac 300

cctgctaccg gaagttgggc ctggaagtct atgtgacatt cttcgagatc tacaatggga 360

agctgtttga cctgctcaac aagaaggcca agcttgcgcg tgctggaaga cggcaagcaa 420

caggtgcaag tggtgggggc ttgcaggaac atctggntaa ctctgcttga tgatggcant 480

caagatgatc gacatgggca gcgcctgcag a 511

151

566

Homo sapien

151

tcccgaattc aagcgacaaa ttggawagtg aaatggaaga tgcctatcat gaacatcagg 60

caaatctttt gcgccaagat ctgatgagac gacaggaaga attaagacgc atggaagaac 120

ttcacaatca agaaatgcag aaacgtaaag aaatgcaatt gaggcaagag gaggaacgac 180

gtagaagaga ggaagagatg atgattcgtc aacgtgagat ggaagaacaa atgaggcgcc 240

aaagagagga aagttacagc cgaatgggct acatggatcc acgggaaaga gacatgcgaa 300

tgggtggcgg aggagcaatg aacatgggag atccctatgg ttcaggaggc cagaaatttc 360

cacctctagg aggtggtggt ggcataggtt atgaagctaa tcctggcgtt ccaccagcaa 420

ccatgagtgg ttccatgatg ggaagtgaca tgcgtactga gcgctttggg cagggaggtg 480

cggggcctgt gggtggacag ggtcctagag gaatggggcc tggaactcca gcaggatatg 540

gtagagggag agaagagtac gaaggc 566

152

518

Homo sapien

152

ttcgtgaaga ccctgactgg taagaccatc actctcgaag tggagcccga gtgacaccat 60

tgagaatgtc aaggcaaaga tccaagacaa ggaaggcatc cctcctgacc agcakaggtt 120

gatctttgct gggaaacagc tggaagatgg acgcaccctg tctgactaca acatccagaa 180

agagtccacc ctgcacctgg tgctccgtct cagaggtggg atgcaaatct tcgtgaagac 240

cctgactggt aagaccatca ccctcgaggt ggagcccagt gacaccatcg agaatgtcaa 300

ggcaaagatc caagataagg aaggcatccc tcctgatcag cagaggttga tctttgctgg 360

gaaacagctg gaagatggac gcaccctgtc tgactacaac atccagaaag agtccactct 420

gcacttggtc ctgcgcttga gggggggtgt ctaagtttcc ccttttaagg tttcaacaaa 480

tttcattgca ctttcctttc aataaagttg ttgcattc 518

153

542

Homo sapien

153

gcgcgggtgc gtgggccact gggtgaccga cttagcctgg ccagactctc agcacctgga 60

agcgccccga gagtgacagc gtgaggctgg gagggaggac ttggcttgag cttgttaaac 120

tctgctctga gcctccttgt cgcctgcatt tagatggctc ccgcaaagaa gggtggcgag 180

aagaaaaagg gccgttctgc catcaacgaa gtggtaaccc gagaatacac catcaacatt 240

cacaagcgca tccatggagt gggcttcaag aagcgtgcac ctcgggcact caaagagatt 300

cggaaatttg ccatgaagga gatgggaact ccagatgtgc gcattgacac caggctcaac 360

aaagctgtct gggccaaagg aataaggaat gtgccatacc gaatccgtgt gcggctgtcc 420

agaaaacgta atgaggatga agattcacca aataagctat atactttggt tacctatgta 480

cctgttacca ctttcaaaaa tctacagaca gtcaatgtgg atgagaacta atcgctgatc 540

gt 542

154

411

Homo sapien

154

aattctttat ttaaatcaac aaactcatct tcctcaagcc ccagaccatg gtaggcagcc 60

ctccctctcc atcccctcac cccacccctt agccacagtg aagggaatgg aaaatgagaa 120

gccacgaggg cccctgccag ggaaggctgc cccagatgtg tggtgagcac agtcagtgca 180

gctgtggctg gggcagcagc tgccacaggc tcctccctat aaattaagtt cctgcagcca 240

cagctgtggg agaagcatac ttgtagaagc aaggccagtc cagcatcaga aggcagaggc 300

agcatcagtg actcccagcc atggaatgaa cggaggacac agagctcaga gacagaacag 360

gccaggggga agaaggagag acagaatagg ccagggcatg gcggtgaggg a 411

155

tgatgaatct gggtgggctg gcagtagccc gagatgatgg gctcttctct ggggatccca 60

actggttccc taagaaatcc aaggagaatc ctcggaactt ctcggataac cagctgcaag 120

agggcaagaa cgtgatcggg ttacagatgg gcaccaaccg cggggcgtct cangcaggca 180

tgactggcta cgggatgcca cgccagatcc tctgatccca ccccaggcct tgcccctgcc 240

ctcccacgaa tggttaatat atatgtagat atatatttta gcagtgacat tcccagagag 300

ccccagagct ctcaagctcc tttctgtcag ggtggggggt tcaagcctgt cctgtcacct 360

ctgaagtgcc tgctggcatc ctctccccca tgcttactaa tacattccct tccccatagc 420

c 421

156

670

Homo sapien

156

agcggagctc cctcccctgg tggctacaac ccacacacgc caggctcagg catcgagcag 60

aactccagcg actgggtaac cactgacatt caggtgaagg tgcgggacac ctacctggat 120

acacaggtgg tgggacagac aggtgtcatc cgcagtgtca cggggggcat gtgctctgtg 180

tacctgaagg acagtgagaa ggttgtcagc atttccagtg agcacctgga gcctatcacc 240

cccaccaaga acaacaaggt gaaagtgatc ctgggcgagg atcgggaagc cacgggcgtc 300

ctactgagca ttgatggtga ggatggcatt gtccgtatgg accttgatga gcagctcaag 360

atcctcaacc tccgcttcct ggggaagctc ctggaagcct gaagcaggca gggccggtgg 420

acttcgtcgg atgaagagtg atcctccttc cttccctggc ccttggctgt gacacaagat 480

cctcctgcag ggctaggcgg attgttctgg atttcctttt gtttttcctt ttaggtttcc 540

atcttttccc tccctggtgc tcattggaat ctgagtagag tctgggggag ggtccccacc 600

ttcctgtacc tcctccccac agcttgcttt tgttgtaccg tctttcaata aaaagaagct 660

gtttggtcta 670

157

421

Homo sapien

157

ggttcacagc actgctgctt gtgtgttgcc ggccaggaat tccaggctca caaggctatc 60

ttagcagctc gttctccggt ttttagtgcc atgtttgaac atgaaatgga ggagagcaaa 120

aagaatcgag ttgaaatcaa tgatgtggag cctgaagttt ttaaggaaat gatgtgcttc 180

atttacacgg ggaaggctcc aaacctcgac aaaatggctg atgatttgct ggcagctgct 240

gacaagtatg ccctggagcg cttaaaggtc atgtgtgagg atgccctctg cagtaacctg 300

tccgtggaga acgctgcaga aattctcatc ctggccgacc tccacagtgc agatcagttg 360

aaaactcagg cagtggattt catcaactat catgcttcgg atgtcttgga gacctcttgg 420

g 421

158

321

Homo sapien

158

tcgtagccat ttttctgctt ctttggagaa tgacgccaca ctgactgctc attgtcgttg 60

gttccatgcc aattggtgaa atagaacctc atccggtagt ggagccggag ggacatcttg 120

tcatcaacgg tgatggtgcg atttggagca taccagagct tggtgttctc gccatacagg 180

gcaaagaggt tgtgacaaag aggagagata cggcatgcct gtgcagccct gatgcacagt 240

tcctctgctg tgtactctcc actgcccagc cggaggggct ccctgtccga cagatagaag 300

atcacttcca cccctggctt g 321

159

596

Homo sapien

159

tggcacactg ctcttaagaa actatgawga tctgagattt ttttgtgtat gtttttgact 60

cttttgagtg gtaatcatat gtgtctttat agatgtacat acctccttgc acaaatggag 120

gggaattcat tttcatcact gggagtgtcc ttagtgtata aaaaccatgc tggtatatgg 180

cttcaagttg taaaaatgaa agtgacttta aaagaaaata ggggatggtc caggatctcc 240

actgataaga ctgtttttaa gtaacttaag gacctttggg tctacaagta tatgtgaaaa 300

aaatgagact tactgggtga ggaaattcat tgtttaaaga tggtcgtgtg tgtgtgtgtg 360

tgtgtgtgtg ttgtgttgtg ttttgttttt taagggaggg aatttattat ttaccgttgc 420

ttgaaattac tgkgtaaata tatgtytgat aatgatttgc tytttgvcma ctaaaattag 480

gvctgtataa gtwctaratg cmtccctggg kgttgatytt ccmagatatt gatgatamcc 540

cttaaaattg taaccygcct ttttcccttt gctytcmatt aaagtctatt cmaaag 596

160

515

Homo sapien

160

gggggtaggc tctttattag acggttattg ctgtactaca gggtcagagt gcagtgtaag 60

cagtgtcaga ggcccgcgtt cagcccaaga atgtggattt tctctcccta ttgatcacag 120

tgggtgggtt tcttcagaaa agccccagag gcagggacca gtgagctcca aggttagaag 180

tggaactgga aggcttcagt cacatgctgc ttccacgctt ccaggctggg cagcaaggag 240

gagatgccca tgacgtgcca ggtctcccca tctgacacca gtgaagtctg gtaggacagc 300

agccgcacgc ctgcctctgc caggaggcca atcatggtag gcagcattgc agggtcagag 360

gtctgagtcc ggaataggag caggggcagg tccctgcgga gaggcacttc tggcctgaag 420

acagctccat tgagcccctg cagtacaggy gtagtgcctt ggaccaagcc cacagcctgg 480

taaggggcgc ctgccagggc cacggccagg aggca 515

161

936

Homo sapien

161

taatttctta gtcgtttgga atccttaagc atgcaaaagc tttgaacaga agggttcaca 60

aaggaaccag ggttgtctta tggcatccag ttaagccaga gctgggaatg cctctgggtc 120

atccacatca ggagcagaag cacttgactt gtcggtcctg ctgccacggt ttgggcgccc 180

accacgccca cgtccacctc gtcctcccct gccgccacgt cctgggcggc caaggtctcc 240

aaaattgatc tccagctgag acgttatatc atttgctggc ttccggaaat gatggtccat 300

aaccgaatct tcagcatgag cctcttcact ctttgattta tgaagaacaa atcccttctt 360

ccactgccca tcagcacctt catttggttt tcggatatta aattctactt ttgcccggtc 420

cttattttga atagccttcc actcatccaa agtcatctct tttggaccct cctcttttac 480

ctcttcaact tcattctcct tattttcagt gtctgccact ggatgatgtt cttcaccttc 540

aggtgtttcc tcagtcacat ttgattgatc caagtcagtt aattcgtctt tgacagttcc 600

ccagttgtga gatccgctac ctccacgttt gtcctcgtgc ttcaggccag atctatcact 660

tccactatgc ctatcaaatt cacgtttgcc acgagaatca aatccatctc ctcggcccat 720

tccacgtcca cggccccctc gacctcttcc aagaccacca cgacctcgaa taggtcggtc 780

aataatcggt ctatcaactg aaaattcgcc tccttcaccc ttttcttcaa gtggcttttc 840

gaatcttcgt tcacgaggtg gtcgcctttc tggtcttcta tcaattattt tcccttcacc 900

ctgaagttgt tgatcaggtc ttcttccaac tcgtgc 936

162

950

Homo sapien

162

aagcggatgg acctgagtca gccgaatcct agccccttcc cttgggcctg ctgtggtgct 60

cgacatcagt gacagacgga agcagcagac catcaaggct acgggaggcc cggggcgctt 120

gcgaagatga agtttggctg cctctccttc cggcagcctt atgctggctt tgtcttaaat 180

ggaatcaaga ctgtggagac gcgctggcgt cctctgctga gcagccagcg gaactgtacc 240

atcgccgtcc acattgctca cagggactgg gaaggcgatg cctgtcggga gctgctggtg 300

gagagactcg ggatgactcc tgctcagatt caggccttgc tcaggaaagg ggaaaagttt 360

ggtcgaggag tgatagcggg actcgttgac attggggaaa ctttgcaatg ccccgaagac 420

ttaactcccg atgaggttgt ggaactagaa aatcaagctg cactgaccaa cctgaagcag 480

aagtacctga ctgtgatttc aaaccccagg tggttactgg agcccatacc taggaaagga 540

ggcaaggatg tattccaggt agacatccca gagcacctga tccctttggg gcatgaagtg 600

tgacaagtgt gggctcctga aaggaatgtt ccrgagaaac cagctaaatc atggcacctt 660

caatttgcca tcgtgacgca gacctgtata aattaggtta aagatgaatt tccactgctt 720

tggagagtcc cacccactaa gcactgtgca tgtaaacagg ttcctttgct cagatgaagg 780

aagtaggggg tggggctttc cttgtgtgat gcctccttag gcacacaggc aatgtctcaa 840

gtactttgac cttagggtag aaggcaaagc tgccagtaaa tgtctcagca ttgctgctaa 900

ttttggtcct gctagtttct ggattgtaca aataaatgtg ttgtagatga 950

163

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt 180

acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg 240

ggagggcttt gttggagacc ttgcacttgt actccttgcc attcaaccag tcctggtgca 300

ngacggtgag gacgctnacc acacggtacg ngctggtgta ctgctcctcc cgcggctttg 360

tcttggcatt atgcacctcc acgccgtcca cgtaccaatt gaacttgacc tcagggtctt 420

cgtggctcac gtccaccacc acgcatgtaa cctcaaanct cggncgcgan cacgc 475

164

476

Homo sapien

164

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 180

ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc 240

ccccatcgag aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac 300

cctgccccca tcccgggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa 360

aggcttctat cccagcgaca tcgcccgtgg agtgggagag caatgggcag ccggagaaca 420

actacaagac cacgcctccc gtgctggact ccgacacctg ccgggcggcc gctcga 476

165

agcgtggttn cggccgaggt cccaaccaag gctgcancct ggatgccatc aaagtcttct 60

gcaacatgga gactggtgag acctgcgtgt accccactca gcccagtgtg gcccagaaga 120

actggtacat cagcaagaac cccaaggaca agaggcatgt ctggttcggc gagagcatga 180

ccgatggatt ccagttcgag tatggcggcc agggctccga ccctgccgat gtggacctgc 240

ccgggcggnc gctcga 256

166

332

Homo sapien

166

agcgtggtcg cggccgaggt caagaacccc gcccgcacct gccgtgacct caagatgtgc 60

cactctgact ggaagagtgg agagtactgg attgacccca accaaggctg caacctggat 120

gccatcaaag tcttctgcaa catggagact ggtgagacct gcgtgtaccc cactcagccc 180

agtgtggccc agaagaactg gtacatcagc aagaacccca aggacaagag gcatgtctgg 240

ttcggcgaga gcatgaccga tggattccag ttcgagtatg gcggccaggg ctccgaccct 300

gccgatgtgg acctgcccgg gcggccgctc ga 332

167

tcgagcggtc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggncat gctctcgccg aaccagacat gcctcttgnc cttggggttc 120

ttgctgatgt accagntctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccantctcca tgttgcanaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagacagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggt cgcgaccacg ct 332

168

tcgagcggcc gcccgggcag gtcctcctca gagcggtagc tgttcttatt gccccggcag 60

cctccataga tnaagttatt gcangagttc ctctccacgt caaagtacca gcgtgggaag 120

gatgcacggc aaggcccagt gactgcgttg gcggtgcagt attcttcata gttgaacata 180

tcgctggagt ggacttcaga atcctgcctt ctgggagcac ttgggacaga ggaatccgct 240

gcattcctgc tggtggacct cggccgcgac cacgct 276

169

276

Homo sapien

169

agcgtggtcg cggccgaggt ccaccagcag gaatgcagcg gattcctctg tcccaagtgc 60

tcccagaagg caggattctg aagaccactc cagcgatatg ttcaactatg aagaatactg 120

caccgccaac gcagtcactg ggccttgccg tgcatccttc ccacgctggt actttgacgt 180

ggagaggaac tcctgcaata acttcatcta tggaggctgc cggggcaata agaacagcta 240

ccgctctgag gaggacctgc ccgggcggcc gctcga 276

170

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagccagaa tggcacatct tgaggtcacg gcangtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

171

333

Homo sapien

171

agcgtggtcg cggccgaggt caagaaaccc cgcccgcacc tgccgtgacc tcaagatgtg 60

ccactctggc tggaagagtg gagagtactg gattgacccc aaccaaggct gcaacctgga 120

tgccatcaaa gtcttctgca acatggagac tggtgagacc tgcgtgtacc ccactcagcc 180

cagtgtggcc cagaagaact ggtacatcag caagaacccc aaggacaaga ggcatgtctg 240

gctcggcgag agcatgaccg atggattcca gttcgagtat ggcggccagg gctccgaccc 300

tgccgatgtg gacctgcccg ggcggccgct cga 333

172

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagntcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctgnaatgg ggcccatgan atggttgnct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgn gggcggtgng gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca naagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctgntc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgctgtct ttttccttcc aatcangggc tcgctcttct gaatattctt 480

cagggcaatg acataaattg tatattcggt tcccggttcc aggccag 527

173

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgangaacat ggntttaggc ggaccacacc ggccacaacg 480

ggcaccccca taaggcatag gccaagaaca tacccgncga atgtaggaca agaagctctn 540

tctcanacaa ncatctcatg ggccccattc cangacactt ctgagtacat canttcatgg 600

catcctggtg gcactgataa aaacccttac agtta 635

174

agcgtggtcg cgggcgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcanggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg ntcccgggtn cagccaataa taataaccct 540

ctgtgacacc anggcggggc cgaagganca ct 572

175

agcgtggtcg cggccgaggt cctcaccaga ggtaccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttangct ttggaagtgg tcatttcaga tgtgattcat ctagatggtg ccatgacaat 300

ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg acctgcccgg 360

gcggccgctc ga 372

176

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ntgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggta cctctggtga ggacctcggc 360

cgcgaccacg ct 372

177

agcgtggccg cggccgaggt ccattggctg gaacggcatc aacttggaag ccagtgatcg 60

tctcagcctt ggttctccag ctaatggtga tggnggtctc agtagcatct gtcacacgag 120

cccttcttgg tgggctgaca ttctccagag tggtgacaac accctgagct ggtctgcttg 180

tcaaagtgtc cttaagagca tagacactca cttcatattt ggcgnccacc ataagtcctg 240

atacaaccac ggaatgacct gtcaggaac 269

178

529

Homo sapien

178

tcgagcggcc gcccgggcag gtcctcagac cgggttctga gtacacagtc agtgtggttg 60

ccttgcacga tgatatggag agccagcccc tgattggaac ccagtccaca gctattcctg 120

caccaactga cctgaagttc actcaggtca cacccacaag cctgagcgcc cagtggacac 180

cacccaatgt tcagctcact ggatatcgag tgcgggtgac ccccaaggag aagaccggac 240

caatgaaaga aatcaacctt gctcctgaca gctcatccgt ggttgtatca ggacttatgg 300

cggccaccaa atatgaagtg agtgtctatg ctcttaagga cactttgaca agcagaccag 360

ctcagggtgt tgtcaccact ctggagaatg tcagcccacc aagaagggct cgtgtgacag 420

atgctactga gaccaccatc accattagct ggagaaccaa gactgagacg atcactggct 480

tccaagttga tgccgttcca gccaatggac ctcggccgcg accacgctt 529

179

agcgtggtcg cggccgaggt ctggccgaac tgccagtgta cagggaagat gtacatgtta 60

tagntcttct cgaagtcccg ggccagcagc tccacggggt ggtctcctgc ctccaggcgc 120

ttctcattct catggatctt cttcacccgc agcttctgct tctcagtcag aaggttgttg 180

tcctcatccc tctcatacag ggtgaccagg acgttcttga gccagtcccg catgcgcagg 240

gggaattcgg tcagctcaga gtccaggcaa ggggggatgt atttgcaagg cccgatgtag 300

tccaagtgga gcttgtggcc cttcttggtg ccctccaagg tgcactttgt ggcaaagaag 360

tggcaggaag agtcgaaggt cttgttgtca ttgctgcaca ccttctcaaa ctcgccaatg 420

ggggctgggc agacctgccc gggcggccgc tcga 454

180

tcgagcggcc gcccgggcag gtctgcccag cccccattgg cgagtttgag aaggngtgca 60

gcaatgacaa caagaccttc gactcttcct gccacttctt tgccacaaag tgcaccctgg 120

agggcaccaa gaagggccac aagctccacc tggactacat cgggccttgc aaatacatcc 180

ccccttgcct ggactctgag ctgaccgaat tccccctgcg catgcgggac tggctcaaga 240

acgtcctggt caccctgtat gagagggatg aggacaacaa ccttctgact gagaagcana 300

agctgcgggt gaagaanatc catgagaatg anaagcgcct gnaggcanga gaccaccccg 360

tggagctgct ggcccgggac ttcgagaaga actataacat gtacatcttc cctgtacact 420

ggcagttcgg ccagacctcg gccgcgacca cgct 454

181

agcgtggntg cggacgacgc ccacaaagcc attgtatgta gttttanttc agctgcaaan 60

aataccncca gcatccacct tactaaccag catatgcaga ca 102

182

tcgagcggtc gcccgggcag gtctgggcgg atagcaccgg gcatattttg gaatggatga 60

ggtctggcac cctgagcagc ccagcgagga cttggtctta gttgagcaat ttggctagga 120

ggatagtatg cagcacggtt ctgagtctgt gggatagctg ccatgaagna acctgaagga 180

ggcgctggct ggtangggtt gattacaggg ctgggaacag ctcgtacact tgccattctc 240

tgcatatact ggntagtgag gcgagcctgg cgctcttctt tgcgctgagc taaagctaca 300

tacaatggct ttgnggacct cggccgcgac cacgctt 337

183

374

Homo sapien

183

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat gacaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagaag ttgcccacgg taacaacctc ttcccgaacc ttatgcctct 300

gctggtcttt caagtgcctc cactatgatg ttgtaggtgg cacctctggt gaggacctcg 360

gccgcgacca cgct 374

184

agcgtggttt gcggccgagg tcctcaccan aggtgccacc tacaacatca tagtggaggc 60

actgaaagac cagcagaggc ataaggttcg ggaagaggtt gttaccgtgg gcaactctgt 120

caacgaaggc ttgaaccaac ctacggatga ctcgtgcttt gacccctaca cagnttccca 180

ttatgccgtt ggagatgagt gggaacgaat gtctgaatca ggctttaaac tgttgtgcca 240

gtgcttangc tttggaagtg gtcatttcag atgtgattca tctanatggt gtcatgacaa 300

tggtgngaac tacaagattg gagagaagtg gnaccgtcag ggganaaaat ggacctgccc 360

gggcggcncg ctcga 375

185

agcgtggtcg cggccgaggt ctggcttnct gctcangtga ttatcctgaa ccatccaggc 60

caaataagcg ccggctatgc ccctgnattg gattgccaca cggctcacat tgcatgcaag 120

tttgctgagc tgaaggaaaa gattgatc 148

186

tcgagcggcc gcccgggcag gtccaattga aacaaacagt tctgagaccg ttcttccacc 60

actgattaag agtggggngg cgggtattag ggataatatt catttagcct tctgagcttt 120

ctgggcagac ttggtgacct tgccagctcc agcagccttc tggtccactg ctttgatgac 180

acccaccgca actgtctgtc tcatatcacg aacagcaaag cgacccaaag gtggatagtc 240

tgagaagctc tcaacacaca tgggcttgcc aggaaccata tcaacaatgg gcagcatcac 300

cagacttcaa gaatttaagg gccatcttcc agctttttac cagaacggcg atcaatcttt 360

tccttcagct cagcaaactt gcatgcaatg tgagccg 397

187

tcgagcggcc gcccgggcag gtccagaggg ctgtgctgaa gtttgctgct gccactggag 60

ccactccaat tgctggccgc ttcactcctg gaaccttcac taaccagatc caggcagcct 120

tccgggagcc acggcttctt gtggntactg accccagggc tgaccaccag cctctcacgg 180

aggcatctta tgttaaccta cctaccattg cgctgtgtaa cacagattct cctctgcgct 240

atgtggacat tgccatccca tgcaacaaca agggagctca ctcagngggg tttgatgtgg 300

tggatgctgg ctcgggaagt tctgcgcatg cgtggcacca tttcccgtga acacccatgg 360

gangncatgc ctgatctgga cttctacaga gatcctgaag agattgaaaa agaagaacag 420

gctgnttgct ganaaagcaa gtgaccaagg angaaatttc angggtgaaa nggactgctc 480

ccgctcctga attcactgct actcaacctg angntgcaga ctggtcttga aggngnacan 540

gggccctctg ggcctattta agcancttcg gtcgcgaaca cgnt 584

188

agcgtgngtc gcggccgagg tgctgaatag gcacagaggg cacctgtaca ccttcagacc 60

agtctgcaac ctcaggctga gtagcagtga actcaggagc gggagcagtc cattcaccct 120

gaaattcctc cttggncact gccttctcag cagcagcctg ctcttctttt tcaatctctt 180

caggatctct gtagaagtac agatcaggca tgacctccca tgggtgttca cgggaaatgg 240

tgccacgcat gcgcagaact tcccgagcca gcatccacca catcaaaccc actgagtgag 300

ctcccttgtt gttgcatggg atgggcaatg tccacatagc gcagaggaga atctgtgtta 360

cacagcgcaa tggtaggtag gttaacataa gatgcctccg cgagaagctg gtggtcagcc 420

ctggggtcaa gtaaccacaa gaagccgtgg ctcccggaag gctgcctgga tctggttagt 480

gaaggntcca ggagtgaagc ggccaacaat tggagtggct tcagtggcaa gcagcaaact 540

tcagcacaag ccctctggac ctgcccggcg gccgctcga 579

189

tcgagcggcc gcccgggcag gtccattttc tccctgacgg ncccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctcn tccccgaacc ttatgcctct 300

gctgggcttt cagngcctcc actatgatgn tgtagggggg cacctctggn gangacctcg 360

gccgcgacca cgct 374

190

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggctcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttangct ttggaagtgg gtcatttcag atgtgattca tctagatggt gccatgacaa 300

tggngngaac tacaagattg gagagaagtg gnaccgncag ggagaaaatg gacctgcccg 360

ggcggccgct cga 373

191

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggntg caaccttggt tggggtcaat 240

ccagtactct ccactcttcc agccagagtg gcacatcttg aggtcacggc aggtgcggnc 300

gggggntttt gcggctgccc tctggncttc ggntgtnctc natctgctgg ctca 354

192

tcgagcggcc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggcccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc 240

cagcagatcg agaacatccg gagcccagag ggcagncgca agaaccccgc ccgcacctgc 300

cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac 360

caagctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt gagacctgcg 420

tgtaccccac tcagcccagt gtggcccaaa agaactggta catcagcaag aaccccaagg 480

acaagaagca tgtctggttc ggcgagaaca tgaccgatgg attccagttc gagtatggcg 540

ggcagggctc cgaccctgcc gatggggacc ttggccgcga acacgct 587

193

agcgtggnng cggccgaggt ataaatatcc agnccatatc ctccctccac acgctganag 60

atgaagctgt ncaaagatct cagggtggan aaaaccat 98

194

240

Homo sapien

194

tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca 60

gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat 120

ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat 180

ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct 240

195

cgagcgggcg accgggcagg tncagactcc aatccanana accatcaagc cagatgtcag 60

aagctacacc atcacaggtt tacaaccagg cactgactac aaganctacc tgcacacctt 120

gaatgacaat gctcggagct cccctgtggt catcgacgcc tccactgcca ttgatgcacc 180

atccaacctg cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc 240

acgtgccagg attaccggta catcatcnag tatganaagc ctgggcctcc tcccagagaa 300

gnggtccctc ggccccgccc tgntgtccca naggntacta ttactgngcc ngcaaccggc 360

aaccgatatc nattttgnca ttggccttca acaataatta 400

196

agcgtggttc gcggccgang tcctgtcaga gtggcactgg tagaagttcc aggaaccctg 60

aactgtaagg gttcttcatc agngccaaca ggatgacatg aaatgatgta ctcagaagtg 120

tcctggaatg gggcccatga gatggttgtc tgagagagag cttcttgncc tgtctttttc 180

cttccaatca ggggctcgct cttctgatta ttcttcaggg caatgacata aattgtatat 240

tcgggtcccg gntccaggcc agtaatagta ncctctgtga caccagggcg gngccgaggg 300

accacttctc tgggaggaga cccaggcttc tcatacttga tgatgtaacc ggtaatcctg 360

gcacgtggcg gctgccatga taccagcaag gaattggggt gtggtggcca ggaaacgcag 420

gttggatggn gcatcaatgg cagtggaggc cgtcgatgac cacaggggga gctccgacat 480

tgtcattcaa ggtg 494

197

agcgtggncg cggccgaggt gcagcgcggg ctgtgccacc ttctgctctc tgcccaacga 60

taaggagggt ncctgccccc aggagaacat taactntccc cagctcggcc tctgccgg 118

198

tcgagcggcc gcccgggcag gttttttttg ctgaaagtgg ntactttatt ggntgggaaa 60

gggagaagct gtggtcagcc caagagggaa tacagagncc cgaaaaaggg gagggcaggt 120

gggctggaac cagacgcagg gccaggcaga aactttctct cctcactgct cagcctggtg 180

gtggctggag ctcanaaatt gggagtgaca caggacacct tcccacagcc attgcggcgg 240

catttcatct ggccaggaca ctggctgtcc acctggcact ggtcccgaca gaagcccgag 300

ctggggaaag ttaatgttca cctgggggca ggaaccctcc ttatcattgn gcagagagca 360

gaaggtggca cagcccgcgc tgcacctcgg ccgcgaccac gct 403

199

tcgagcggcc gcccgggcag gtccaccata agtcctgata caaccacgga tgagctgtca 60

ggagcaaggt tgatttcttt cattggtccg gncttctcct tgggggncac ccgcactcga 120

tatccagtga gctgaacatt gggtggcgtc cactgggcgc tcaggct 167

200

tcgagcggtt cgcccgggca ggtccaccac acccaattcc ttgctggtat catggcagcc 60

gccacgtgcc aggattaccg gctacatcat caagtatgag aagcctgggt ctcctcccag 120

agaagcggtc cctcggcccc gccctggtgt cacagaggct actattactg gcctggaacc 180

gggaaccgaa tatacaattt atgtcattgn cctgaagaat aatcannaan agcgancccc 240

tgattggaag ga 252

201

91

Homo sapien

201

agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt t 91

202

tcgagcggnc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca 60

gtccgtgtgc ggggaggtaa caagaaatac cgtgccctga ggttggacgt ggggaatttc 120

tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca 180

tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatcgac 240

agcacaccgt accgacagtg gtacgagtcc cactatgcgc tgcccctggg ccgcaagaag 300

ggagccaagc tgactcctga ggaagaagag attttaaaca aaaaacgatc taanaaaaaa 360

aaaacaat 368

203

340

Homo sapien

203

agcgtggtcg cggccgaggt gaaatggtat tcagcttcct ggcacttctg gtcagcaacc 60

cagtgttggg caacaaatga tctttgagga acatggtttt aggcggacca caccgcccac 120

aacggccacc cccataaggc ataggccaag accatacccg ccgaatgtag gacaagaagc 180

tctctctcag acaaccatct catgggcccc attccaggac acttctgagt acatcatttc 240

atgtcatcct gttggcactg atgaagaacc cttacagttc agggttcctg gaacttctac 300

cagtgccact ctgacaggac ctgcccgggc ggccgctcga 340

204

341

Homo sapien

204

tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct 60

gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt 120

gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg 180

cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct 240

aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc 300

aggaagctga ataccatttc acctcggccg cgaccacgct a 341

205

tcgagcggcc gcccgggcag gtctcccttc ttgcggccca ggggcagcgc atagtgggac 60

tcgtaccact gtcggtacgg tgtgctgtcg atgagcacga tgcaattctt caccagggtc 120

ttggtacgaa ccagctcgtt attagatgca ttgtagacaa catcgatgat ccttgtttta 180

cgagtacaac actctgagcc ccaggagaaa ttccccacgt ccaacctcag ggcacggtat 240

ttcttgttac ctccccgcac acggactgtg tggatgcggc gggggccaag ctgactcctg 300

aggaagaaga gattttaaac aaaaaacgat ctaaaaaaat tcagaagaaa tatgatgaaa 360

ggaaaaagaa tgccaaaatc agcagtctcc tggaggagca gttccagcag ggcaagcttc 420

ttgcgtgcat cgcttcaagg ccgggacagt gtgaccgagc agatggctat gtgctagagg 480

gcaaagaagt ggagttctat cttaagaaaa tcagggccca gaatggtgng tcttcaacta 540

atccaaaggg gagtttcaga ccagtgcaat cagcaaaaac attgatactg ntggccaaat 600

ttattggtgc agggcttgca cantangann ggctgggtct tggggcttgg attggnacaa 660

gctttggcag ccttttcttt ggttttgcca aaaacctttt gntgaagang anacctnggg 720

cggacccctt aaccgattcc acnccnggng gcgttctang gncccncttg 770

206

agcgtggtcg cggccgaggt ctgctgcttc agcgaagggt ttctggcata accaatgata 60

aggctgccaa agactgttcc aataccagca ccagaaccag ccactcctac tgttgcagca 120

cctgcaccaa taaatttggc agcagtatca atgtctctgc tgattgcact ggtctgaaac 180

tccctttgga ttagctgaga cacaccattc tgggccctga ttttcctaag atagaactcc 240

aactctttgc cctctagcac atagccatct gctcggtcac actgtcccgg ccttgaagcg 300

atgcacgcaa gaagcttgcc ctgctggaac tgctcctcca ggagactgct gattttggca 360

ttctttttcc tttcatcata tttcttctga atttttttag atcgtttttt gtttaaaatc 420

tcttcttcct caggagtcag cttggccccc gccgcatcca cacagtccgt gtgcggggag 480

gtaacaagaa ataccgtgcc ctgaggttgg acgtggggaa tttctcctgg ggctcagagt 540

ggtgtactcg taaaacaagg atcatcgatg gtgnctacaa tgcatctaat aacgagctgg 600

gtcggaccca aagaacctgg ngaanaaatg gatcgnctca tcgacaggac accgtacccg 660

acaggggnac gantcccact atgcgcttgc ccctgggccg caanaaagga aaactgcccg 720

ggcggccntc gaaagcccaa ttntggaaaa aatccatcac actgggnggc cngtcgagca 780

tgcatntana ggggcccatt ccccctnann 810

207

257

Homo sapien

207

tcgagcggcc gcccgggcag gtccccaacc aaggctgcaa cctggatgcc atcaaagtct 60

tctgcaacat ggagactggt gagacctgcg tgtaccccac tcagcccagt gtggcccaga 120

agaactggta catcagcaag aaccccaagg acaagaggca tgtctggttc ggcgagagca 180

tgaccgatgg attccagttc gagtatggcg gccagggctc cgaccctgcc gatgtggacc 240

tcggccgcga ccacgct 257

208

257

Homo sapien

208

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggacctg 240

cccgggcggc cgctcga 257

209

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgaggaacat ggntttaggc ggaccacacc gcccacaacg 480

gccaccccca taaggcatag gccaagacca tacccgccga atgtaggaca agaagctntn 540

tntcanacac catntnatgg gccccattcc aggacacttc tgagtacatc atttatgnca 600

tctgtggcac ttgatgaaaa cccttacagt tcagggttct ggaactttta ccaggcctnt 660

tacaggactn ggccggacnc cttaagccna ttncaccctg gggcgttcta nggtcccact 720

cgnncactgg ngaaaatggc tactgtn 747

210

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgngaaac tccnaggaca 180

ngagggctaa attccatgaa gtttgtggat ggcctgatga tccacaatcg gagaccctgt 240

taactactac cgtctnaccn cctgctgtnc ncccccnttt ctgctnaana catngggntn 300

ntncttgncc ntccttgggt ngaanatnna atngcctncc cnttcntanc nctactngnt 360

ccananttgg cctttaaana atccnccttg ccttnnncac tgttcanntn tttnntcgta 420

aaccctatna nttnnattan atnntnnnnn nctcaccccc ctcntcattn anccnatang 480

ctnnnaantc cttnanncct cccncccnnt ncnctcntac tnantncttc tnncccatta 540

cnnagctctt tcntttaana taatgnngcc nngctctnca tntctacnat ntgnnnaatn 600

cccccncccc cnancgnntt tttgacctnn naacctcctt tcctcttccc tncnnaaatt 660

ncnnanttcc ncnttccnnc ntttcggntn ntcccatnct ttccannnct tcantctanc 720

ncnctncaac ttattttcct ntcatccctt nttctttaca nnccccctnn tctactcnnc 780

nnttncatta natttgaaac tnccacnnct anttncctcn ctctacnntt ttattttncg 840

ntcnctctac ntaatanttt aatnanttnt cn 872

211

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacaa gcagtgtcaa cgtagtaagt taacagggtc tccgctgtgg 300

atcatcaggc catccacaaa cttcatggat ttagccctct gtcctcggag tttcccagac 360

accacaacct cgcagccttt ggccccactc tccatgatga accgcagcac accatagcag 420

gccctccgca caagcaagcc ctcctaagaa tttgtaacgc ananactctg ctggcaatgg 480

cacacaaacc tctagtggac ctcggncgcg accacgc 517

212

tcgagcggcc gcccgggcag gtctggtcca ggatagcctg cgagtcctcc tactgctact 60

ccagacttga catcatatga atcatactgg ggagaatagt tctgaggacc agtagggcat 120

gattcacaga ttccaggggg gccaggagaa ccaggggacc ctggttgtcc tggaatacca 180

gggtcaccat ttctcccagg aataccagga gggcctggat ctcccttggg gccttgaggt 240

ccttgaccat taggagggcg agtaggagca gttggaggct gtgggcaaac tgcacaacat 300

tctccaaatg gaatttctgg gttggggcag tctaattctt gatccgtcac atattatgtc 360

atcgcagaga acggatcctg agtcacagac acatatttgg catggttctg gcttccagac 420

atctctatcc gncataggac tgaccaagat gggaacatcc tccttcaaca agcttnctgt 480

tgtgccaaaa ataatagtgg gatgaagcag accgagaagt anccagctcc cctttttgca 540

caaagcntca tcatgtctaa atatcagaca tgagacttct ttgggcaaaa aaggagaaaa 600

agaaaaagca gttcaaagta nccnccatca agttggttcc ttgcccnttc agcacccggg 660

ccccgttata aaacacctng ggccggaccc ccctt 695

213

agcgtggtcg cggccgaggt gttttatgac gggcccggtg ctgaagggca gggaacaact 60

tgatggtgct actttgaact gcttttcttt tctccttttt gcacaaagag tctcatgtct 120

gatatttaga catgatgagc tttgtgcaaa aggggagctg gctacttctc gctctgcttc 180

atcccactat tattttggca caacaggaag ctgttgaagg aggatgttcc catcttggtc 240

agtcctatgc ggatagagat gtctggaagc cagaaccatg ccaaatatgt gtctgtgact 300

caggatccgt tctctgcgat gacataatat gtgacgatca agaattagac tgccccaacc 360

cagaaattcc atttggagaa tgttgtgcag tttgcccaca gcctccaact gctcctactc 420

gccctcctaa tggtcaagga cctcaaggcc ccaagggaga tccaggccct cctggtattc 480

ctgggagaaa tggtgaccct ggtattccag gacaaccagg gtcccctggt tctcctggcc 540

cccctggaat cnggngaatc atgccctact ggtcctcaaa ctattctccc anatgattca 600

tatgatgtca agtctgggat agcnagtang ganggactcg caggctattc tggaccanac 660

ctgccggggg ggcgttcgaa agcccgaatc tgcananntn cnttcacact ggcggccgtc 720

gagctgcttt aaaagggcca ttccnccttt agngnggggg antacaatta ctnggcggcg 780

ttttanancg cgngnctggg aaat 804

214

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc 300

ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaggctctt 360

gagggtggtg tccacctcga ggtcacggtc acgaaccaca ttggcatcat cagcccggta 420

gtagcggcca ccatcgtgag ccttctcttg angtggctgg ggcaggaact gaagtcgaaa 480

ccagcgctgg gaggaccagg gggaccaana ggtccaggaa gggcccgggg gggaccaaca 540

ggaccagcat caccaagtgc gacccgcgag aacctgcccg gccgnccgct cgaa 594

215

tcgagcgnnc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggtccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc 240

