Unexpectedly similar rates of nucleotide substitution found in male and female hominids (original) (raw)

Nature volume 406, pages 622–625 (2000)Cite this article

Abstract

In 1947, it was suggested that, in humans, the mutation rate is dramatically higher in the male germ line than in the female germ line1. This hypothesis has been supported by the observation that, among primates, Y-linked genes evolved more rapidly than homologous X-linked genes2,3,4,5,6. Based on these evolutionary studies, the ratio (αm) of male to female mutation rates in primates was estimated to be about 5. However, selection could have skewed sequence evolution in introns and exons7,8,9,10. In addition, some of the X–Y gene pairs studied lie within chromosomal regions with substantially divergent nucleotide sequences7,11,12. Here we directly compare human X and Y sequences within a large region with no known genes. Here the two chromosomes are 99% identical, and X–Y divergence began only three or four million years ago, during hominid evolution13,14,15. In apes, homologous sequences exist only on the X chromosome. We sequenced and compared 38.6 kb of this region from human X, human Y, chimpanzee X and gorilla X chromosomes. We calculated αm to be 1.7 (95% confidence interval 1.15–2.87), significantly lower than previous estimates in primates. We infer that, in humans and their immediate ancestors, male and female mutation rates were far more similar than previously supposed.

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Figure 1: Phylogenetic tree of nucleotide sequences.

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Acknowledgements

We thank A. Schwartz for identifying homologous X and Y-chromosomal BACs, colleagues at the Whitehead Institute/MIT Centre for Genome Research for sequencing those BACs, and J. Bradley, A. Chakravarti, B. Charlesworth, A. Clark, D. Haig, T. Kawaguchi, L. Kruglyak, F. Lewitter, Y.-F. Lim, D. Reich, W. Rice, S. Rozen, C. Tilford and J. Wang for comments on the manuscript. Supported in part by the NIH.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Whitehead Institute,
    Hacho B. Bohossian, Helen Skaletsky & David C. Page
  2. Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA
    Hacho B. Bohossian, Helen Skaletsky & David C. Page

Authors

  1. Hacho B. Bohossian
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  2. Helen Skaletsky
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  3. David C. Page
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Correspondence toDavid C. Page.

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Bohossian, H., Skaletsky, H. & Page, D. Unexpectedly similar rates of nucleotide substitution found in male and female hominids.Nature 406, 622–625 (2000). https://doi.org/10.1038/35020557

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