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Abundant gene conversion between arms of palindromes in human and ape Y chromosomes

Abstract

Eight palindromes comprise one-quarter of the euchromatic DNA of the male-specific region of the human Y chromosome, the MSY1. They contain many testis-specific genes and typically exhibit 99.97% intra-palindromic (arm-to-arm) sequence identity1. This high degree of identity could be interpreted as evidence that the palindromes arose through duplication events that occurred about 100,000 years ago. Using comparative sequencing in great apes, we demonstrate here that at least six of these MSY palindromes predate the divergence of the human and chimpanzee lineages, which occurred about 5 million years ago. The arms of these palindromes must have subsequently engaged in gene conversion, driving the paired arms to evolve in concert. Indeed, analysis of MSY palindrome sequence variation in existing human populations provides evidence of recurrent arm-to-arm gene conversion in our species. We conclude that during recent evolution, an average of approximately 600 nucleotides per newborn male have undergone Y–Y gene conversion, which has had an important role in the evolution of multi-copy testis gene families in the MSY.

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Figure 1: Sequence comparison of human and ape MSY palindromes.
Figure 2: Site in CDY1 showing evidence of multiple independent gene conversion events.

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References

  1. 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  PubMed  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. Agulnik, A. I. et al. Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations. Hum. Mol. Genet. 7, 1371–1377 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. Reijo, R. et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genet. 10, 383–393 (1995)

    Article  CAS  PubMed  Google Scholar 

  5. Glaser, B. et al. Simian Y chromosomes: species-specific rearrangements of DAZ, RBM, and TSPY versus contiguity of PAR and SRY. Mamm. Genome 9, 226–231 (1998)

    Article  CAS  PubMed  Google Scholar 

  6. Makova, K. D. & Li, W. H. Strong male-driven evolution of DNA sequences in humans and apes. Nature 416, 624–626 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Szostak, J. W., Orr-Weaver, T. L., Rothstein, R. J. & Stahl, F. W. The double-strand-break repair model for recombination. Cell 33, 25–35 (1983)

    Article  CAS  PubMed  Google Scholar 

  8. Jackson, J. A. & Fink, G. R. Gene conversion between duplicated genetic elements in yeast. Nature 292, 306–311 (1981)

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Underhill, P. A. et al. The phylogeography of Y chromosome binary haplotypes and the origins of modern human populations. Ann. Hum. Genet. 65, 43–62 (2001)

    Article  CAS  PubMed  Google Scholar 

  10. Murti, J. R., Bumbulis, M. & Schimenti, J. C. High-frequency germ line gene conversion in transgenic mice. Mol. Cell. Biol. 12, 2545–2552 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Johnson, R. D. & Jasin, M. Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells. EMBO J. 19, 3398–3407 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bailey, J. A. et al. Recent segmental duplications in the human genome. Science 297, 1003–1007 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  13. International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)

    Article  ADS  Google Scholar 

  14. Small, K., Iber, J. & Warren, S. T. Emerin deletion reveals a common X-chromosome inversion mediated by inverted repeats. Nature Genet. 16, 95–99 (1997)

    Article  Google Scholar 

  15. Aradhya, S. et al. Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Hum. Mol. Genet. 10, 2557–2567 (2001)

    Article  CAS  PubMed  Google Scholar 

  16. Rochette, C. F., Gilbert, N. & Simard, L. R. SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens. Hum. Genet. 108, 255–266 (2001)

    Article  CAS  PubMed  Google Scholar 

  17. Deeb, S. S., Jorgensen, A. L., Battisti, L., Iwasaki, L. & Motulsky, A. G. Sequence divergence of the red and green visual pigments in great apes and humans. Proc. Natl Acad. Sci. USA 91, 7262–7266 (1994)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhou, Y.-H. & Li, W.-H. Gene conversion and natural selection in the evolution of X-linked color vision genes in higher primates. Mol. Biol. Evol. 18, 780–783 (1996)

    Article  Google Scholar 

  19. Charlesworth, B. & Charlesworth, D. The degeneration of Y chromosomes. Phil. Trans. R. Soc. Lond. B 355, 1563–1572 (2000)

    Article  CAS  MATH  Google Scholar 

  20. Bohossian, H. B., Skaletsky, H. & Page, D. C. Unexpectedly similar rates of nucleotide substitution found in male and female hominids. Nature 406, 622–625 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Kumar, S. & Hedges, S. B. A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998)

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Fujiyama, A. et al. Construction and analysis of a human-chimpanzee comparative clone map. Science 295, 131–134 (2002)

    Article  ADS  PubMed  Google Scholar 

  23. Thompson, J. D., Higgins, D. G. & Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Ohta, T. Allelic and nonallelic homology of a supergene family. Proc. Natl Acad. Sci. USA 79, 3251–3254 (1982)

    Article  ADS  MathSciNet  CAS  PubMed  PubMed Central  MATH  Google Scholar 

  26. Casanova, M. et al. A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance. Science 230, 1403–1406 (1985)

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Underhill, P. A. et al. Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography. Genome Res. 7, 996–1005 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shen, P. et al. Population genetic implications from sequence variation in four Y chromosome genes. Proc. Natl Acad. Sci. USA 97, 7354–7359 (2000)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank R. K. Alagappan and L. G. Brown for technical contributions; N. A. Ellis, M. F. Hammer, T. Jenkins and P. A. Underhill for assistance with genealogical studies; H. M. McClure and Yerkes Regional Primate Research Center for samples; C. Disteche, A. E. Donnenfeld, J. H. Hersh, T. Jenkins, P. G. McDonough, B. McGillivray, R. D. Oates, P. Patrizio, R. Rosenfield, L. Shapiro, S. Silber, M. C. Summers, J. Weissenbach, B. Whitmire and S. Yang for patient samples; and J. E. Alfoldi, B. Charlesworth, A. G. Clark, J. Koubova, J. Lange, B. Levy, T. L. Orr-Weaver, S. Repping, W. R. Rice and J. Saionz for comments on the manuscript. This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute.

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Correspondence to David C. Page.

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Rozen, S., Skaletsky, H., Marszalek, J. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003). https://doi.org/10.1038/nature01723

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