cagcagatcg agaacatccg gagcccagag ggcagccgca agaaccccgc ccgcacctgc 300

cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac 360

caaggctgca acctggatgc catcaaagtc ttctgcaaca tggagactgg tgagacctgc 420

gtgtacccca ctcagcccag tgtggcccag aagaactggt acatcagcaa gaaccccaag 480

gacaagaggc atgtctggtt cggcgagagc atgaccgatg gattccagtt cgagtatggc 540

ggccagggct cccaccctgc cgatgtggac ctccggccgc gaccaccctt 590

216

tngagcggcc gcccgggcag gntgnnaacg ctggtcctgc tggtcctcct ggcaaggctg 60

gtgaagatgg tcaccctgga aaacccggac gacctggtga gagaggagtt gttggaccac 120

agggtgctcg tggtttccct ggaactcctg gacttcctgg cttcaaaggc attaggggac 180

acaatggtct ggatggattg aagggacagc ccggtgctcc tggtgtgaag ggtgaacctg 240

gtgcccctgg tgaaaatgga actccaggtc aaacaggagc ccgtgggctt cctggtgaga 300

gaggaccgtg ttggtgcccc tggcccanac ctcggccgcg accacgctaa gcccgaattt 360

ccagcacact ggnggccgtt actantggat ccgagctcgg taccaagctt ggcgtaatca 420

tggtcatagc tgtttcctgn gtgaaattgt tatccgctca caatttcaca cancatacga 480

agccggaaag cataaagtgt aaagccttgg ggtgctaatg agtgagctaa ctcncattaa 540

attgcgttgc gctcactgcc cgcttttcca nnngggaaac cntggcntng ccngcttgcn 600

ttaantgaaa tccgccnacc cccggggaaa agncggtttg cngtattggg gcnctttttc 660

cctttcctcg gnttacttga nttantgggc tttggncgnt tcgggttgng gcgancnggt 720

tcaacntcac nccaaaggng gnaanacggt tttcccanaa tccgggggnt ancccaangn 780

aaaacatnng ncnaangggc t 801

217

agcgtggttn gcggccgagg tctgggccag gggcaccaac acgtcctctc tcaccaggaa 60

gcccacgggc tcctgtttga cctggagttc cattttcacc aggggcacca ggttcaccct 120

tcacaccagg agcaccgggc tgtcccttca atccatncag accattgtgn cccctaatgc 180

ctttgaagcc aggaagtcca ggagttccag ggaaaccacc gagcaccctg tggtccaaca 240

actcctctct caccaggtcg tccgggtttt ccagggtgac catcttcacc agccttgcca 300

ggaggaccag caggaccagc gttaccaacc tgcccgggcg gccgctcga 349

218

372

Homo sapien

218

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360

cgcgaccacg ct 372

219

374

Homo sapien

219

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttaggct ttggaagtgg tcatttcaag atgtgattca tctagatggt gccatgacaa 300

tggtgtgaac tacaagattg gagagaagtg ggaccgtcag ggagaaaatg gacctgcccg 360

ggccggccgc tcga 374

220

tcgagcgnnc gcccgggcag gtccagtagt gccttcggga ctgggttcac ccccaggtct 60

gcggcagttg tcacagcgcc agccccgctg gcctccaaag catgtgcagg agcaaatggc 120

accgagatat tccttctgcc actgttctcc tacgtggtat gtcttcccat catcgtaaca 180

cgttgcctca tgagggtcac acttgaattc tccttttccg ttcccaagac atgtgcagct 240

catttggctg gctctatagt ttggggaaag tttgttgaaa ctgtgccact gacctttact 300

tcctccttct ctactggagc tttcgtacct tccacttctg ctgttggtaa aatggtggat 360

cttctatcaa tttcattgac agtacccact tctcccaaac atccagggaa atagtgattt 420

cagagcgatt aggagaacca aattatgggg cagaaataag gggcttttcc acaggttttc 480

ctttggagga agatttcagt ggtgacttta aaagaatact caacagtgtc ttcatcccca 540

tagcaaaaga agaaacngta aatgatggaa ngcttctgga gatgccnnca tttaagggac 600

ncccagaact tcaccatcta caggacctac ttcagtttac annaagncac atantctgac 660

tcanaaagga cccaagtagc nccatggnca gcactttnag cctttcccct ggggaaaann 720

ttacnttctt aaancctngg ccnngacccc cttaagncca aattntggaa aanttccntn 780

cnnctggggg gcngttcnac atgcntttna agggcccaat tnccccnt 828

221

476

Homo sapien

221

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt 180

acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg 240

ggagggcttt gttggagacc ttgcacttgt actccttgcc attcagccag tcctggtgca 300

ggacggtgag gacgctgacc acacggtacg tgctgttgta ctgctcctcc cgcggctttg 360

tcttggcatt atgcacctcc acgccgtcca cgtaccagtt gaacttgacc tcagggtctt 420

cgtggctcac gtccaccacc acgcatgtaa cctcagacct cggccgcgac cacgct 476

222

477

Homo sapien

222

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 180

ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc 240

ccccatcgag aaaaccatct ccaaagccaa agggcaagcc ccgagaacca caggtgtaca 300

ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc tgcctggtca 360

aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag ccggagaaca 420

actacaagac cacgcctccc gtgctggact ccgacacctg cccgggcggc cgctcga 477

223

361

Homo sapien

223

tcgagcggcc gcccgggcag gttgaatggc tcctcgctga ccaccccggt gctggtggtg 60

ggtacagagc tccgatgggt gaaaccattg acatagagac tgtccctgtc cagggtgtag 120

gggcccagct cagtgatgcc gtgggtcagc tggctcagct tccagtacag ccgctctctg 180

tccagtccag ggcttttggg gtcaggacga tgggtgcaga cagcatccac tctggtggct 240

gccccatcct tctcaggcct gagcaaggtc agtctgcaac cagagtacag agagctgaca 300

ctggtgttct tgaacaaggg cataagcaga ccctgaagga cacctcggcc gcgaccacgc 360

t 361

224

361

Homo sapien

224

agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca 60

gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg 120

cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg 180

acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc 240

cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac 300

ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg 360

a 361

225

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg tcccggttcc aggccagtaa tagtagcctc 540

tgtgacacca gggcggggcc gagggaccct tctnttggaa gagaccagct tctcatactt 600

gatgatgagn ccggtaatcc tggcacgtgg nggttgcatg atnccaccaa ggaaatnggn 660

gggggnggac ctgcccggcg gccgttcnaa agcccaattc cacacacttg gnggccgtac 720

tatggatccc actcngtcca acttggngga atatggcata actttt 766

226

364

Homo sapien

226

tcgagcggcc gcccgggcag gtccttgacc ttttcagcaa gtgggaaggt gtaatccgtc 60

tccacagaca aggccaggac tcgtttgtac ccgttgatga tagaatgggg tactgatgca 120

acagttgggt agccaatctg cagacagaca ctggcaacat tgcggacacc ctccaggaag 180

cgagaatgca gagtttcctc tgtgatatca agcacttcag ggttgtagat gctgccattg 240

tcgaacacct gctggatgac cagcccaaag gagaaggggg agatgttgag catgttcagc 300

agcgtggctt cgctggctcc cactttgtct ccagtcttga tcagacctcg gccgcgacca 360

cgct 364

227

275

Homo sapien

227

agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt 60

ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa 120

gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac 180

atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg 240

catccccctt ccaaacctgc ccgggcggcc gctcg 275

228

275

Homo sapien

228

cgagcggccg cccgggcagg tttggaaggg ggatgcgggg gaagaggaag actgacggtc 60

cccccaggag ttcaggtgct gggcacggtg ggcatgtgtg agttttgtca caagatttgg 120

gctcaactct cttgtccacc ttggtgttgc tgggcttgtg atctacgttg caggtgtagg 180

tctgggtgcc gaagttgctg gagggcacgg tcaccacgct gctgagggag tagagtcctg 240

aggactgtag gacagacctc ggccgcgacc acgct 275

229

nggnnggtcc ggncngncag gaccactcnt cttcgaaata 40

230

208

Homo sapien

230

agcgtggtcg cggccgaggt cctcacttgc ctcctgcaaa gcaccgatag ctgcgctctg 60

gaagcgcaga tctgttttaa agtcctgagc aatttctcgc accagacgct ggaagggaag 120

tttgcgaatc agaagttcag tggacttctg ataacgtcta atttcacgga gcgccacagt 180

accaggacct gcccgggcgg ccgctcga 208

231

tcgagcggcc gcccgggcag gtcctggtac tgnggcgctc cgtgaaatta gacgttatca 60

gaagtccact gaacttctga ttcgcaaact tcccttccag cgtctggtgc gagaaattgc 120

tcaggacttt aaaacagatc tgcgcttcca gagcgcagct atcggtgctt tgcaggaggc 180

aagtgaggac ctcggccgcg accacgct 208

232

332

Homo sapien

232

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

233

gtgggnttga acccntttna nctccgcttg gtaccgagct cggatccact agtaacggcc 60

gccagtgtgc tggaattcgg cttagcgtgg tcgcggccga ggtcaagaac cccgcccgca 120

cctgccgtga cctcaagatg tgccactctg actggaagag tggagagtac tggattgacc 180

ccaaccaagg ctgcaacctg gatgccatca aagtcttctg caacatggag actggtgaga 240

cctgcgtgta ccccactcag cccagtgtgg cccagaagaa ctggtacatc agcaagaacc 300

ccaaggacaa gaggcatgtc tggttcggcg agagcatgac cgatggattc cagttcgagt 360

atggcggcca gggctccgac cctgccgatg tggacctgcc cgggcggccg ctcga 415

234

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa 420

ggcttgcagc ccacagtgga gtatgtggtt aagtgtctat gctcagaatc caagcggaga 480

gaagtcagcc tctggttcag actgnaagta accaacattg atcgcctaaa ggactggcat 540

tcactgatgn ggatgccgat tccatcaaaa ttgnttggga aaacccacag gggcaagttt 600

ncangtcnag gnggacctac tcgagccctg aggatggaat ccttgactnt tccttnncct 660

gatggggaaa aaaaaccttn aaaacttgaa ggacctgccc gggcggccgt ncaaaaccca 720

attccacccc cttgggggcg ttctatgggn cccactcgga ccaaacttgg ggtaan 776

235

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg gcatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttagttttt gttggtcctg gtccattttt 360

gggagtggtg gttactctgt aaccagtaac aggggaactt gaaggcagcc acttgacact 420

aatgctgttg tcctgaacat cggtcacttg catctgggat ggtttgtcaa tttctgttcg 480

gtaattaatg gaaattggct tgctgcttgc ggggcttgtc tccacggcca gtgacagcat 540

acacagtgat ggtataatca actccaggtt taagccgctg atggtagctg aaactttgct 600

ccaggcacaa gtgaactcct gacagggcta tttcctnctg ttctccgtaa gtgatcctgt 660

aatatctcac tgggacagca ggangcattc caaaacttcg ggcgngaccc cctaagccga 720

attntgcaat atncatcaca ctggcgggcg ctcgancatt cattaaaagg cccaatcncc 780

cctataggga gtntantaca attng 805

236

262

Homo sapien

236

tcgagcggcc gcccgggcag gtcacttttg gtttttggtc atgttcggtt ggtcaaagat 60

aaaaactaag tttgagagat gaatgcaaag gaaaaaaata ttttccaaag tccatgtgaa 120

attgtctccc atttttttgg cttttgaggg ggttcagttt gggttgcttg tctgtttccg 180

ggttgggggg aaagttggtt gggtgggagg gagccaggtt gggatggagg gagtttacag 240

gaagcagaca gggccaacgt cg 262

237

372

Homo sapien

237

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttaggct ttggaagtgg tcatttcaga tgtgattcat ctagatggtg ccatgacaat 300

ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg acctgcccgg 360

gcggccgctc ga 372

238

372

Homo sapien

238

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360

cgcgaccacg ct 372

239

tcgagcggcc gcccgggcag gtccaccata agtcctgata caaccacgga tgagctgtca 60

ggagcaaggt tgatttcttt cattggtccg gtcttctcct tgggggtcac ccgcactcga 120

tatccagtga gctgaacatt gggtggtgtc cactgggcgc tcaggcttgt gggtgtgacc 180

tgagtgaact tcaggtcagt tggtgcagga atagtggtta ctgcagtctg aaccagaggc 240

tgactctctc cgcttggatt ctgagcatag acactaacca catactccac tgtgggctgc 300

aagccttcaa tagtcatttc tgtttgatct ggacctgcag ttttagtttt tgttggtcct 360

ggtccatttt tgggagtggt ggttactctg taaccagtaa caggggaact tgaaggcagc 420

cacttgacac taatgctgtt gtcctgaaca tcggtcactt gcatctggga tggtttgnca 480

atttctgttc ggtaattaat ggaaattggc ttgctgcttg cggggctgtc tccacggcca 540

gtgacagcat acacagngat ggnatnatca actccaagtt taaggccctg atggtaactt 600

taaacttgct cccagccagn gaacttccgg acagggtatt tcttctggtt ttccgaaagn 660

gancctggaa tnntctcctt ggancagaag gancntccaa aacttgggcc ggaacccctt 720

240

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg ttcccggttc caggccagta atagtagcct 540

cttgtgacac caggcggggc ccanggacca cttctctggg angagaccca gcttctcata 600

cttgatgatg taacccggta atcctgcacg tggcggctgn catgatacca ncaaggaatt 660

gggtgnggng gacctgcccg gcggccctcn a 691

241

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa 420

ggcttgcagc ccacagtgga gtatgtggtt agtgtctatg ctcagaatcc aagcggagag 480

agtcagcctc tggttcagac tgcagtaacc actattcctg caccaactga cctgaagttc 540

actcaggtca cacccacaag cctgagccgc cagtggacac cacccaatgt tcactcactg 600

gatatcgagt gcgggtgacc cccaaggaga agacccggac ccatgaaaga aatcaacctt 660

gctcctgaca gctcatccgn gggtgtatca ggacttatgg gggactgccc cggcnggccg 720

ntcgaaancg aattntgaaa tttccttcnc actgggnggc gnttcgagct tncttntana 780

nggcccaatt cncctntagn gggtcgtn 808

242

agcgtggtcg cggccgaggt cnagga 26

243

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgaggaacat ggttttaggc ggaccacacc gcccacaacg 480

