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Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition


In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex—the W and Y chromosomes1,2,3,4,5. By contrast, the sex chromosomes found in both sexes—the Z and X chromosomes—are assumed to have diverged little from their autosomal progenitors2. Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.

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Figure 1: The Z amplicon.
Figure 2: Independent origin of chicken Z and human X chromosomes.
Figure 3: Convergent gene gain on the chicken Z and human X chromosomes.

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Data deposits

Predicted Z-amplicon transcript sequences and the complete assembled sequence of the Z chromosome are available at (see Supplementary Table 5 for GenBank accession numbers).


  1. Muller, H. J. A gene for the fourth chromosome of Drosophila . J. Exp. Zool. 17, 325–336 (1914)

    Article  Google Scholar 

  2. Ohno, S. Sex Chromosomes and Sex-Linked Genes (Springer, 1967)

    Book  Google Scholar 

  3. Lahn, B. T. & Page, D. C. Four evolutionary strata on the human X chromosome. Science 286, 964–967 (1999)

    Article  CAS  Google Scholar 

  4. Skaletsky, H. et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423, 825–837 (2003)

    Article  ADS  CAS  Google Scholar 

  5. Ross, M. T. et al. The DNA sequence of the human X chromosome. Nature 434, 325–337 (2005)

    Article  ADS  CAS  Google Scholar 

  6. Nanda, I. et al. 300 million years of conserved synteny between chicken Z and human chromosome 9. Nature Genet. 21, 258–259 (1999)

    Article  CAS  Google Scholar 

  7. Nanda, I., Haaf, T., Schartl, M., Schmid, M. & Burt, D. W. Comparative mapping of Z-orthologous genes in vertebrates: implications for the evolution of avian sex chromosomes. Cytogenet. Genome Res. 99, 178–184 (2002)

    Article  CAS  Google Scholar 

  8. International Chicken Genome Sequencing Consortium Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432, 695–716 (2004)

    Article  Google Scholar 

  9. Grützner, F. et al. In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432, 913–917 (2004)

    Article  ADS  Google Scholar 

  10. Rens, W. et al. Resolution and evolution of the duck-billed platypus karyotype with an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex chromosome constitution. Proc. Natl Acad. Sci. USA 101, 16257–16261 (2004)

    Article  ADS  CAS  Google Scholar 

  11. Ezaz, T., Stiglec, R., Veyrunes, F. & Marshall Graves, J. A. Relationships between vertebrate ZW and XY sex chromosome systems. Curr. Biol. 16, R736–R743 (2006)

    Article  CAS  Google Scholar 

  12. Smith, J. J. & Voss, S. R. Bird and mammal sex-chromosome orthologs map to the same autosomal region in a salamander (Ambystoma). Genetics 177, 607–613 (2007)

    Article  CAS  Google Scholar 

  13. Hori, T. et al. Characterization of DNA sequences constituting the terminal heterochromatin of the chicken Z chromosome. Chromosome Res. 4, 411–426 (1996)

    Article  CAS  Google Scholar 

  14. Kasahara, M. et al. The medaka draft genome and insights into vertebrate genome evolution. Nature 447, 714–719 (2007)

    Article  ADS  CAS  Google Scholar 

  15. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)

    Article  ADS  CAS  Google Scholar 

  16. Scanlan, M. J., Simpson, A. J. & Old, L. J. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 4, 1 (2004)

    PubMed  Google Scholar 

  17. Wheeler, D. L. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 33, D39–D45 (2005)

    Article  ADS  CAS  Google Scholar 

  18. Saifl, G. M. & Chandra, H. S. An apparent excess of sex- and reproduction-related genes on the human X chromosome. Proc. R. Soc. Lond. B 266, 203–209 (1999)

    Article  Google Scholar 

  19. Wichman, H. A., Bussche, R. A., Hamilton, M. J. & Baker, R. J. Transposable elements and the evolution of genome organization in mammals. Genetica 86, 287–293 (1992)

    Article  CAS  Google Scholar 

  20. Wyckoff, G. J., Wang, W. & Wu, C. I. Rapid evolution of male reproductive genes in the descent of man. Nature 403, 304–309 (2000)

    Article  ADS  CAS  Google Scholar 

  21. Swanson, W. J. & Vacquier, V. D. The rapid evolution of reproductive proteins. Nature Rev. Genet. 3, 137–144 (2002)

    Article  CAS  Google Scholar 

  22. Rice, W. R. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38, 735–742 (1984)

    Article  Google Scholar 

  23. Filatov, D. A. Evolutionary history of Silene latifolia sex chromosomes revealed by genetic mapping of four genes. Genetics 170, 975 (2005)