ggcaccccca taaggnatag gccaagacca taccccgccg aatgtaggac aagaagctct 540

ntctcaacaa ccatctcatg ggccccattc caggacactt ctgagtacat catttcatgt 600

catcctggtg ggcacttgat gaanaaccct tacagttcag ggttcctgga acttctacca 660

gngccacttc tgacagganc ttgggcgnga ccaccct 697

244

373

Homo sapien

244

agcgtggtcg cggccgaggt ccattttctc cctgacggtc ccacttctct ccaatcttgt 60

agttcacacc attgtcatgg caccatctag atgaatcaca tctgaaatga ccacttccaa 120

agcctaagca ctggcacaac agtttaaagc ctgattcaga cattcgttcc cactcatctc 180

caacggcata atgggaaact gtgtaggggt caaagcacga gtcatccgta ggttggttca 240

agccttcgtt gacagagttg cccacggtaa caacctcttc ccgaacctta tgcctctgct 300

ggtctttcag tgcctccact atgatgttgt aggtggcacc tctggtgagg acctgcccgg 360

gcggcccgct cga 373

245

307

Homo sapien

245

246

372

Homo sapien

246

tcgagcggcc gcccgggcag gtcctcacca gaggtgccac ctacaacatc atagtggagg 60

cactgaaaga ccagcagagg cataaggttc gggaagaggt tgttaccgtg ggcaactctg 120

tcaacgaagg cttgaaccaa cctacggatg actcgtgctt tgacccctac acagtttccc 180

attatgccgt tggagatgag tgggaacgaa tgtctgaatc aggctttaaa ctgttgtgcc 240

agtgcttagg ctttggaagt ggtcatttca gatgtgattc atctagatgg tgccatgaca 300

atggtgtgaa ctacaagatt ggagagaagt gggaccgtca gggagaaaat ggacctcggc 360

cgcgaccacg ct 372

247

tcgagcggcc gcccgggcag gtaccggggt ggtcagcgag gagccattca cactgaactt 60

caccatcaac aacctgcggt atgaggagaa catgcagcac cctggctcca ggaagttcaa 120

caccacggag agggtccttc agggcctgct caggtccctg ttcaagagca ccagtgttgg 180

ccctctgtac tctggctgca gactgacttt gctcagacct gagaaacatg gggcagccac 240

tggagtggac gccatctgca ccctccgcct tgatcccact ggtnctggac tggacanana 300

gcggctatac ttgggagctg anccnaacct ttggcggnga cnccnctt 348

248

gaggactggc tcagctccca gtatagccgc tctctgtcca gtccaggacc agtgggatca 60

aggcggaggg tgcagatggc gtccactcca gtggctgccc catgtttctc aagtctgagc 120

aaagncagtc tgcagccaga gtacagaggg ccaacactgg tgctcttgaa cagggacctg 180

agcaggccct gaaggaccct ctccgtggtg ttgaacttcc tggagccagg gtgctgcatg 240

ttctcctcat accgcaggtt gttgatggtg aagttcagtg tgaatggctc ctcgctgacc 300

accc 304

249

agcgtggtcg cggccgaggt ccaccacacc caattccttg ctggtatcat ggcagccgcc 60

acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga 120

agtggtccct cggccccgcc ctggtgtcac agaggctact attactggcc tggaaccggg 180

aaccgaatat acaatttatg tcattgccct gaagaataat cagaagagcg agcccctgat 240

tggaaggaaa aagacagacg agcttcccca actggtaacc cttccacacc ccaatcttca 300

tggaccanan ancttggatn gtcctttcac nggttnaaaa aacccttttc gcccccccac 360

cttggggatt aaccttggga aanggggatt tnaccnttcc 400

250

tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct 60

gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt 120

gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg 180

cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct 240

aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc 300

aggaagctga ataccatttc cagtgtcata cccagggngg gtgaccaaag ggggtcnttt 360

ngacctggng aaaggaacca tccaaaanct ctgncccatg 400

251

agcgtggncg cggccgaggt ctgaggatgt aaactcttcc caggggaagg ctgaagtgct 60

gaccatggtg ctactgggtc cttctgagtc agatatgtga ctgatgngaa ctgaagtagg 120

tactgtagat ggtgaagtct gggtgtccct aaatgctgca tctccagagc cttccatcat 180

taccgtttct tcttttgcta tgggatgaga cactgttgag tattctctaa agtcaccact 240

gaaatcttcc tccaaaggaa aacctgtgga aaagcccctt atttctgccc cataatttgg 300

ttctcctaat cnctctgaaa tcactatttc cctggaangt ttgggaaaaa nngggcnacc 360

tgncantgga aantggatan aaagatccca ccattttacc caacnagcag aaagtgggaa 420

nggtaccgaa aagctccaag taanaaaaag gagggaagta aaggtcaagt gggcaccagt 480

ttcaaacaaa actttcccca aactatanaa ccca 514

252

aagcggccgc ccgggcaggn ncagnagtgc cttcgggact gggntcaccc ccaggtctgc 60

ggcagttgtc acagcgccag ccccgctggc ctccaaagca tgtgcaggag caaatggcac 120

cgagatattc cttctgccac tgttctccta cgtggtatgt cttcccatca tcgtaacacg 180

ttgcctcatg agggtcacac ttgaattctc cttttccgtt cccaagacat gtgcagctca 240

tttggctggc tctatagttt ggggaaagtt tgttgaaact gtgccactga cctttacttc 300

ctccttctct actggagctt tccgtacctt ccacttctgc tgntggnaaa aagggnggaa 360

cntcttatca atttcattgg acagtanccc nctttctncc caaaacatnc aagggaaaat 420

attgattncn agagcggatt aaggaacaac ccnaattatg ggggccagaa ataaaggggg 480

cttttccaca ggtnttttcc t 501

253

226

Homo sapien

253

tcgagcggcc gcccgggcag gtctgcaggc tattgtaagt gttctgagca catatgagat 60

aacctgggcc aagctatgat gttcgatacg ttaggtgtat taaatgcact tttgactgcc 120

atctcagtgg atgacagcct tctcactgac agcagagatc ttcctcactg tgccagtggg 180

caggagaaag agcatgctgc gactggacct cggccgcgac cacgct 226

254

226

Homo sapien

254

agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt 60

gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg 120

catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct 180

cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga 226

255

cgagcggccg cccgggcagg tccagactcc aatccagaga accaccaagc cagatgtcag 60

aagctacacc atcacaggtt tacaaccagg cactgactac aagatctacc tgtacacctt 120

gaatgacaat gctcggagct cccctgtggt catcgacgcc tccactgcca ttgatgcacc 180

atccaacctg cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc 240

acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga 300

agtggtccct cggccccgcc ctggtgncac agaagctact attactggcc tggaaccggg 360

aaccgaatat acaatttatg tcattgccct gaagaataat canaagagcg agcccctgat 420

tggaagg 427

256

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct gtctttttcc 180

ttccaatcag gggctcgctc ttctgattat tcttcagggc aatgacataa attgtatatt 240

cggttcccgg ttccaggcca gtaatagtag cctctgtgac accagggcgg ggccgaggga 300

ccacttctct gggaggagac ccaggcttct catacttgat gatgtanccg gtaatcctgg 360

caccgtggcg gctgccatga taccagcaag gaattgggtg tggtggccaa gaaacgcagg 420

ttggatggtg catcaatggc agtggaggcg tcgatnacca caggggagct ccgancattg 480

tcattcaagg tggacaggta gaatcttgta atcaggtgcc tggtttgtaa acctg 535

257

tcgagcggcc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag 60

agcctgagcc agcagatcga gaacatccgg agcccagagg gcagccgcaa gaaccccgcc 120

cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt 180

gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt 240

gagacctgcg tgtaccccac tcagcccagt gtggcccaga agaactggta catcagcaag 300

aaccccaagg acaagaagca tgtctggttc ggcgaaagca tgaccgatgg attccagttc 360

gagtatggcg gccagggctc cgaccctgcc gatgtggacc tcggccgcga ccacgctaag 420

cccgaattcc agcacactgg cggccgttac tagtgggatc cgagcttcgg taccaagctt 480

ggcgtaatca tgggncatag ctgtttcctg ngtgaaaatg gtattccgct tcacaatttc 540

ccac 544

258

418

Homo sapien

258

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc 300

ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaagctctt 360

gaagggtggt gtccacctcg aggtcacggt cacgaaacct gcccgggcgg ccgctcga 418

259

agcgtggtcg cggccgaggt caagaacccc gcccgcacct gccgtgacct caagatgtgc 60

cactctgact ggaagagtgg agagtactgg attgacccca accaaggctg caacctggat 120

gccatcaaag tcttctgcaa catggagact ggtgagacct gcgtgtaccc cactcagccc 180

agtgtggccc agaagaactg gtacatcagc aagaacccca aggacaagag gcatgtctgg 240

ttcggcgaga gcatgaccga tggattccag ttcgagtatg gcggccaggg ctccgaccct 300

gccgatgtgg acctgcccgn gccggnccgc tcgaaaagcc cnaatttcca gncacacttg 360

gccggccgtt actactg 377

260

332

Homo sapien

260

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

261

94

Homo sapien

261

cgagcggccg cccgggcagg tcccccccct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt tttt 94

262

agcgtggtcg cggccgaggt ctggcattcc ttcgacttct ctccagccga gcttcccaga 60

acatcacata tcactgcaaa aatagcattg catacatgga tcaggccagt ggaaatgtaa 120

agaaggccct gaagctgatg gggtcaaatg aaggtgaatt caaggctgaa ggaaatagca 180

aattcaccta cacagttctg gaggatggtt gcacgaaaca cactggggaa tggagcaaaa 240

cagtctttga atatcgaaca cgcaaggctg tgagactacc tattgtagat attgcaccct 300

atgacattgg tggtcctgat caagaatttg gtgtggacgt tggccctgtt tgctttttat 360

aaaccaaact ctatctgaaa tcccaacaaa aaaaatttaa ctccatatgt gntcctcttg 420

ttctaatctt ggcaaccagt gcaagtgacc gacaaaattc cagttattta tttccaaaat 480

gtttggaaac agtataattt gacaaagaaa aaaggatact tctctttttt tggctggtcc 540

accaaataca attcaaaagg ctttttggtt ttattttttt anccaattcc aatttcaaaa 600

tgtctcaatg gngcttataa taaaataaac tttcaccctt nttttntgat 650

263

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagaa gtaaccacca ctcccaaaaa 360

tggaccagga ccaacaaaaa ctaaaactgc aggtccagat caaacagaaa atggactatt 420

gaaggcttgc agcccacagt ggaagtatgt ggntaggngt ctatgctcag aatcccaagc 480

cggagaaagt cagccttctg gtttagactg cagtaaccaa cattgatcgc cctaaaggac 540

tggncattca cttggatggt ggatgtccaa ttc 573

264

tcgagcggcc gcccgggcag gtccttgcag ctctgcagng tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagngaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttaagtttt tggtggtcct gncccatttt 360

tgggaagtgg ggggttactc tgtaaccagt aacaggggaa cttgaaggca gccacttgac 420

actaatgctg ttgtcctgaa catcggtcac ttgcatctgg ggatggtttt gacaatttct 480

ggttcggcaa attaatggaa attggcttgc tgcttggcgg ggctgnctcc acgggccagt 540

gacagcatac 550

265

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttaagtttt tgttggncct gnnccatttt 360

tggggaaggg gtggttactc ttgtaaccag taacagggga acttgaagca gccacttgac 420

actaatgctg gtggcctgaa catcggtcac ttgcatctgg gatggtttgg tcaatttctg 480

ttcggtaatt aatgggaaat tggcttactg gcttgcgggg gctgtctcca cggncagtga 540

caagcataca caggngatgg gtataatcaa ctccaggttt aaggccnctg atggta 596

266

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agtaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

gggaccagga ccaacaaaaa actaaaactg canggtccag atcaaacaga aatgactatt 420

gaaggcttgc agcccacagt ggagtatgtg ggttagtgtc tatgctcaga atnccaagcg 480

gagagagtca gcctctggtt cagact 506

267

tcgagcggcc gcccgggcag gtcagcgctc tcaggacgtc accaccatgg cctgggctct 60

gctcctcctc accctcctca ctcagggcac agggtcctgg gcccagtctg ccctgactca 120

gcctccctcc gcgtccgggt ctcctggaca gtcagtcacc atctcctgca ctggaaccag 180

cagtgacgtt ggtgcttatg aatttgtctc ctggtaccaa caacacccag gcaaggcccc 240

caaactcatg atttctgagg tcactaagcg gccctcaggg gtccctgatc gcttctctgg 300

ctccaagtct ggcaacacgg cctccctgac cgtctctggg ctccangctg aggatgangc 360

tgattattac tggaagctca tatgcaggca acaacaattg ggtgttcggc ggaagggacc 420

aagctgaccg tnctaaggtc aagcccaagg cttgcccccc tcggtcactc tgttcccacc 480

ctcctctgaa gaagctttca agccaacaan gncacactgg gtgtgtctca taagtggact 540

ttctaccc 548

268

agcgtggtcg cggccgaggt ctgtagcttc tgtgggactt ccactgctca ggcgtcaggc 60

tcaggtagct gctggccgcg tacttgttgt tgctttgntt ggagggtgtg gtggtctcca 120

ctcccgcctt gacggggctg ctatctgcct tccaggccac tgtcacggct cccgggtaga 180

agtcacttat gagacacacc agtgtggcct tgttggcttg aagctcctca gaggagggtg 240

ggaacagagt gaccgagggg gcagccttgg gctgacctag gacggtcagc ttggtccctc 300

cgccgaacac ccaattgttg ttgcctgcat atgagctgca gtaataatca gcctcatcct 360

cagcctggag cccagagacn gtcaagggag gcccgtgttt gccaagactt ggaagccaga 420

naagcgatca gggacccctg agggccgctt tacngacctc aaaaaatcat gaatttgggg 480

ggcctttgcc tgggngttgg ttggtnacca gnaaaacaaa atttcataaa gcaccaacgt 540

cactgctggt ttccagtgca ngaanatggt gaactgaant gtcc 584

269

agcgtggtcg cggccgaggt ccagcatcag gagccccgcc ttgccggctc tggtcatcgc 60

ctttcttttt gtggcctgaa acgatgtcat caattcgcag tagcagaact gccgtctcca 120

ctgctgtctt ataagtctgc agcttcacag ccaatggctc ccatatgccc agttccttca 180

tgtccaccaa agtacccgtc tcaccattta caccccaggt ctcacagttc tcctgggtgt 240

gcttggcccg aagggaggta agtanacgga tggtgctggt cccacagttc tggatcaggg 300

tacgaggaat gacctctagg gcctgggcna caagccctgt atggacctgc ccgggcgggc 360

ccgctcga 368

270

tcgagcggcc gcccgggcag gtccatacag ggctgttgcc caggccctag aggncattcc 60

ttgtaccctg atccagaact gtgggaccag caccatccgt ctacttacct cccttcgggc 120

caagcacacc caggagaact gtgagacctg gggtgtaaat ggngagacgg gtactttggt 180

ggacatgaag gaactgggca tatgggagcc attggctgng aagctgcana cttataagac 240

agcagtggag acggcagttc tgctactgcg aattgatgac atcgtttcag gccacaaaaa 300

gaaaggcgat gaccanagcc ggcaaggcgg ggcttcctga tgctggacct cggccgccga 360

ccacgctt 368

271

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgggaaac tccgaggaca 180

gagggctaaa tccatgaagt ttgtggatgg cctgatgatc cacagcggag accctgttaa 240

ctactacgtt gacactgctg tgcgccacgt gttgctcana cagggtgtgc tgggcatcaa 300

ggtgaagatc atgctgccct gggacccanc tggcaaaaat ggcccttaaa aaccccttgc 360

cntgaccacg tgaaccattt gtgngaaccc caagatgaan atacttgccc accacccccc 420

attc 424

272

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacag cagtgtcaac gtagtagtta acagggtctc cgctgtggat 300

catcaggcca tccacaaact tcatggattt agccctctgt cctcggagtt tcccaaaaca 360

ccacaacctc gccagccttt gggccccact tcttcatgaa tgaaaccgca gcacaccatt 420

ancaaggccc ttccgcacag gnaagccctt cctaaggagt tttgtaaacg caaaaaactc 480

ttgcctgggg caaatgggca cacagacctn tantnggacc ttggnccgcg aaccaccgct 540

t 541

273

agcgtggtcg cggccgaggt ctggccctcc tggcaaggct ggtgaagatg gtcaccctgg 60

aaaacccgga cgacctggtg agagaggagt tgttggacca cagggtgctc gtggtttccc 120

tggaactcct ggacttcctg gcttcaaagg cattagggga cacaatggtc tggatggatt 180

gaagggacag cccggtgctc ctggtgtgaa gggtgaacct ggngcccctg gtgaaaatgg 240

aactccaggt caaacaggag cccgngggct tcctggngag agaggacgtg ttggtgcccc 300

tggcccanac ctgcccgggc ggccgctcna aaagccgaaa tccagnacac tggcggccgn 360

tactantgga atccgaactt cggtaccaaa gcttggccgt aatcatggcc atagcttgtt 420

ccctggggng gaaattggta ttccgctncc aattccacac aacataccga acccggaaag 480

cattaaagtg taaaagccct gggggggcct aaatgangtg agcntaactc ncatttaatt 540

ggcgttgcgc ttcactgccc cgcttttcca gtccgggna 579

274

tcgagcggcc gcccgggcag gtctgggcca ggggcaccaa cacgtcctct ctcaccagga 60

agcccacggg ctcctgtttg acctggagtt ccattttcac caggggcacc aggttcaccc 120

ttcacaccag gagcaccggg ctgtcccttc aatccatcca gaccattgtg ncccctaatg 180

cctttgaagc caggaagtcc aggagttcca gggaaaccac gagcaccctg tggtccaaca 240

actcctctct caccaggtcg tccgggtttt ccagggtgac catcttcacc agccttgcca 300

ggagggccag acctcggccg cgaccacgct 330

275

ancgtggtcg cggccgaggt cctcaccaga ggtgncacct acaacatcat agtggaggca 60

ctgaaagacc ancagaggca taaggttcgg gaagagg 97

276

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgtccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcngn 360

ccngaacaac gcttaagccc gnattctgca gaataatccc atcacacttg gcggccgctt 420

cgancatgca tcntaaaagg ggccccaatt tcccccttat aagngaancc gtatttncca 480

atttcactgg ncccgccgnt tttacaaacg ncggtgaact ggggaaaaac cctggcggtt 540

acccaacttt aatcgccntt ggcagcacaa tccccccttt tcgnccancn tgggcgtaaa 600

taaccgaaaa 610

277

ancgnggtcg cggccgangt nttttttctt nttttttt 38

278

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgggnggtc agcgtcctca ccgtcctgca 180

ccagaattgg ttgaatggca aggagtacaa gngcaaggtt tccaacaaag ccntcccagc 240

ccccntcgaa aaaaccattt ccaaagccaa agggcagccc cgagaaccac aggtgtacac 300

cctgccccca tcccgggagg aaaagancaa naaccnggtt cagccttaac ttgcttggtc 360

naangctttt tatcccaacg nacttccccc ntggaantgg gaaaaaccaa tgggccaanc 420

cgaaaaacaa ttacaanaac ccc 443

279

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtga 180

acacctgggg ttctcggggc ttgccctttg gttttgaana tggttttctc gatgggggct 240

ggaagggctt tgttgnaaac cttgcacttg actccttgcc attcacccag ncctggngca 300

ggacggngag gacnctnacc acacggaacc gggctggtgg actgctcc 348

280

agcgtggtcg cggacgangt cctgtcagag tggnactggt agaagttcca ngaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagngn 120

cctggaatgg ggcccatgan atggttgcc 149

281

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cggcaccccc 360

cctgggtatg aacctgggaa aanggnantt aanctttcct ggca 404

282

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaaggtn ccctggtact gggttacaga ntaaccacca ctcccaaaaa 360

tggaccagga accacaaaaa cttaaactgc agggtccaga tcaaaacaga aatgactatt 420

gaangcttgc agcccacagt gggagtatgn gggtagtgnc tatgcttcag aatccaagcg 480

gaaaaangtc aagccttntg ggttcaa 507

283

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagnctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca anccttcaat 300

aanncatttc tgtttgatct ggacc 325

284

tcgagcggcc gcccgggcag gtctggtggg gtcctggcac acgcacatgg gggngttgnt 60

ctnatccagc tgcccagccc ccattggcga gtttgagaag gtgtgcagca atgacaacaa 120

naccttcgac tcttcctgcc acttctttgc cacaaagtgc accctggagg gcaccaagaa 180

gggccacaag ctccacctgg actacatcgg gccttgcaaa tacatccccc cttgcctgga 240

ctctgagctg accgaattcc cccttgcgca tgcgggactg gctcaagaac cgtcctggca 300

cccttgtatg anagggatga agacacnacc c 331

285

agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt 60

ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa 120

gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac 180

atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg 240

catccccctt ccaaacctgc ccgggcggcc gctcgaaagc cgaattccag cacactggcg 300

gccggtacta gtgganccna acttggnanc caacctggng gaantaatgg gcataanctg 360

tttctggggg gaaattggta tccngtttac aattcccnca caacatacga gccggaagca 420

taaaagngta aaagcctggg ggnggcctan tgaagtgaag ctaaactcac attaattngc 480

gttgccgctc actggcccgc ttttccagc 509

286

tcgagcggcc gcccgggcag gtttggaagg gggatgcggg ggaagaggaa gactgacggt 60

ccccccagga gttcaggtgc tgggcacggt gggcatgtgt gagttttgtc acaagatttg 120

ggctcaactc tcttgtccac cttggtgttg ctgggcttgt gatctacgtt gcaggtgtag 180

gtctgggngc cgaagttgct ggagggcacg gtcaccacgc tgctgaggga gtagagtcct 240

gaggactgta ngacagacct cggccgngac cacgctaagc cgaattctgc agatatccat 300

cacactggcg gccgctccga gcatgcattt tagagg 336

287

agcgtggncg cggacganga caacaacccc 30

288

tcgagcggcc gcccgggcag gnccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctcttgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgn accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacct 316

289

agcgtggtcg cggccgaggt ccagcctgga gataanggtg aaggtggtgc ccccggactt 60

ccaggtatag ctggacctcg tggtagccct ggtgagagag gtgaaactgg ccctccagga 120

cctgctggtt tccctggtgc tcctggacag aatggtgaac ctggnggtaa aggagaaaga 180

ggggctccgg ntganaaagg tgaaggaggc cctcctgnat tggcaggggc cccangactt 240

agaggtggag ctggcccccc tggccccgaa ggaggaaagg gtgctgctgg tcctcctggg 300

ccacctgg 308

290

tcgagcggcc gcccgggcag gtctgggcca ggaggaccaa taggaccagt aggacccctt 60

gggccatctt tccctgggac accatcagca cctggaccgc ctggttcacc cttgtcaccc 120

tttggaccag gacttccaag acctcctctt tctccaggca ttccttgcag accaggagta 180

ccancagcac caggtggccc aggaggacca gcagcaccct ttcctccttc gggaccaggg 240

ggaccagctc cacctctaag tcctggggcc cctgccaatc caggagggcc tccttcacct 300

ttctcacccg gagcccctct ttct 324

291

tcgagcggcc gcccgggcag gtccaccggg atattcgggg gtctggcagg aatgggaggc 60

atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac 120

agagtgagga gcctggagac cgacaaccgg aggctggaga gcaaaatccg ggagcacttg 180

gagaagaagg gaccccaggt cagagactgg agccattact tcaagatcat cgaggacctg 240

agggctcana tcttcgcaaa tactgcngac aatgcccg 278

292

atgcgnggtc gcggccgang accanctctg gctcatactt gactctaaag ncntcaccag 60

nanttacggn cattgccaat ctgcagaacg atgcgggcat tgtccgcant atttgcgaag 120

atctgagccc tcaggncctc gatgatcttg aagtaanggc tccagtctct gacctggggt 180

cccttcttct ccaagtgctc ccggattttg ctctccagcc tccggttctc ggtctccaag 240

ncttctcact ctgtccagga aaagaggcca ggcggncgat cagggctttt gcatggact 299

293

101

Homo sapien

293

agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt tttttttttt t 101

294

tcgagcggcc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca 60

gttngtgtgc ggggaggtaa caagaaatac cgtgccctga ggntggacgn ggggaatttc 120

tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca 180

tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatngac 240

agcacaccgt accgacagtg ggtaccgaag tcccactatg cncct 285

295

216

Homo sapien

295

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaag 216

296

agcgtgntcn cggccgagga tggggaagct cgnctgtctt tttccttcca atcaggggct 60

nnntcttctg attattcttc agggcaanga cataaattgt atattcggnt cccggttcca 120

gnccagtaat agtagcctct gtgacaccag ggcggggccg agggaccact tctctgggag 180

gagacccagg cttctcatac ttgatgatga agccggtaat cctggcacgt gggcggctgc 240

catgatacca ccaangaatt gggtgtggtg gacctgcccg ggcgggccgc tcgaaaancc 300

gaattcntgc aagaatatcc atcacacttg ggcgggccgn tcgaaccatg catcntaaaa 360

gggccccaat ttccccccta ttaggngaag ccncatttaa caaattccac ttgg 414

297

tcgagcggcc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggtccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagccttgag 240

ccagcagaat cgaaaacatt cggaacccaa gaagggcaag cccgcaaaga aaccccgccc 300

gcacctggcc gngaacctcc aagaangtgc ccacntcttg actgggaaaa aaagggaaaa 360

ntacttggaa ttggac 376

298

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagaagt ggcacatctt gaggtcacgg cagggtgcgg 300

gcggggttct tgcgggctgc ccttctgggc tcccggaatg ttctnngaac ttgctgg 357

299

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgggaaac tccgaggaca 180

gagggctaaa tccatgaagt ttgtggatgg cctgatgatc cacagcggag accctgttaa 240

ctactacgtt gacacttgct tgtgcgccac gtgttgctca nacangggtg ggctgggcat 300

caaggng 307

300

351

Homo sapien

300

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacag caagtgtcaa cgtaagtaag ttaacagggt ctccgctgtg 300