    Article  CAS  Google Scholar 

  24. Handley, L. J. L., Ceplitis, H. & Ellegren, H. Evolutionary strata on the chicken Z chromosome: implications for sex chromosome evolution. Genetics 167, 367 (2004)

    Article  Google Scholar 

  25. Nicolas, M. et al. A gradual process of recombination restriction in the evolutionary history of the sex chromosomes in dioecious plants. PLoS Biol. 3, e4 (2005)

    Article  Google Scholar 

  26. Wallis, J. W. et al. A physical map of the chicken genome. Nature 432, 761–764 (2004)

    Article  ADS  CAS  Google Scholar 

  27. Morisson, M. et al. ChickRH6: a chicken whole-genome radiation hybrid panel. Genet. Sel. Evol. 34, 521–533 (2002)

    Article  CAS  Google Scholar 

  28. Saxena, R. et al. Four DAZ genes in two clusters found in the AZFc region of the human Y chromosome. Genomics 67, 256–267 (2000)

    Article  CAS  Google Scholar 

  29. Kent, W. J. BLAT–the BLAST-like alignment tool. Genome Res. 12, 656–664 (2002)

    Article  CAS  Google Scholar 

  30. Hubbard, T. J. et al. Ensembl 2009. Nucleic Acids Res. 37, D690–D697 (2009)

    Article  CAS  Google Scholar 

  31. Korf, I., Flicek, P., Duan, D. & Brent, M. R. Integrating genomic homology into gene structure prediction. Bioinformatics 17 (suppl. 1). S140–S148 (2001)

    Article  Google Scholar 

  32. Flicek, P., Keibler, E., Hu, P., Korf, I. & Brent, M. R. Leveraging the mouse genome for gene prediction in human: from whole-genome shotgun reads to a global synteny map. Genome Res. 13, 46–54 (2003)

    Article  CAS  Google Scholar 

  33. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)

    Article  CAS  Google Scholar 

  34. Lowe, T. M. & Eddy, S. R. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 25, 955–964 (1997)

    Article  CAS  Google Scholar 

  35. Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J. & Sayers, E. W. GenBank. Nucleic Acids Res. 37, D26–D31 (2009)

    Article  CAS  Google Scholar 

  36. Griffiths-Jones, S., Saini, H. K., van Dongen, S. & Enright, A. J. miRBase: tools for microRNA genomics. Nucleic Acids Res. 36, D154–D158 (2008)

    Article  CAS  Google Scholar 

  37. Smit, A. F. A., Hubley, R. & Green, P. RepeatMasker Open-3.0. 〈〉 (2007)

  38. Kuroda-Kawaguchi, T. et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nature Genet. 29, 279–286 (2001)

    Article  CAS  Google Scholar 

  39. Boardman, P. E. et al. A comprehensive collection of chicken cDNAs. Curr. Biol. 12, 1965–1969 (2002)

    Article  Google Scholar 

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We thank E. Rapoport for technical assistance, S. Repping and S. van Daalen for experimental advice, and E. Anderson, T. Endo, M. Gill, A. Hochwagen, C. Hongay, Y. Hu, J. Hughes, J. Marszalek, J. Mueller and Y. Soh for comments on the manuscript. We thank the Broad Institute Genome Sequencing Platform and Genome Sequencing and Analysis Program, F. Di Palma and K. Lindblad-Toh for making the unpublished data for Gasterosteus aculeatus available. This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute.

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Authors and Affiliations



D.W.B., H.S., W.C.W., S.R., R.K.W. and D.C.P. planned the project. D.W.B. and L.G.B. performed BAC mapping. D.W.B. performed RT–PCR analysis. T.G. and C.K. were responsible for finished BAC sequencing. D.W.B. and H.S. performed comparative sequence analyses. T.P. performed FISH analysis. E.R.M. performed 454 sequencing. D.W.B. and D.C.P. wrote the paper.

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Correspondence to David C. Page.

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The authors declare no competing financial interests.

Supplementary information

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This file contains Supplementary Figures 1-12 with legends (please note that Supplementary Figure 1 spans 24 pages), Supplementary Tables 1-5 and Supplementary Notes 1, which gives additional information about Supplementary Figure 12. (PDF 25983 kb)

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Bellott, D., Skaletsky, H., Pyntikova, T. et al. Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition. Nature 466, 612–616 (2010).

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