gatcatcagg ccatccacaa acttcatgga tttaaccctc tgtcctcgga g 351

301

330

Homo sapien

301

tcgagcggcc gcccgggcag gtgtttcaga ggttccaagg tccactgtgg aggtcccagg 60

agtgctggtg gtgggcacag aggtccgatg ggtgaaacca ttgacataga gactgttcct 120

gtccagggtg taggggccca gctctttgat gccattggcc agttggctca gctcccagta 180

cagccgctct ctgttgagtc cagggctttt ggggtcaaga tgatggatgc agatggcatc 240

cactccagtg gctgctccat ccttctcgga cctgagagag gtcagtctgc agccagagta 300

cagagggcca acactggtgt tctttgaata 330

302

agcgtggtcg cggccgaggt ctgtactggg agctaagcaa actgaccaat gacattgaag 60

agctgggccc ctacaccctg gacaggaaca gtctctatgt caatggtttc acccatcaga 120

gctctgtgnc caccaccagc actcctggga cctccacagt ggatttcaga acctcaggga 180

ctccatcctc cctctccagc cccacaatta tggctgctgg ccctctcctg gtaccattca 240

ccctcaactt caccatcacc aacctgcagt atggggagga catgggtcac cctgnctcca 300

ggaagttcaa caccaca 317

303

tcgagcggcc gcccggacag gtctgggcgg atagcaccgg gcatattttg gaatggatga 60

ggtctggcac cctgagcagt ccagcgagga cttggtctta gttgagcaat ttggctagga 120

ggatagtatg cagcacggnt ctgagnctgt gggatagctg ccatgaagta acctgaagga 180

ggtgctggct ggtangggtt gattacaggg ttgggaacag ctcgtacact tgccattctc 240

tgcatatact ggttagtgag gtgagcctgg ccctcttctt ttg 283

304

agcgtggtcg cggccgaggt gagccacagg tgaccggggc tgaagctggg gctgctggnc 60

ctgctggtcc tg 72

305

cagcngctcc nacggggcct gngggaccaa caacaccgtt ttcaccctta ggccctttgg 60

ctcctctttc tcctttagca ccaggttgac cagcagcncc ancaggacca gcaaatccat 120

tggggccagc aggaccgacc tcaccacgtt caccagggct tccccgagga ccagcaggac 180

cagcaggacc agcagcccca gcttcgcccc ggtcacctgt ggctcacctc ggccgcgacc 240

acgct 245

306

tcgagcggtc gcccgggcag gtccaccggg atagccgggg gtctggcagg aatgggaggc 60

atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac 120

agagtgagga gcctggagac cganaaccgg aggctggana gcaaaatccg ggagcacttg 180

gagaagaagg gaccccaggt caagagactg gagccattac ttcaagatca tcgagggacc 240

tggagg 246

307

agcgnggtcg cggccgaggt ccagctctgt ctcatacttg actctaaagt catcagcagc 60

aagacgggca ttgtcaatct gcagaacgat gcgggcattg tccgcagtat ttgcgaagat 120

ctgagccctc aggtcctcga tgatcttgaa gtaatggctc cagtctctga cctggggtcc 180

cttcttctcc aagtgctccc ggattttgct ctccagcctc cggttctcgg tctccaggct 240

cctcactctg tccaggtaag aaggcccagg cggtcgttca ggctttgcat ggtctccttc 300

tcgttctgga tgcctcccat tcctgccaga ccc 333

308

310

Homo sapien

308

tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga 60

ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca 120

gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt 180

acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctct 240

tccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg 300

ttggtgatgg 310

309

429

Homo sapien

309

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacaccg caggtctcac 180

cagtctccat gttgcagaag actttgatgg catccaggtt gcagccttgg ttggggtcaa 240

tccagtactc tccactcttc cagtcagaag tgggcacatc ttgaggtcac cggcaggtgc 300

cgggccgggg gttcttgcgg cttgccctct gggctccgga tgttctcgat ctgcttggct 360

caggctcttg agggtgggtg tccacctcga ggtcacggtc accgaaacct gcccgggcgg 420

cccgctcga 429

310

tcgagcggtc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag 60

agcctgagcc agcagatcga gaacatccgg agcccagagg gcagccgcaa gaaccccgcc 120

cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt 180

gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt 240

gagacctgcg tgtaccccac tcagcccagt gtgggcccag aagaaactgg tacatcagca 300

aggaacccca aggacaagag gcattgtctt ggttcggcga gnagcatgac ccgatggatt 360

ccagtttcga gtattggcgg ccagggcttc ccgacccttg ccgatgtgga cctcggccgc 420

gaccaccgct 430

311

2996

Homo sapien

311

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180

ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240

ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300

tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360

cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420

tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480

gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540

tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600

gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660

gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720

gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780

gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840

ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900

accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960

cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag 1020

ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc 1080

aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag 1140

ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc 1200

ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc 1260

cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg 1320

aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc 1380

ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc 1440

cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct 1500

ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca 1560

gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc 1620

aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg 1680

gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg 1740

ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc 1800

acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg 1860

gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat 1920

agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata 1980

aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc 2040

accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat 2100

gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc 2160

aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag 2220

accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg 2280

acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac 2340

ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc 2400

aattaccaga ggaacaaaag gaatattgag gatgcgctca accaactctt ccgaaacagc 2460

agcatcaaga gttatttttc tgactgtcaa gtttcaacat tcaggtctgt ccccaacagg 2520

caccacaccg gggtggactc cctgtgtaac ttctcgccac tggctcggag agtagacaga 2580

gttgccatct atgaggaatt tctgcggatg acccggaatg gtacccagct gcagaacttc 2640

accctggaca ggagcagtgt ccttgtggat gggtattttc ccaacagaaa tgagccctta 2700

actgggaatt ctgaccttcc cttctgggct gtcatcctca tcggcttggc aggactcctg 2760

ggactcatca catgcctgat ctgcggtgtc ctggtgacca cccgccggcg gaagaaggaa 2820

ggagaataca acgtccagca acagtgccca ggctactacc agtcacacct agacctggag 2880

gatctgcaat gactggaact tgccggtgcc tggggtgcct ttcccccagc cagggtccaa 2940

agaagcttgg ctggggcaga aataaaccat attggtcgga cacaaaaaaa aaaaaa 2996

312

914

Homo sapien

312

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser

65 70 75 80

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

85 90 95

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala

100 105 110

Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

115 120 125

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu

130 135 140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr

145 150 155 160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val

165 170 175

Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala

180 185 190

Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn

195 200 205

Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr

210 215 220

Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr

225 230 235 240

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

245 250 255

Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

260 265 270

Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

275 280 285

Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu

290 295 300

Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val

305 310 315 320

Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn

325 330 335

Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly

340 345 350

Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser

355 360 365

Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg

370 375 380

Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp

385 390 395 400

Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile

405 410 415

Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg

420 425 430

Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

435 440 445

Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr

450 455 460

Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His

465 470 475 480

Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser

485 490 495

Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val

500 505 510

Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro

515 520 525

Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly

530 535 540

Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val

545 550 555 560

Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu

565 570 575

Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser

580 585 590

Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu

595 600 605

Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp

610 615 620

Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys

625 630 635 640

Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe

645 650 655

Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys

660 665 670

Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe

675 680 685

Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr

690 695 700

Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln

705 710 715 720

Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile

725 730 735

Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn

740 745 750

Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe

755 760 765

Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr

770 775 780

Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys

785 790 795 800

Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu

805 810 815

Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr

820 825 830

Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe Pro Asn Arg Asn

835 840 845

Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Leu

850 855 860

Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly

865 870 875 880

Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val

885 890 895

Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp

900 905 910

Leu Gln

313

656

Homo sapiens

313

acagccagtc ggagctgcaa gtgttctggg tggatcgcgy atatgcactc aaaatgctct 60

ttgtaaagga aagccacaac atgtccaagg gacctgaggc gacttggagg ctgagcaaag 120

tgcagtttgt ctacgactcc tcggagaaaa cccacttcaa agacgcagtc agtgctggga 180

agcacacagc caactcgcac cacctctctg ccttggtcac ccccgctggg aagtcctatg 240

agtgtcaagc tcaacaaacc atttcactgg cctctagtga tccgcagaag acggtcacca 300

tgatcctgtc tgcggtccac atccaacctt ttgacattat ctcagatttt gtcttcagtg 360

aagagcataa atgcccagtg gatgagcggg agcaactgga agaaaccttg cccctgattt 420

tggggctcat cttgggcctc gtcatcatgg taacactcgc gatttaccac gtccaccaca 480

aaatgactgc caaccaggtg cagatccctc gggacagatc ccagtataag cacatgggct 540

agaggccgtt aggcaggcac cccctattcc tgctccccca actggatcag gtagaacaac 600

aaaagcactt ttccatcttg tacacgagat acaccaacat agctacaatc aaacag 656

314

519

Homo sapiens

314

tgtgcgtgga ccagtcagct tccgggtgtg actggagcag ggcttgtcgt cttcttcaga 60

gtcactttgc aggggttggt gaagctgctc ccatccatgt acagctccca gtctactgat 120

gtttaaggat ggtctcggtg gttaggccca ctagaataaa ctgagtccaa tacctctaca 180

cagttatgtt taactgggct ctctgacacc gggaggaagg tggcggggtt taggtgttgc 240

aaacttcaat ggttatgcgg ggatgttcac agagcaagct ttggtatcta gctagtctag 300

cattcattag ctaatggtgt cctttggtat ttattaaaat caccacagca tagggggact 360

ttatgtttag gttttgtcta agagttagct tatctgcttc ttgtgctaac agggctattg 420

ctaccaggga ctttggacat gggggccagc gtttggaaac ctcatctagt ttttttgaga 480

gataggccac tggccttgga cctcggccgc gaccacgct 519

315

441

Homo sapiens

315

cacagagcgt ttattgacac caccactcct gaaaattggg atttcttatt aggttcccct 60

aaaagttccc atgttgatta catgtaaata gtcacatata tacaatgaag gcagtttctt 120

cagaggcaac cagggtttat agtgctaggt aaatgtcatc tcttttgtgc tactgactca 180

ttgtcaaacg tctctgcact gttttcagcc tctccacgtt gcctctgtcc tgcttcttag 240

ttccttcttt gtgacaaacc aaaagaataa gaggatttag aacaggactg cttttcccct 300

atgatttaaa aattccaatg actttcgccc ttgggagaaa tttccaagga aatctctctc 360

gctcgctctc tccgttttcc tttgtgagct tctgggggag ggttagtggt gactttttga 420

tacgaaaaaa tgcattttgt g 441

316

247

Homo sapiens

316

tggcgcggct gctggatttc accttcttgc acctgccggt gagcgcctgg ggtctaaagg 60

ggcgggatac tccattatgg cccctcgccc tgtagggctg gaatagttag aaaaggcaac 120

ccagtctagc ttggtaagaa gagagacatg cccccaacct cggcgccctt tttcctcacg 180

atctgctgtc cttacttcag cgactgcagg agcttcacct gcaagaaaac agcattgagc 240

tgctgac 247

317

409

Homo sapiens

317

tgacagggct cctggagttg ttaagtcacc aagtagctgc aggggatgga cactgcccca 60

cacgatgtgg gatgaacagc agccttggtt tgtagcccag ggtgtccatg gatttgaccc 120

gaatgctccc tggaggccct gtggcgagga caggcactgg atggtccaga ccctctggct 180

ggaggagtgg tggagccagg actgggcctt cagccatgag ggctagaata acctgacctc 240

ttgcattcta acactgggtc attaatgaca cctttccagt ggatgttgca aaaaccaaca 300

ctgtcaggaa cctggccctg ggagggctca ggtgagctca caaggagagg tcaagccaag 360

ccaaagggta ggkaacacac aacaccaggg gaaaccagcc cccaaacca 409

318

caaggnagat cttaagnggg gtcntatgta agtgtgctcc tggctccagg gttcctggag 60

cctcacgagg tcaggggaac ccttgtagaa ctccaccagc agcatcatct cgtgaaggat 120

gtcattggtc aggaagctgt cctggacgta ggccatctcc acatccatgg ggatgccata 180

gtcactgggc ctttgctcgg gaggaggcat cacccagaaa ggcgagatct tggactcggg 240

gcctgggttg ccagaatagt aaggggagca nagcagggcg aggcagggct ggaagccatt 300

gctggagccc tgcagccgca 320

319

tgaagcaata gcgcccccat tttacaggcg gagcatggaa gccagagagg tgggtggggg 60

agggggtcct tccctggctc aggcagatgg gaagatgagg aagccgctga agacgctgtc 120

ggcctcagag ccctggtaaa tgtgaccctt tttggggtct ttttcaaccc anacctggtc 180

accctgctgc agacctcggc cgcgaccacg ct 212

320

769

Homo sapiens

320

tggaggtgta gcagtgagag gagatytcag gcaagagtgt cacagcagag ccctaaascc 60

tccaactcac cagtgagaga tgagactgcc cagtactcag ccttcatctc ctgggccacc 120

tggagggcgt ctttctccat cagcgcatac tgagcagggg tactcagatc cttcttggaa 180

cctacaagga agagaagcac actggaaggg tcattctcct tcagggcatc ggccagccac 240

tgcctgccat gggaggtgga aagtaaggga tgagtgagtc tgcagggccc ctcccactga 300

cattcatagg cccaattacc ccctctctgg tcctacatgc attcttcttc ttcctgacca 360

cccctctgtt ctgaaccctc tcttcccgga gcctcccatt atattgcagg atgctcactt 420

acttggtatg ttccagagat gccacatcat tcaggttgaa gacaatgatg atggcttgga 480

agagtggcag aaacagcccc aggttgacag ggaagacact actgctcatt tccccaatcc 540

ttccagctcc atatgagaaa gccatgtgca ctctgagacc cacctacccc acttcaccca 600

gccccttacc ttgagctcct ctatagtagg ttgatgcaat gcatttgaac ctctcctgcc 660

cagcggtatc ccaactggaa ggaaggaaga gtgaagcaca ggtatgtatc ttggggggtg 720

tgggtgctgg ggagaaggga tagctggaag gggtgtggaa gcactcaca 769

321

tgggctgtgg gcggcacctg tgctctgcag gccagacagc gatagaagcc tttgtctgtg 60

cctactcccc cggaggcaac tgggaggtca acgggaagac aatcatcccc tataagaagg 120

gtgcctggtg ttcgctctgc acagccagtg tctcaggctg cttcaaagcc tgggaccatg 180

caggggggct ctgtgaggtc cccaggaatc cttgtcgcat gagctgccag aaccatggac 240

gtctcaacat cagcacctgc cactgccact gtccccctgg ctacacgggc agatactgcc 300

aagtgaggtg cagcctgcag tgtgtgcacg gccggttccg ggaggaggag tgctcgtgcg 360

tctgtgacat cggctacggg ggagcccagt gtgccaccaa ggtgcatttt cccttccaca 420

cctgtgacct gaggatcgac ggagactgct tcatggtgtc ttcagaggca gacacctatt 480

acagaagcca ggatgaaatg tcagaggaat ggcggggtgc tggcccagat caagagccag 540

aaagtgcagg acatcctcgc cttctatctg ggccgcctgg agaccaccaa cgaggtgact 600

gacagtgact ttgagaccag gaacttctgg atngggctca cctacaagac cgccaaggac 660

tccttncgct gggccacagg ggagcaccag 690

322

104

Homo sapiens

322

gtcgcaagcc ggagcaccac catgtagcct ttcccgaagt accggacctt ctcctcctcc 60

acgctcacat cacggacatc atggagcagg accaccacct ggtc 104

323

118

Homo sapiens

323

gggccctggg cgcttccaaa tgacccagga ggtggtctgc gacgaatgcc ctaatgtcaa 60

actagtgaat gaagaacgaa cactggaagt agaaatagag cctggggtga gagacgga 118

324

354

Homo sapiens

324

tgctctccgg gagcttgaag aagaaactgg ctacaaaggg gacattgccg aatgttctcc 60

agcggtctgt atggacccag gcttgtcaaa ctgtactata cacatcgtga cagtcaccat 120

taacggagat gatgccgaaa acgcaaggcc gaagccaaag ccaggggatg gagagtttgt 180

ggaagtcatt tctttaccca agaatgacct gctgcagaga cttgatgctc tggtagctga 240

agaacatctc acagtggacg ccagggtcta ttcctacgct ctagcgctga aacatgcaaa 300

tgcaaagcca tttgaagtgc ccttcttgaa attttaagcc caaatatgac actg 354

325

ncatgcttga atgggctcct ggtgagagat tgccccctgg tggtgaaaca atcgtgtgtg 60

cccactgata ccaagaccaa tgaaagagac acagttaagc agcaatccat ctcatttcca 120

ggcacttcaa taggtcgctg attggtcctt gcaccagcag tggtagtcgt acctatttca 180

gagaggtctg aaattcaggt tcttagtttg ccagggacag gccctacctt atattttttt 240

ccatcttcat catccacttc tgcttacagt ttgctgctta caataactta atgatggatt 300

gagttatctg ggtggtctct agccatctgg gcagtgtggt tctgtctaac caaagggcat 360

tggcctcaaa ccctgcattt ggtttagggg ctaacagagc tcctcagata atcttcacac 420

acatgtaact gctggagatc ttattctatt atgaataaga aacgagaagt ttttccaaag 480

tgttagtcag gatctgaagg ctgtcattca gataacccag cttttccttt tggcttttag 540

cccattcaga ctttgccaga gtcaagccaa ggattgcttt tttgctacag ttttctgcca 600

aatggcctag ttcctgagta cctggaaacc agagagaaag ag 642

326

455

Homo sapiens

326

tccgtgagga tgagcttcga gtccttcacc aggcactgca ggggcacagt cacgtcaatc 60

accttcacct tctcgctctt cctgctcttg tcattgacaa acttcccgta ccaggcattg 120

acgatgatga ggcccattct ggactcttct gcctcaatta tccttcggac agattcctgc 180

atcagccgga cagcggactc cgcctcttgc ttcttctgca gcacatcggt ggcggcgctt 240

tccctctgct tctccaattc cttctctttc tgagccctga ggtatggttt gatgatcaga 300

cggtgcatgg caaagtagac cactagaggc cccacggtgg catagaacat ggcgctgggc 360

agaagctggt ccgtcaagtg aatagggaag aagtatgtct gactggccct gttgagcttg 420

actttgagag aaacgccctg tggaactcca acgct 455

327

321

Homo sapiens

327

ttcactgtga actcgcagtc ctcgatgaac tcgcacagat gtgacagccc tgtctccttg 60

ctctctgagt tctcttcaat gatgctgatg atgcagtcca cgatagcgcg cttatactca 120

aagccaccct cttcccgcag catggtgaac aggaagttca taaggacggc gtgtttgcga 180

ggatatttct gacacagggc actgatggcc tggacaacca ccaccttgaa ttcatccgag 240

atttctgaca tgaaggagga gatctgcttc atgaggcggt cgatgctgct ctcgctgccc 300

gtcttaagga gggtggtgat g 321

328

tgcaggaggg gccatggggg ctgtgaatgg gatgcagccc catggtgtcc ctgataaatc 60

cagtgtgcag tctgatgaag tctgggtggg tgtggtctac gggctggcag ctaccatgat 120

ccaagaggta atgcactcct tttcccatct ctccaccatc tgtatcctgg ccmagaaaaa 180

cttcccttca aaccaaccaa aatttccttt caaaggcata acccaaatgc catccttggt 240

ccggtctaat aaagcctccc ccatttttcc cctggtatgc attcccaggc tccctggcct 300

tncagggctt nctgtctgtg ggtcatagtt tatctcctcc cacttgctgg gagctccttg 360

aaggcaaaga ctctactgcc tccatctatc cagtggaagt ggctcttcag agggtgccaa 420

gttagtatgt atgactgtca tctctcccaa cagggcctga cttggsaggg cttcca 476

329

340

Homo sapiens

329

cgagggagat tgccagcacc ctgatggaga gtgagatgat ggagatcttg tcagtgctag 60

ctaagggtga ccacagccct gtcacaaggg ctgctgcagc ctgcctggac aaagcagtgg 120

aatatgggct tatccaaccc aaccaagatg gagagtgagg gggttgtccc tgggcccaag 180

gctcatgcac acgctaccta ttgtggcacg gagagtaagg acggaagcag ctttggctgg 240

tggtggctgg catgcccaat actcttgccc atcctcgctt gctgccctag gatgtcctct 300

gttctgagtc agcggccacg ttcagtcaca cagccctgct 340

330

277

Homo sapiens

330

tgtcaccatc acattggtgc caaataccca gaagacatcg tagatgaaga gtccgcccag 60

caggatgcag ccagtgctga cattgttgag gtgcaggagc tctactccat taagggagaa 120

ggccaggcca aaaaggttgt tggcaatcca gtgcttcctc agcaggtacc agacgccaac 180

gatgctgctc aggcccaggc acaccaggtc cttggtgtca aattcataat tgatgatctc 240

ctccttgttt tcccagaacc ctgtgtgaag agcagac 277

331

136

Homo sapiens

331

ttgcttccca cctcctttct ctgtcctctc ctgaggttct gccttacaat ggggacactg 60

atacaaacca cacacacaat gaggatgaaa acagataaca ggtaaaatga cctcacctgc 120

ccgggcggcc gctcga 136

332

184

Homo sapiens

332

ttgtgagata aacgcagata ctgcaatgca ttaaaacgct tgaaatactc atcagggatg 60

ttgctgatct tattgttgtc taagtagaga gttagaagag agacagggag accagaaggc 120

agtctggcta tctgattgaa gctcaagtca aggtattcga gtgatttaag acctttaaaa 180

gcag 184

333

384

Homo sapiens

333

cggaaaactt cgaggaattg ctcaaagtgc tgggggtgaa tgtgatgctg aggaagattg 60

ctgtggctgc agcgtccaag ccagcagtgg agatcaaaca ggagggagac actttctaca 120

tcaaaacctc caccaccgtg cgcaccacag agattaactt caaggttggg gaggagtttg 180

aggagcagac tgtggatggg aggccctgta agagcctggt gaaatgggag agtgagaata 240

aaatggtctg tgagcagaag ctcctgaagg gagagggccc caagacctcg tggaccagag 300

aactgaccaa cgatggggaa ctgatcctga ccatgacggc ggatgacgtt gtgtgcacca 360

gggtctacgt ccgagagtga gcgg 384

334

cnacaaacag agcagacacc ctggatccgg tcctgctact ggccaggacg gctggaccgt 60

aaaattgaat ttccacttcc tgaccgccgc cagaagagat tgattttctc cactatcact 120

agcaagatga acctctctga ggaggttgac ttggaagact atgtngccc 169

335

185

Homo sapiens

335

ccaggtttgc agcccaggct gcacatcagg ggactgcctc gcaatacttc atgctgttgc 60

tgctgactga tggtgctgtg acggatgtgg aagccacacg tgaggctgtg gtgcgtgcct 120

cgaacctgcc catgtcagtg atcattgtgg gtgtgggtgg tgctgacttt gaggccatgg 180

agcag 185

336

ctgcccctgc cttacggcgg ccaganacac acccaggatg gcattggccc caaacttgga 60

tttgttctca gtcccatcca actccagcat caggttgtcc agtttctctt gctccaccac 120

agagagacct gagctgatga gggctggcgc gatggtggag ttgatgtggt ccactgcctt 180

caggacacct ttgcctaagt aacgctgttt gtctccatcc ctcagctcca gggcctcata 240

gatgcccgta gaggctccac tgggcactgc agcccggaaa agacctttgg cagtatagag 300

atccacctcc actgtggggt tcccgcggga gtccaggatc tcccgggccc agatcttc 358

337

cacaaagcca ccagccnggg aaatcagaat ttacttgatg caactgactt gtaatagcca 60

gaaatcctgc ccagcatggg attcagaacc tggtctgcaa ccaaatccac cgtcaaagtt 120

catacaggat aaaacaaatt caattgcctt ttccacatta atagcatcaa gcttccccaa 180

caaagccaaa gttgccaccg cacaaaaaga gaatcttgtg tcaatttctc cctactttat 240

aaaagtagat ttttcacatc ccatgaagca g 271

338

ctgtgctccc gactngnnca tctcaggtac caccgactgc actgggcggg gccctctggg 60

gggaaaggct ccacggggca gggatacatc tcgaggccag tcatcctctg gaggcagccc 120

aatcaggtca aagattttgc ccaactggtc ggcttcagag tttccacaga agagaggctt 180

tcgacgaaac atctctgcaa agatacagcc aacactccac atgtccacag gtgttgcata 240

tgtggactgc agaagaactt cgggagctcg gtaccagagt gtaacaacca cgggtgtaag 300

tgccatctgg tagctgtaga ttctgg 326

339

ttcacctgag gactcatttc gtgccctttg ttgacttcaa gcaaagncct tcanggtctn 60

caaggacgnc acatttccac ttgcgaatgn nctcanggct catcttgaag aanaagnanc 120

ccaagtgctg gatcccagac tcgggggtaa ccttgtgggt aagagctcat ccagtttatg 180

ctttaggacg tccanctact cgggggagct ggaagcctgc gtggatgcgg ccctgctgga 240

cctcggccgc gaccacgcta 260

340

ctggaagccc ggctnggnct ggcagcggaa ggagccaggc aggttcacgc agcggtgctg 60

gcagtagcgg tagcggcact cgtctatgtc cacacactcg ggcccgatct tgcggtaacc 120

atcagggcag gtgcactgat aggagccagg caagttatgg cagtcctggc tggggcgaca 180

gtcgtgcagg gcctgggcac actcgtccac atccacacag 220

341

384

Homo sapiens

341

ctgctaccag gggagcgaga gctgactatc ccagcctcgg ctaatgtatt ctacgccatg 60

gatggagctt cacacgattt cctcctgcgg cagcggcgaa ggtcctctac tgctacaccg 120

ggcgtcacca gtggcccgtc tgcctcagga actcctccga gtgagggagg agggggctcc 180

tttcccagga tcaaggccac agggaggaag attgcacggg cactgttctg aggaggaagc 240

cccgttggct tacagaagtc atggtgttca taccagatgt gggtagccat cctgaatggt 300

ggcaattata tcacattgag acagaaattc agaaagggag ccagccaccc tggggcagtg 360

aagtgccact ggtttaccag acag 384

342

245

Homo sapiens

342

ctggctaagc tcatcattgt tactggtggg caccatgtcc ttgaagcttc aggcaagcaa 60

tgtaaccaac aagaatgacc ccaagtccat caactctcga gtcttcattg gaaacctcaa 120

cacagctctg gtgaagaaat cagatgtgga gaccatcttc tctaagtatg gccgtgtggc 180

cggctgttct gtgcacaagg gctatgcctt tgttcagtac tccaatgagc gccatgcccg 240

ggcag 245

343

611

Homo sapiens

343

ccaaaaaaat caagatttaa tttttttatt tgcactgaaa aactaatcat aactgttaat 60

tctcagccat ctttgaagct tgaaagaaga gtctttggta ttttgtaaac gttagcagac 120

tttcctgcca gtgtcagaaa atcctattta tgaatcctgt cggtattcct tggtatctga 180

aaaaaatacc aaatagtacc atacatgagt tatttctaag tttgaaaaat aaaaagaaat 240

tgcatcacac taattacaaa atacaagttc tggaaaaaat atttttcttc attttaaaac 300

tttttttaac taataatggc tttgaaagaa gaggcttaat ttgggggtgg taactaaaat 360

caaaagaaat gattgacttg agggtctctg tttggtaaga atacatcatt agcttaaata 420

agcagcagaa ggttagtttt aattatgtag cttctgttaa tattaagtgt tttttgtctg 480

ttttacctca atttgaacag ataagtttgc ctgcatgctg gacatgcctc agaaccatga 540

atagcccgta ctagatcttg ggaacatgga tcttagagtc ctttggaata agttcttata 600

taaatacccc c 611

344

nctcgaaaaa gcccaagaca gcagaagcag acacctccag tgaactagca aagaaaagca 60

aagaagtatt cagaaaagag atgtcccagt tcatcgtcca gtgcctgaac ccttaccgga 120

aacctgactg caaagtggga agaattacca caactgaaga ctttaaacat ctggctcgca 180

agctgactca cggtgttatg aataaggagc tgaagtactg taagaatcct gaggacctgg 240

agtgcaatga gaatgtgaaa cacaaaacca aggantacat taanaagtac atgcannaan 300

tttggggctt g 311

345

201

Homo sapiens

345

cacacggtca tcccgactgc caacctggag gcccaggccc tgtggaagga gccgggcagc 60

aatgtcacca tgagtgtgga tgctgagtgt gtgcccatgg tcagggacct tctcaggtac 120

ttctactccc gaaggattga catcaccctg tcgtcagtca agtgcttcca caagctggcc 180

tctgcctatg gggccaggca g 201

346

370

Homo sapiens

346

ctgctccagg gcgtggtgtg ccttcgtggc ctctgcctcc tccgaggagc caggctgtgt 60

tctcttcaga atgttctgga gcagcagttt gaggcgggtg atgcgttgga agggcagaat 120

cagaaaggac ttgagggaaa ggcgctggca gacggggtcg ctctccagct tctccaagac 180

ctcccggaaa ttgctgttgc tattcatcag gctctggaag gtgcgttcct gataggtctg 240

gttggtgaca taaggcaggt agacccggcg gaagtctggg gcgtggttca ggactacgtc 300

acatacttgg aaggagaaga tattgttctc aaagttctct tccaggtctg aaaggaacgt 360

ggcgctgacg 370

347

ctgttgtgct gtgtatggac gtgggcttta ccatgagtaa ctccattcct ggtatagaat 60

ccccatttga acaagcaaag aaggtgataa ccatgtttgt acagcgacag gtgtttgctg 120

agaacaagga tgagattgct ttagtcctgt ttggtacaga tggcactgac aatccccttt 180

ctggtgggga tcagtatcag aacatcacag tgcacagaca tctgatgcta ccagattttg 240

atttgctgga ggacattgaa agcaaaatcc aaccaggttc tcaacaggct gacttcctgg 300

atgcactaat cgtgagcatg gatgtgattc aacatgaaac aataggaaag aagtttggag 360

aagaggcata ttgaaatatt cactgacctc aagcagcccg attcagcaaa agtcan 416

348

351

Homo sapiens

348

gtacaggaga ggatggcagg tgcagagcgg gcactgagct ctgcaggtga aagggctcgg 60

cagttggatg ctctcctgga ggctctgaaa ttgaaacggg caggaaatag tctggcagcc 120

tctacagcag aagaaacggc aggcagtgcc cagggacgag caggagacag atgccttcct 180

cttgtctcaa ctgcaaagag gcgttccttc ctctttcact aatcctcctc agcacagacc 240

ctttacgggt gtcaggctgg gggacagtaa ggtctttccc ttcccacaag gccatatctc 300

aggctgtctc agtgggggga aaccttggac aatacccggg ctttcttggg c 351

349

nccgggacat ctccaccctc aacagtggca agaagagcct ggagactgaa cacaaggcct 60

tgaccagtga gattgcactg ctgcagtcca ggctgaagac agagggctct gatctgtgcg 120

acagagtgag cgaaatgcag aagctggatg cacaggtcaa ggagctggtg ctgaagtcgg 180

cggtggaggc tgagcgcctg gtggctg 207

350

323

Homo sapiens

350

ccatacaggg ctgttgccca ggccctagag gtcattcctc gtaccctgat ccagaactgt 60

ggggccagca ccatccgtct acttacctcc cttcgggcca agcacaccca ggagaactgt 120

gagacctggg gtgtaaatgg tgagacgggt actttggtgg acatgaagga actgggcata 180

tgggagccat tggctgtgaa gctgcagact tataagacag cagtggagac ggcagttctg 240

ctactgcgaa ttgatgacat cgtttcaggc cacgaaaaga aaggcgatga ccagagccgg 300

caaggcgggg ctcctgatgc tgg 323

351

cgccgcatcc cntggtccct tccantccct tttcctttnt cngggaacgt gtatgcggtt 60

tgtttttgtt ttgtagggtt tttttccttc tccacctctc cctgtctctt ttgctccatg 120

ttgtccgttt ctgtggggtt aggtttatgt ttttaatcat ctgaggtcac gtctatttcc 180

tccggactcg cctgcttggt ggcgattctc caccggttaa tatggtgcgt cccttttttc 240

ttttgttgcg aatctgagcc ttcttcctcc agcttctgcc ttttgaactt tgttcttcgg 300

ttctgaaacc atacttttac ctgagtttcc gtgaggctga ggctgtgtgc caa 353

352

467

Homo sapiens

352

ctgcccacac tgatcacttg cgagatgtcc ttagggtaca agaacaggaa ttgaagtctg 60

aatttgagca gaacctgtct gagaaactct ctgaacaaga attacaattt cgtcgtctca 120

gtcaagagca agttgacaac tttactctgg atataaatac tgcctatgcc agactcagag 180

gaatcgaaca ggctgttcag agccatgcag ttgctgaaga ggaagccaga aaagcccacc 240

aactctggct ttcagtggag gcattaaagt acagcatgaa gacctcatct gcagaaacac 300

ctactatccc gctgggtagt gcagttgagg ccatcaaagc caactgttct gataatgaat 360

tcacccaagc tttaaccgca gctatccctc cagagtccct gacccgtggg gtgtacagtg 420

aagagaccct tagagcccgt ttctatgctg ttcaaaaact ggcccga 467

353

350

Homo sapiens

353

ctgctgcagc cacagtagtt cctcccatgg tgggtggccc tcctggtcct gctggcccag 60

gaaatctgtc cccaccagga acagcccctg gaaaacggcc ccgtcctcta ccaccttgtg 120

gaaatgctgc acgggaactg cctcctggag gaccagcttt accttcccca gacatttgtc 180

ctgattgtgt agttttcctg gactgcattt caaattgact caggaactgt ttattgcatg 240

gagttacaac aggattctga ccatgaagtt ctcttttagg taacagatcc attaactttt 300

ttgaagatgc ttcagatcca acaccaacaa gggcaaaccc ctttgactgg 350

354

351

Homo sapiens

354

atttagatga gatctgaggc atggagacat ggagacagta tacagactcc tagatttaag 60

ttttaggttt tttgcttttc taatcaccaa ttcttatata caatgtatat tttagactcg 120

agcagatgat catcttcatc ttaagtcatt ccttttgact gagtatggca ggattagagg 180

gaatggcagt atagatcaat gtctttttct gtaaagtata ggaaaaacca gagaggaaaa 240

aaagagctga caattggaag gtagtagaaa attgacgata atttcttctt aacaaataat 300

agttgtatat acaaggaggc tagtcaacca gattttattt gttgagggcg a 351

355

308

Homo sapiens

355

ttttggcgca agttttacag attttattaa agtcgaagct attggtcttg gaagatgaaa 60

atgcaaatgt tgatgaggtg gaattgaagc cagatacctt aataaaatta tatcttggtt 120

ataaaaataa gaaattaagg gttaacatca atgtgccaat gaaaaccgaa cagaagcagg 180

aacaagaaac cacacacaaa aacatcgagg aagaccgcaa actactgatt caggcggcca 240

tcgtgagaat catgaagatg aggaaggttc tgaaacacca gcagttactt ggcgaggtcc 300

tcactcag 308

356

207

Homo sapiens

356

ctgtcccaag tgctcccaga aggcaggatt ctgaagacca ctccagcgat atgttcaact 60

atgaagaata ctgcaccgcc aacgcagtca ctgggccttg ccgtgcatcc ttcccacgct 120

ggtactttga cgtggagagg aactcctgca ataacttcat ctatggaggc tgccggggca 180

ataagaacag ctaccgctct gaggagg 207

357

tcgaccacgc cctcgtagcg catgngctnc aggacgatgc tcagagtgat gaacaccccg 60

gtgcggccca cgccagcact gcagtgcacc gtgataggcc catcctgtcc aaactgctcc 120

ttggtcttat gcacctgccc gatgaagtca atgaatccct cgcctgtctt gggcacgccc 180

tgctctgg 188

358

291

Homo sapiens

358

ctgggagcat cggcaagcta ctgccttaaa atccgatctc cccgagtgca caatttctgt 60

cccttttaag ggttcacaac actaaagatt tcacatgaaa gggttgtgat tgatttgagc 120

aggcaggcgg tacgtgacag gggctgcatg caccggtggt cagagagaaa cagaacaggg 180

cagggaattt cacaatgttc ttctatacaa tggctggaat ctatgaataa catcagtttc 240

taagttatgg gttgattttt aactactggg tttaggccag gcaggcccag g 291

359

gccaccacac tccagcctgg gcaatacagc aagactgtct caaaaaaaaa aaaaaaaaaa 60

cccaaaaaaa ctcaaaaang taatgaatga tacccaangn gccttttcta gaaaaag 117

360

394

Homo sapiens

360

ctgttcctct ggggtggtcc agttctagag tgggagaaag ggagtcaggc gcattgggaa 60

tcgtggttcc agtctggttg cagaatctgc acatttgcca agaaattttc cctgtttgga 120

aagtttgccc cagctttccc gggcacacca ccttttgtcc caagtgtctg ccggtcgacc 180

aatctgcctg ccacacattg accaagccag acccggttca cccagctcga ggatcccagg 240

ttgaagagtg gccccttgag gccctggaaa gaccaatcac tggacttctt cccttgagag 300

tcagaggtca cccgtgattc tgcctgcacc ttatcattga tctgcagtga tttctgcaaa 360

tcaagagaaa ctctgcaggg cactcccctg tttc 394

361

ctgggcggat agcaccgggc atattttntt natggatgag gtctggcacc ctgagcagtc 60

cagcgaggac ttggtcttag ttgagcaatt tggctaggag gatagtatgc agcacggttc 120

tgagtctgtg ggatagctgc catgaagtaa cctgaaggag gtgctggctg gtaggggttg 180

attacagggt tgggaacagc tcgtacactt gccattctct gcatatactg gttagtgagg 240

tgagcctggc gctcttcttt gcgctgagct aaagctacat acaatggctt tgtggacctc 300

ggccgcgacc acgctaagcc gaattccagc acactggcgg ccgttactag tggatccgag 360

ctcggtacca agcttggcgt aatcatggtc atag 394

362

268

Homo sapiens

362

ctgcgcgtgg accagtcagc ttccgggtgt gactggagca gggcttgtcg tcttcttcag 60

agtcactttg caggggttgg tgaagctgct cccatccatg tacagctccc agtctactga 120

tgtttaagga tggtctcggt ggttaggccc actagaataa actgagtcca atacctctac 180

acagttatgt ttaactgggc tctctgacac cgggaggaag gtggcggggt ttaggtgttg 240

caaacttcaa tggttatgcg gggatgtt 268

363

323

Homo sapiens

363

ccttgacctt ttcagcaagt gggaaggtgt aatccgtctc cacagacaag gccaggactc 60

gtttgtaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca 120

gacagacact ggcaacattg cggacaccct ccaggaagcg agaatgcaga gtttcctctg 180

tgatatcaag cacttcaggg ttgtagatgc tgccattgtc gaacacctgc tggatgacca 240

gcccaaagga gaagggggag atgttgagca tgttcagcag cgtggcttcg ctggctccca 300

ctttgtctcc agtcttgatc aga 323

364

ccaagctctc catcgtcccc gtgcgcagng gctactgggg gaacaagatc ggcaagcccc 60

acactgtccc ttgcaaggtg acaggccgct gcggctctgt gctggtacgc ctcatcactg 120

cacccagggg cactggcatc gtctccgcac ctgtgcctaa gaagctgctc atgatggctg 180

gcatcgatga ctgctacacc tcagcccggg gctgcactgc caccctgggc aacttcgcca 240

aggccacctt tgatgccatt tctaagacct acagctacct gacccccgac ctctggaagg 300

agactgtatt caccaagtct ccctatcagg agttcactga ccacctcgtc aagacccaca 360

ccagagtctc cgtgcagcgg actcaggctc cag 393

365

371

Homo sapiens

365

cctcctcaga gcggtagctg ttcttattgc cccggcagcc tccatagatg aagttattgc 60

aggagttcct ctccacgtca aagtaccagc gtgggaagga tgcacggcaa ggcccagtga 120

ctgcgttggc ggtgcagtat tcttcatagt tgaacatatc gctggagtgg tcttcagaat 180

cctgccttct gggagcactt gggacagagg aatccgctgc attcctgctg gtggacctcg 240

gccgcgacca cgctaagccg aattccagca cactggcggc cgttactagt ggatccgagc 300

tcggtaccaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg 360

ctcacaattc c 371

366

393

Homo sapiens

366

atttcttgcc agatgggagc tctttggtga agactccttt cgggaaaagt tttttggctt 60

cttcttcagg gatggttgga aggaccatca cactatcccc atccttccaa tcaactgggg 120

tggcaaccct tttttctgct gtcagctgga gagagatgac taccctgaga atctcatcaa 180

agttcctgcc agtggtagct gggtagagga tagacagctt cagcttctta tcaggaccaa 240

aaacaaacac cacacgagct gccacaggca tgcccttttc atccttctct gctggatcca 300

gcatgcccaa caggatggca agctcccgat tcctatcatc gatgatggga aaaggtaact 360

tttctgtggg ctcttcacaa ttgtaagcat tga 393

367

ccagctctgt ctcatacttg actctaaagt cttnagcagc aagacgggca ttgnnaatct 60

gcagaacgat gcgggcattg tccacagtat ttgcgaagat ctgagccctc aggtcctcga 120

tgatcttgaa gtaatggctc cagtctctga cctggggtcc cttcttctcc aagtgctccc 180

ggattttgct ctccagcctc cggttctcgg tctccaggct cctcactctg tccaggtaag 240

aggccaggcg gtcgttcagg ctttgcatgg tctccttctc gttctggatg cctcccattc 300

ctgccagacc cccggctatc ccggtgg 327

368

ctggagaagg acttcagcag tttnaagaag tactgccaag tcatccgtgt cattgcccac 60

acccagatgc gcctgcttcc tctgcgccag aagaaggccc acctgatgga gatccaggtg 120

aacggaggca ctgtggccga gaagctggac tgggcccgcg agaggcttga gcagcaggta 180

cctgtgaacc aagtgtttgg gcaggatgag atgatcgacg tcatcggggt gaccaagggc 240

aaaggctaca aaggggtcac cagtcgttgg cacaccaaga agctgccccg caagacccac 300

cgagga 306

369

394

Homo sapiens

369

tcgacccaca ccggaacacg gagagctggg ccagcattgg cacttgatag gatttcccgt 60

cggctgccac gaaagtgcgt ttctttgtgt tctcgggttg gaaccgtgat ttccacagac 120

ccttgaaata cactgcgttg acgaggacca gtctggtgag cacaccatca ataagatctg 180

gggacagcag attgtcaatc atatccctgg tttcattttt aacccatgca ttgatggaat 240

cacaggcaga ggctggatcc tcaaagttca cattccggac ctcacactgg aacacatctt 300

tgttccttgt aacaaaaggc acttcaattt cagaggcatt cttaacaaac acggcgttag 360

ccactgtcac aatgtcttta ttcttcttgg agac 394

370

653

Homo sapiens

370

ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg attaccggct 60

acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct cggccccgcc 120

ctggtgtcac agaggctact attactggcc tggaaccggg aaccgaatat acaatttatg 180

tcattgccct gaagaataat cagaagagcg agcccctgat tggaaggaaa aagacagacg 240

agcttcccca actggtaacc cttccacacc ccaatcttca tggaccagag atcttggatg 300

ttccttccac agttcaaaag acccctttcg tcacccaccc tgggtatgac actggaaatg 360

gtattcagct tcctggcact tctggtcagc aacccagtgt tgggcaacaa atgatctttg 420

aggaacatgg ttttaggcgg accacaccgc ccacaacggc cacccccata aggcataggc 480

caagaccata cccgccgaat gtaggacaag aagctctctc tcagacaacc atctcatggg 540

ccccattcca ggacacttct gagtacatca tttcatgtca tcctgttggc actgatgaag 600

aacccttaca gttcagggtt cctggaactt ctaccagtgc cactctgaca gga 653

371

268

Homo sapiens

371

ctgcccagcc cccattggcg agtttgagaa ggtgtgcagc aatgacaaca agaccttcga 60

ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa 120

gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct 180

gaccgaattc cccctgcgca tgcgggactg gctcaagaac gtcctggtca ccctgtatga 240

gagggatgag gacaacaacc ttctgact 268

372

392

Homo sapiens

372

gctggtgccc ctggtgaacg tggacctcct ggattggcag gggccccagg acttagaggt 60

ggaactggtc cccctggtcc cgaaggagga aagggtgctg ctggtcctcc tgggccacct 120

ggtgctgctg gtactcctgg tctgcaagga atgcctggag aaagaggagg tcttggaagt 180

cctggtccaa agggtgacaa gggtgaacca ggcggtccag gtgctgatgg tgtcccaggg 240

aaagatggcc caaggggtcc tactggtcct attggtcctc ctggcccagc tggccagcct 300

ggagataagg gtgaaggtgg tgcccccgga cttccaggta tagctggacc tcgtggtagc 360

cctggtgaga gaggtgaaac ctcggccgcg ac 392

373

ccaagcgctc agatcggcaa ggggcaccan ttttgatctg cccagtgcac agccccacaa 60

ccaggtcagc gatgaaggta tcttcagtct cccccgaacg atgagacacc atgacgcccc 120

aaccattggc ctgggccagc ttgcacgcct gaagagactc ggtcacggag ccaatctggt 180

tgactttgag caggaggcag ttgcaggact tctcgttcac ggccttggcg atcctctttg 240

ggttggtcac tgtgagatca tcccccacta cctggattcc tgcactggct gtgaacttct 300

gccaagctcc ccagtcatcc tggtcaaagg gatcttcgat agacaccact gggtagtcct 360

tgatgaagga cttgtacagg tcagccag 388

374

393

Homo sapiens

374

ctgacgaccg cgtgaacccc tgcattgggg gtgtcatcct cttccatgag acactctacc 60

agaaggcgga tgatgggcgt cccttccccc aagttatcaa atccaagggc ggtgttgtgg 120

gcatcaaggt agacaagggc gtggtccccc tggcagggac aaatggcgag actaccaccc 180

aagggttgga tgggctgtct gagcgctgtg cccagtacaa gaaggacgga gctgacttcg 240

ccaagtggcg ttgtgtgctg aagattgggg aacacacccc ctcagccctc gccatcatgg 300

aaaatgccaa tgttctggcc cgttatgcca gtatctgcca gcagaatggc attgtgccca 360

tcgtggagcc tgagatcctc cctgatgggg acc 393

375

ccacaaatgg cgtggtccat gtcatcaccn ttnttctgca gcctccagcc aacagacctc 60

aggaaagagg ggatgaactt gcagactctg cgcttgagat cttcaaacaa gcatcagcgt 120

tttccagggc ttcccagagg tctgtgcgac tagcccctgt ctatcaaaag ttattagaga 180

ggatgaagca ttagcttgaa gcactacagg aggaatgcac cacggcagct ctccgccaat 240

ttctctcaga tttccacaga gactgtttga atgttttcaa aaccaagtat cacactttaa 300

tgtacatggg ccgcaccata atgagatgtg agccttgtgc atgtggggga ggagggagag 360

agatgtactt tttaaatcat gttcccccta aaca 394

376

ctgcccagcc cccattggcg agtttgattn ggtgtgcagc aatgacaaca agaccttcga 60

ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa 120

gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct 180

gaccgaattc cccctgcgca tgcgggactg gctcaagaac gtcctggtca ccctgtatga 240

gagggatgag gacaacaacc ttctgactga gaagcagaag ctgcgggtga agaagatcca 300

tgagaatgag aagcgcctgg aggcaggaga ccaccccgtg gagctgctgg cccgggactt 360

cgagaagaac tataacatgt acatcttccc tg 392

377

292

Homo sapiens

377

caatgtttga tgcttaaccc ccccaatttc tgtgagatgg atggccagtg caagcgtgac 60

ttgaagtgtt gcatgggcat gtgtgggaaa tcctgcgttt cccctgtgaa agcttgattc 120

ctgccatatg gaggaggctc tggagtcctg ctctgtgtgg tccaggtcct ttccaccctg 180

agacttggct ccaccactga tatcctcctt tggggaaagg cttggcacac agcaggcttt 240

caagaagtgc cagttgatca atgaataaat aaacgagcct atttctcttt gc 292

378

395

Homo sapiens

378

ctgctgcttc agcgaagggt ttctggcata tccaatgata aggctgccaa agactgttcc 60

aataccagca ccagaaccag ccactcctac tgttgcagca cctgcaccaa taaatttggc 120

agcagtatca atgtctctgc tgattgcact ggtctgaaac tccctttgga ttagctgaga 180

cacaccattc tgggccctga ttttcctaag atagaactcc aactctttgc cctctagcac 240

atagccatct gctcggccac actgtcccgg ccttgaagcg atgcacgcaa gaagcttgcc 300

ctgctggaac tgctcctcca ggagactgct gattttggca ttctttttcc tttcatcata 360

tttcttctga attttttaga tcgttttttg tttaa 395

379

223

Homo sapiens

379

ccagatgaaa tgctgccgca atggctgtgg gaaggtgtcc tgtgtcactc ccaatttctg 60

agctccagcc accaccaggc tgagcagtga ggagagaaag tttctgcctg gccctgcatc 120

tggttccagc ccacctgccc tccccttttt cgggactctg tattccctct tgggctgacc 180

acagcttctc cctttcccaa ccaataaagt aaccactttc agc 223

380

tcgaccacag tattccaacc ctcctgtgcn tngagaagtg atggagggtg ctgacaacca 60

gggtgcagga gaacaaggta gaccagtgag gcagaatatg tatcggggat atagaccacg 120

attccgcagg ggccctcctc gccaaagaca gcctagagag gacggcaatg aagaagataa 180

agaaaatcaa ggagatgaga cccaaggtca gcagccacct caacgtcggt accgccgcaa 240

cttcaattac cgacgcagac gcccagaaaa ccctaaacca caagatggca aagagacaaa 300

agcagccgat ccaccag 317

381

cctgaaggaa gagctggcct acctgaatnn naaccatgag gaggaaatca gtacgctgag 60

gggccaagtg ggaggccagg tcagtgtgga ggtggattcc gctccgggca ccgatctcgc 120

caagatcctg agtgacatgc gaagccaata tgaggtcatg gccgagcaga accggaagga 180

tgctgaagcc tggttcacca gccggactga agaattgaac cgggaggtcg ctggccacac 240

ggagcagctc cagatgagca ggtccgaggt tactgacctg cggcgcaccc ttcagggtct 300

tgagattgag ctgcagtcac agacctcggc cgcgaccacg ctaagccgaa ttccagcaca 360

ctggcggccg ttactagtgg atccgagctc gg 392

382

234

Homo sapiens

382

cctcgatgtc taaatgagcg tggtaaagga tggtgcctgc tggggtctcg tagatacctc 60

gggacttcat tccaatgaag cggttctcca cgatgtcaat acggcccacg ccatgcttgc 120

ccgcgacttc gttcaggtac atgaagagct ccaaggaggt ctggtgggtg gtgccatcct 180

tgacgttggt caccttcaca gggacccctt ttttgaactc catctccaga atgt 234

383

ccttgacctt ttcagcaagt gggaaggtgt tttccgtctc cacagacaag gccaggactc 60

gtttgnaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca 120

gacagacact ggcaacattg cggacaccca ggatttcaat ggtgcccctg gagattttag 180

tggtgatacc taaagcctgg aaaaaggagg tcttctcggg cccgagacca gtgttctggg 240

ctggcacagt gacttcacat ggggcaatgg caccagcacg ggcagcagac ctgcccgggc 300

ggccgctcga aagccgaatt ccagcacact ggcggccgtt actagtggat ccgagctcgg 360

taccaagctt ggcgtaatca tggtcatagc tgtttc 396

384

396

Homo sapiens

384

gctgaatagg cacagagggc acctgtacac cttcagacca gtctgcaacc tcaggctgag 60

tagcagtgaa ctcaggagcg ggagcagtcc attcaccctg aaattcctcc ttggtcactg 120

ccttctcagc agcagcctgc tcttcttttt caatctcttc aggatctctg tagaagtaca 180

gatcaggcat gacctcccat gggtgttcac gggaaatggt gccacgcatg cgcagaactt 240

cccgagccag catccaccac atcaaaccca ctgagtgagc tcccttgttg ttgcatggga 300

tggcaatgtc cacatagcgc agaggagaat ctgtgttaca cagcgcaatg gtaggtaggt 360

taacataaga tgcctccgtg agaggctggt ggtcag 396

385

2943

Homo sapiens

385

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180

ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240

ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300

tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360

cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420

tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480

gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540

tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600

gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660

gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720

gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780

gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840

ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900

accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960

cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag 1020

ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc 1080

aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag 1140

ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc 1200

ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc 1260

cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg 1320

aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc 1380

ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc 1440

cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct 1500

ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca 1560

gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc 1620

aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg 1680

gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg 1740

ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc 1800

acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg 1860

gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat 1920

agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata 1980

aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc 2040

accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat 2100

gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc 2160

aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag 2220

accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg 2280

acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac 2340

ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc 2400

aattaccaga ggaacaaaag gaatattgag gatgcggcac cacaccgggg tggactccct 2460

gtgtaacttc tcgccactgg ctcggagagt agacagagtt gccatctatg aggaatttct 2520

gcggatgacc cggaatggta cccagctgca gaacttcacc ctggacagga gcagtgtcct 2580

tgtggatggg tattttccca acagaaatga gcccttaact gggaattctg accttccctt 2640

ctgggctgtc atcctcatcg gcttggcagg actcctggga ctcatcacat gcctgatctg 2700

cggtgtcctg gtgaccaccc gccggcggaa gaaggaagga gaatacaacg tccagcaaca 2760

gtgcccaggc tactaccagt cacacctaga cctggaggat ctgcaatgac tggaacttgc 2820

cggtgcctgg ggtgcctttc ccccagccag ggtccaaaga agcttggctg gggcagaaat 2880

aaaccatatt ggtcggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2940

aaa 2943

386

2608

Homo sapiens

386

gttcaagagc accagtgttg gccctctgta ctctggctgc agactgactt tgctcaggcc 60

tgaaaaggat gggacagcca ctggagtgga tgccatctgc acccaccacc ctgaccccaa 120

aagccctagg ctggacagag agcagctgta ttgggagctg agccagctga cccacaatat 180

cactgagctg ggcccctatg ccctggacaa cgacagcctc tttgtcaatg gtttcactca 240

tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc tgggagcatc 300

taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga tactattcac 360

cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg gctccaggaa 420

gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca agaacaccag 480

tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga aagatgggga 540

agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc ctgggctgga 600

cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg agctgggccc 660

ctacacactg gacagggaca gtctctatgt caatggtttc acccatcgga gctctgtacc 720

caccaccagc accggggtgg tcagcgagga gccattcaca ctgaacttca ccatcaacaa 780

cctgcgctac atggcggaca tgggccaacc cggctccctc aagttcaaca tcacagacaa 840

cgtcatgaag cacctgctca gtcctttgtt ccagaggagc agcctgggtg cacggtacac 900

aggctgcagg gtcatcgcac taaggtctgt gaagaacggt gctgagacac gggtggacct 960

cctctgcacc tacctgcagc ccctcagcgg cccaggtctg cctatcaagc aggtgttcca 1020

tgagctgagc cagcagaccc atggcatcac ccggctgggc ccctactctc tggacaaaga 1080

cagcctctac cttaacggtt acaatgaacc tggtccagat gagcctccta caactcccaa 1140

gccagccacc acattcctgc ctcctctgtc agaagccaca acagccatgg ggtaccacct 1200

gaagaccctc acactcaact tcaccatctc caatctccag tattcaccag atatgggcaa 1260

gggctcagct acattcaact ccaccgaggg ggtccttcag cacctgctca gacccttgtt 1320

ccagaagagc agcatgggcc ccttctactt gggttgccaa ctgatctccc tcaggcctga 1380

gaaggatggg gcagccactg gtgtggacac cacctgcacc taccaccctg accctgtggg 1440

ccccgggctg gacatacagc agctttactg ggagctgagt cagctgaccc atggtgtcac 1500

ccaactgggc ttctatgtcc tggacaggga tagcctcttc atcaatggct atgcacccca 1560

gaatttatca atccggggcg agtaccagat aaatttccac attgtcaact ggaacctcag 1620

taatccagac cccacatcct cagagtacat caccctgctg agggacatcc aggacaaggt 1680

caccacactc tacaaaggca gtcaactaca tgacacattc cgcttctgcc tggtcaccaa 1740

cttgacgatg gactccgtgt tggtcactgt caaggcattg ttctcctcca atttggaccc 1800

cagcctggtg gagcaagtct ttctagataa gaccctgaat gcctcattcc attggctggg 1860

ctccacctac cagttggtgg acatccatgt gacagaaatg gagtcatcag tttatcaacc 1920

aacaagcagc tccagcaccc agcacttcta cctgaatttc accatcacca acctaccata 1980

ttcccaggac aaagcccagc caggcaccac caattaccag aggaacaaaa ggaatattga 2040

ggatgcgctc aaccaactct tccgaaacag cagcatcaag agttattttt ctgactgtca 2100

agtttcaaca ttcaggtctg tccccaacag gcaccacacc ggggtggact ccctgtgtaa 2160

cttctcgcca ctggctcgga gagtagacag agttgccatc tatgaggaat ttctgcggat 2220

gacccggaat ggtacccagc tgcagaactt caccctggac aggagcagtg tccttgtgga 2280

tgggtatttt cccaacagaa atgagccctt aactgggaat tctgaccttc ccttctgggc 2340

tgtcatcctc atcggcttgg caggactcct gggactcatc acatgcctga tctgcggtgt 2400

cctggtgacc acccgccggc ggaagaagga aggagaatac aacgtccagc aacagtgccc 2460

aggctactac cagtcacacc tagacctgga ggatctgcaa tgactggaac ttgccggtgc 2520

ctggggtgcc tttcccccag ccagggtcca aagaagcttg gctggggcag aaataaacca 2580

tattggtcgg acacaaaaaa aaaaaaaa 2608

387

1761

Homo sapiens

387

ctgaacttca ccatcaacaa cctgcgctac atggcggaca tgggccaacc cggctccctc 60

aagttcaaca tcacagacaa cgtcatgaag cacctgctca gtcctttgtt ccagaggagc 120

agcctgggtg cacggtacac aggctgcagg gtcatcgcac taaggtctgt gaagaacggt 180

gctgagacac gggtggacct cctctgcagg taggtgcaga ggaggtccac ggcatcaccc 240

ggctgggccc ctactctctg gacaaagaca gcctctacct taacgctccc aagccagcca 300

ccacattcct gcctcctctg tcagaagcca caacagccat ggggtaccac ctgaagaccc 360

tcacactcaa cttcaccatc tccaatctcc agtattcacc agatatgggc aagggctcag 420

ctacattcaa ctccaccgag ggggtccttc agcacctgct cagacccttg ttccagaaga 480

gcagcatggg ccccttctac ttgggttgcc aactgatctc cctcaggcct gagaaggatg 540

gggcagccac tggtgtggac accacctgca cctaccaccc tgaccctgtg ggccccgggc 600

tggacataca gcagctttac tgggagctga gtcagctgac ccatggtgtc acccaactgg 660

gcttctatgt cctggacagg gatagcctct tcatcaatgg ctatgcaccc cagaatttat 720

caatccgggg cgagtaccag ataaatttcc acattgtcaa ctggaacctc agtaatccag 780

accccacatc ctcagagtac atcaccctgc tgagggacat ccaggacaag gtcaccacac 840

tctacaaagg cagtcaacta catgacacat tccgcttctg cctggtcacc aacttgacga 900

tggactccgt gttggtcact gtcaaggcat tgttctcctc caatttggac cccagcctgg 960

tggagcaagt ctttctagat aagaccctga atgcctcatt ccattggctg ggctccacct 1020

accagttggt ggacatccat gtgacagaaa tggagtcatc agtttatcaa ccaacaagca 1080

gctccagcac ccagcacttc tacctgaatt tcaccatcac caacctacca tattcccagg 1140

acaaagccca gccaggcacc accaattacc agaggaacaa aaggaatatt gaggatgcgc 1200

tcaaccaact cttccgaaac agcagcatca agagttattt ttctgactgt caagtttcaa 1260

cattcaggtc tgtccccaac aggcaccaca ccggggtgga ctccctgtgt aacttctcgc 1320

cactggctcg gagagtagac agagttgcca tctatgagga atttctgcgg atgacccgga 1380

atggtaccca gctgcagaac ttcaccctgg acaggagcag tgtccttgtg gatgggtatt 1440

ttcccaacag aaatgagccc ttaactggga attctgacct tcccttctgg gctgtcatcc 1500

tcatcggctt ggcaggactc ctgggactca tcacatgcct gatctgcggt gtcctggtga 1560

ccacccgccg gcggaagaag gaaggagaat acaacgtcca gcaacagtgc ccaggctact 1620

accagtcaca cctagacctg gaggatctgc aatgactgga acttgccggt gcctggggtg 1680

cctttccccc agccagggtc caaagaagct tggctggggc agaaataaac catattggtc 1740

ggacacaaaa aaaaaaaaaa a 1761

388

772

Homo sapiens

388

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser

65 70 75 80

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

85 90 95

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala

100 105 110

Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

115 120 125

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu

130 135 140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr

145 150 155 160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val

165 170 175

Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala

180 185 190

Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn

195 200 205

Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr

210 215 220

Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr

225 230 235 240

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

245 250 255

Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

260 265 270

Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

275 280 285

Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu

290 295 300

Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val

305 310 315 320

Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn

325 330 335

Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly

340 345 350

Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser

355 360 365

Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg

370 375 380

Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp

385 390 395 400

Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile

405 410 415

Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg

420 425 430

Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

435 440 445

Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr

450 455 460

Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His

465 470 475 480

Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser

485 490 495

Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val

500 505 510

Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro

515 520 525

Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly

530 535 540

Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val

545 550 555 560

Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu

565 570 575

Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser

580 585 590

Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu

595 600 605

Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp

610 615 620

Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys

625 630 635 640

Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe

645 650 655

Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys

660 665 670

Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe

675 680 685

Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr

690 695 700

Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln

705 710 715 720

Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile

725 730 735

Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn

740 745 750

Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Ala Pro His Arg Gly

755 760 765

Gly Leu Pro Val

770

389

833

Homo sapiens

389

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

5 10 15

Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala Ile

20 25 30

Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln

35 40 45

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly

50 55 60

Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr His

65 70 75 80

Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr

85 90 95

Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala

100 105 110

Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu

115 120 125

Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr

130 135 140

Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser

145 150 155 160

Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

165 170 175

Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Pro

180 185 190

Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu

195 200 205

Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp

210 215 220

Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val Pro

225 230 235 240

Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn Phe

245 250 255

Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly Ser

260 265 270

Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser Pro

275 280 285

Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val

290 295 300

Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp Leu

305 310 315 320

Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys

325 330 335

Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg Leu

340 345 350

Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn

355 360 365

Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr

370 375 380

Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His Leu

385 390 395 400

Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro

405 410 415

Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val Leu

420 425 430

Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro Phe

435 440 445

Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala

450 455 460

Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val Gly

465 470 475 480

Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

485 490 495

His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu

500 505 510

Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr

515 520 525

Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro

530 535 540

Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys Val

545 550 555 560

Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys

565 570 575

Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys Ala

580 585 590

Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe Leu

595 600 605

Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr Gln

610 615 620

Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln Pro

625 630 635 640

Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile Thr

645 650 655

Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr

660 665 670

Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg

675 680 685

Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe

690 695 700

Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys Asn

705 710 715 720

Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu Glu

725 730 735

Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu

740 745 750

Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe Pro Asn Arg Asn Glu

755 760 765

Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Leu Ile

770 775 780

Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly Val

785 790 795 800

Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln

805 810 815

Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp Leu

820 825 830

Gln

390

438

Homo sapiens

390

Met Gly Tyr His Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn

5 10 15

Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser

20 25 30

Thr Glu Gly Val Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser

35 40 45

Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro

50 55 60

Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His

65 70 75 80

Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu

85 90 95

Leu Ser Gln Leu Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu

100 105 110

Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser

115 120 125

Ile Arg Gly Glu Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu

130 135 140

Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp

145 150 155 160

Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp

165 170 175

Thr Phe Arg Phe Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu

180 185 190

Val Thr Val Lys Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val

195 200 205

Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu

210 215 220

Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser

225 230 235 240

Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu

245 250 255

Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro

260 265 270

Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu

275 280 285

Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys

290 295 300

Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val

305 310 315 320

Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val

325 330 335

Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu

340 345 350

Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe

355 360 365

Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp

370 375 380

Ala Val Ile Leu Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys

385 390 395 400

Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly

405 410 415

Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu

420 425 430

Asp Leu Glu Asp Leu Gln

435

391

2627

Homo sapiens

391

ccacgcgtcc gcccacgcgt ccggaaggca gcggcagctc cactcagcca gtacccagat 60

acgctgggaa ccttccccag ccatggcttc cctggggcag atcctcttct ggagcataat 120

tagcatcatc attattctgg ctggagcaat tgcactcatc attggctttg gtatttcagg 180

gagacactcc atcacagtca ctactgtcgc ctcagctggg aacattgggg aggatggaat 240

cctgagctgc acttttgaac ctgacatcaa actttctgat atcgtgatac aatggctgaa 300

ggaaggtgtt ttaggcttgg tccatgagtt caaagaaggc aaagatgagc tgtcggagca 360

ggatgaaatg ttcagaggcc ggacagcagt gtttgctgat caagtgatag ttggcaatgc 420

ctctttgcgg ctgaaaaacg tgcaactcac agatgctggc acctacaaat gttatatcat 480

cacttctaaa ggcaagggga atgctaacct tgagtataaa actggagcct tcagcatgcc 540

ggaagtgaat gtggactata atgccagctc agagaccttg cggtgtgagg ctccccgatg 600

gttcccccag cccacagtgg tctgggcatc ccaagttgac cagggagcca acttctcgga 660

agtctccaat accagctttg agctgaactc tgagaatgtg accatgaagg ttgtgtctgt 720

gctctacaat gttacgatca acaacacata ctcctgtatg attgaaaatg acattgccaa 780

agcaacaggg gatatcaaag tgacagaatc ggagatcaaa aggcggagtc acctacagct 840

gctaaactca aaggcttctc tgtgtgtctc ttctttcttt gccatcagct gggcacttct 900

gcctctcagc ccttacctga tgctaaaata atgtgccttg gccacaaaaa agcatgcaaa 960

gtcattgtta caacagggat ctacagaact atttcaccac cagatatgac ctagttttat 1020

atttctggga ggaaatgaat tcatatctag aagtctggag tgagcaaaca agagcaagaa 1080

acaaaaagaa gccaaaagca gaaggctcca atatgaacaa gataaatcta tcttcaaaga 1140

catattagaa gttgggaaaa taattcatgt gaactagaca agtgtgttaa gagtgataag 1200

taaaatgcac gtggagacaa gtgcatcccc agatctcagg gacctccccc tgcctgtcac 1260

ctggggagtg agaggacagg atagtgcatg ttctttgtct ctgaattttt agttatatgt 1320

gctgtaatgt tgctctgagg aagcccctgg aaagtctatc ccaacatatc cacatcttat 1380

attccacaaa ttaagctgta gtatgtaccc taagacgctg ctaattgact gccacttcgc 1440

aactcagggg cggctgcatt ttagtaatgg gtcaaatgat tcacttttta tgatgcttcc 1500

aaaggtgcct tggcttctct tcccaactga caaatgccaa agttgagaaa aatgatcata 1560

attttagcat aaacagagca gtcggcgaca ccgattttat aaataaactg agcaccttct 1620

ttttaaacaa acaaatgcgg gtttatttct cagatgatgt tcatccgtga atggtccagg 1680

gaaggacctt tcaccttgac tatatggcat tatgtcatca caagctctga ggcttctcct 1740

ttccatcctg cgtggacagc taagacctca gttttcaata gcatctagag cagtgggact 1800

cagctggggt gatttcgccc cccatctccg ggggaatgtc tgaagacaat tttggttacc 1860

tcaatgaggg agtggaggag gatacagtgc tactaccaac tagtggataa aggccaggga 1920

tgctgctcaa cctcctacca tgtacaggac gtctccccat tacaactacc caatccgaag 1980

tgtcaactgt gtcaggacta agaaaccctg gttttgagta gaaaagggcc tggaaagagg 2040

ggagccaaca aatctgtctg cttcctcaca ttagtcattg gcaaataagc attctgtctc 2100

tttggctgct gcctcagcac agagagccag aactctatcg ggcaccagga taacatctct 2160

cagtgaacag agttgacaag gcctatggga aatgcctgat gggattatct tcagcttgtt 2220

gagcttctaa gtttctttcc cttcattcta ccctgcaagc caagttctgt aagagaaatg 2280

cctgagttct agctcaggtt ttcttactct gaatttagat ctccagaccc ttcctggcca 2340

caattcaaat taaggcaaca aacatatacc ttccatgaag cacacacaga cttttgaaag 2400

caaggacaat gactgcttga attgaggcct tgaggaatga agctttgaag gaaaagaata 2460

ctttgtttcc agcccccttc ccacactctt catgtgttaa ccactgcctt cctggacctt 2520

ggagccacgg tgactgtatt acatgttgtt atagaaaact gattttagag ttctgatcgt 2580

tcaagagaat gattaaatat acatttccta caccaaaaaa aaaaaaa 2627

392

309

Homo sapiens

392

His Ala Ser Ala His Ala Ser Gly Arg Gln Arg Gln Leu His Ser Ala

5 10 15

Ser Thr Gln Ile Arg Trp Glu Pro Ser Pro Ala Met Ala Ser Leu Gly

20 25 30

Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile Ile Ile Leu Ala Gly

35 40 45

Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser Gly Arg His Ser Ile

50 55 60

Thr Val Thr Thr Val Ala Ser Ala Gly Asn Ile Gly Glu Asp Gly Ile

65 70 75 80

Leu Ser Cys Thr Phe Glu Pro Asp Ile Lys Leu Ser Asp Ile Val Ile

85 90 95

Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val His Glu Phe Lys Glu

100 105 110

Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met Phe Arg Gly Arg Thr

115 120 125

Ala Val Phe Ala Asp Gln Val Ile Val Gly Asn Ala Ser Leu Arg Leu

130 135 140

Lys Asn Val Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys Tyr Ile Ile

145 150 155 160

Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala

165 170 175

Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr

180 185 190

Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp

195 200 205

Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn Thr

210 215 220

Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met Lys Val Val Ser Val

225 230 235 240

Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser Cys Met Ile Glu Asn

245 250 255

Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val Thr Glu Ser Glu Ile

260 265 270

Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser Lys Ala Ser Leu Cys

275 280 285

Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu Leu Pro Leu Ser Pro

290 295 300

Tyr Leu Met Leu Lys

305

393

282

Homo sapiens

393

Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

5 10 15

Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser

20 25 30

Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly Asn Ile

35 40 45

Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile Lys Leu

50 55 60

Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val

65 70 75 80

His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met

85 90 95

Phe Arg Gly Arg Thr Ala Val Phe Ala Asp Gln Val Ile Val Gly Asn

100 105 110

Ala Ser Leu Arg Leu Lys Asn Val Gln Leu Thr Asp Ala Gly Thr Tyr

115 120 125

Lys Cys Tyr Ile Ile Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu

130 135 140

Tyr Lys Thr Gly Ala Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn

145 150 155 160

Ala Ser Ser Glu Thr Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln

165 170 175

Pro Thr Val Val Trp Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser

180 185 190

Glu Val Ser Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met

195 200 205

Lys Val Val Ser Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser

210 215 220

Cys Met Ile Glu Asn Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val

225 230 235 240

Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser

245 250 255

Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu

260 265 270

Leu Pro Leu Ser Pro Tyr Leu Met Leu Lys

275 280

394

20

Homo sapiens

394

Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

1 5 10 15

Ile Ile Leu Ala

20

395

20

Homo sapiens

395

Ile Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile

1 5 10 15

Ser Gly Arg His

20

396

20

Homo sapiens

396

Ile Ser Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly

1 5 10 15

Asn Ile Gly Glu

20

397

20

Homo sapiens

397

Gly Asn Ile Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp

1 5 10 15

Ile Lys Leu Ser

20

398

20

Homo sapiens

398

Asp Ile Lys Leu Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val

1 5 10 15

Leu Gly Leu Val

20

399

20

Homo sapiens

399

Val Leu Gly Leu Val His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser

1 5 10 15

Glu Gln Asp Glu

20

400

20

Homo sapiens

400

Ser Glu Gln Asp Glu Met Phe Arg Gly Arg Thr Ala Val Phe Ala Asp

1 5 10 15

Gln Val Ile Val

20

401

20

Homo sapiens

401

Asp Gln Val Ile Val Gly Asn Ala Ser Leu Arg Leu Lys Asn Val Gln

1 5 10 15

Leu Thr Asp Ala

20

402

21

Homo sapiens

402

Val Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys Tyr Ile Ile Thr Ser

1 5 10 15

Lys Gly Lys Gly Asn

20

403

20

Homo sapiens

403

Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala Phe Ser

1 5 10 15

Met Pro Glu Val

20

404

20

Homo sapiens

404

Ser Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr Leu

1 5 10 15

Arg Cys Glu Ala

20

405

20

Homo sapiens

405

Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp

1 5 10 15

Ala Ser Gln Val

20

406

20

Homo sapiens

406

Trp Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn

1 5 10 15

Thr Ser Phe Glu

20

407

20

Homo sapiens

407

Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met Lys Val Val

1 5 10 15

Ser Val Leu Tyr

20

408

20

Homo sapiens

408

Val Ser Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser Cys Met

1 5 10 15

Ile Glu Asn Asp

20

409

20

Homo sapiens

409

Met Ile Glu Asn Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val Thr

1 5 10 15

Glu Ser Glu Ile

20

410

20

Homo sapiens

410

Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser

1 5 10 15

Lys Ala Ser Leu

20

411

20

Homo sapiens

411

Ser Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala

1 5 10 15

Leu Leu Pro Leu

20

412

20

Homo sapiens

412

Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu Leu Pro Leu Ser Pro Tyr

1 5 10 15

Leu Met Leu Lys

20

413

35

Homo sapiens

413

Ile Ser Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly

1 5 10 15

Asn Ile Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile

20 25 30

Lys Leu Ser

35

414

35

Homo sapiens

414

Val Leu Gly Leu Val His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser

1 5 10 15

Glu Gln Asp Glu Met Phe Arg Gly Arg Thr Ala Val Phe Ala Asp Gln

20 25 30

Val Ile Val

35

415

65

Homo sapiens

415

Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala Phe Ser

1 5 10 15

Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr Leu Arg

20 25 30

Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp Ala Ser

35 40 45

Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn Thr Ser Phe

50 55 60

Glu

65

416

10

Homo sapiens

416

Lys Leu Ser Asp Ile Val Ile Gln Trp Leu

1 5 10

417

10

Homo sapiens

417

Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile

1 5 10

418

10

Homo sapiens

418

Leu Leu Asn Ser Lys Ala Ser Leu Cys Val

1 5 10

419

10

Homo sapiens

419

Ser Leu Cys Val Ser Ser Phe Phe Ala Ile

1 5 10

420

10

Homo sapiens

420

Val Leu Tyr Asn Val Thr Ile Asn Asn Thr

1 5 10

421

10

Homo sapiens

421

Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

1 5 10

422

10

Homo sapiens

422

Leu Leu Pro Leu Ser Pro Tyr Leu Met Leu

1 5 10

423

10

Homo sapiens

423

Cys Met Ile Glu Asn Asp Ile Ala Lys Ala

1 5 10

424

10

Homo sapiens

424

Lys Thr Gly Ala Phe Ser Met Pro Glu Val

1 5 10

425

10

Homo sapiens

425

Trp Ala Leu Leu Pro Leu Ser Pro Tyr Leu

1 5 10

426

10

Homo sapiens

426

Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile

1 5 10

427

10

Homo sapiens

427

Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys

1 5 10

428

10

Homo sapiens

428

Ala Leu Leu Pro Leu Ser Pro Tyr Leu Met

1 5 10

429

10

Homo sapiens

429

Gln Leu Leu Asn Ser Lys Ala Ser Leu Cys

1 5 10

430

10

Homo sapiens

430

Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile

1 5 10

431

10

Homo sapiens

431

Trp Leu Lys Glu Gly Val Leu Gly Leu Val

1 5 10

432

10

Homo sapiens

432

Leu Gln Leu Leu Asn Ser Lys Ala Ser Leu

1 5 10

433

10

Homo sapiens

433

Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile

1 5 10

434

10

Homo sapiens

434

Gly Ile Ser Gly Arg His Ser Ile Thr Val

1 5 10

435

10

Homo sapiens

435

Phe Glu Pro Asp Ile Lys Leu Ser Asp Ile

1 5 10

436

9

Homo sapiens

436

Ala Leu Leu Pro Leu Ser Pro Tyr Leu

1 5

437

9

Homo sapiens

437

Ser Leu Cys Val Ser Ser Phe Phe Ala

1 5

438

9

Homo sapiens

438

Ile Leu Phe Trp Ser Ile Ile Ser Ile

1 5

439

9

Homo sapiens

439

Gln Leu Leu Asn Ser Lys Ala Ser Leu

1 5

440

9

Homo sapiens

440

Lys Val Val Ser Val Leu Tyr Asn Val

1 5

441

9

Homo sapiens

441

Ile Leu Ala Gly Ala Ile Ala Leu Ile

1 5

442

9

Homo sapiens

442

Trp Leu Lys Glu Gly Val Leu Gly Leu

1 5

443

9

Homo sapiens

443

Ile Ile Leu Ala Gly Ala Ile Ala Leu

1 5

444

9

Homo sapiens

444

Asn Val Thr Met Lys Val Val Ser Val

1 5

445

9

Homo sapiens

445

Glu Met Phe Arg Gly Arg Thr Ala Val

1 5

446

9

Homo sapiens

446

Ala Val Phe Ala Asp Gln Val Ile Val

1 5

447

9

Homo sapiens

447

Leu Leu Pro Leu Ser Pro Tyr Leu Met

1 5

448

9

Homo sapiens

448

Leu Leu Asn Ser Lys Ala Ser Leu Cys

1 5

449

9

Homo sapiens

449