Letter | Published:

Independent specialization of the human and mouse X chromosomes for the male germ line

Nature Genetics volume 45, pages 10831087 (2013) | Download Citation

Abstract

We compared the human and mouse X chromosomes to systematically test Ohno's law, which states that the gene content of X chromosomes is conserved across placental mammals1. First, we improved the accuracy of the human X-chromosome reference sequence through single-haplotype sequencing of ampliconic regions. The new sequence closed gaps in the reference sequence, corrected previously misassembled regions and identified new palindromic amplicons. Our subsequent analysis led us to conclude that the evolution of human and mouse X chromosomes was bimodal. In accord with Ohno's law, 94–95% of X-linked single-copy genes are shared by humans and mice; most are expressed in both sexes. Notably, most X-ampliconic genes are exceptions to Ohno's law: only 31% of human and 22% of mouse X-ampliconic genes had orthologs in the other species. X-ampliconic genes are expressed predominantly in testicular germ cells, and many were independently acquired since divergence from the common ancestor of humans and mice, specializing portions of their X chromosomes for sperm production.

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Acknowledgements

We thank D. Albracht, J. Collins, M. Gill, N. Koutseva, C. Kremitzki, A. van der Veen and J. Wood for technical assistance and D. Bellott, R. Desgraz, G. Dokshin, T. Endo, A. Godfrey, Y. Hu, J. Hughes, M. Kojima, B. Lesch, L. Okumura, K. Romer and Y. Soh for comments on the manuscript. This work was supported by the US National Institutes of Health and the Howard Hughes Medical Institute.

Author information

Affiliations

  1. Whitehead Institute, Cambridge, Massachusetts, USA.

    • Jacob L Mueller
    • , Helen Skaletsky
    • , Laura G Brown
    • , Sara Zaghlul
    •  & David C Page
  2. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Helen Skaletsky
    • , Laura G Brown
    •  & David C Page
  3. The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Susan Rock
    • , Tina Graves
    • , Wesley C Warren
    •  & Richard K Wilson
  4. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Katherine Auger
  5. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • David C Page

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Contributions

J.L.M., H.S., W.C.W., R.K.W. and D.C.P. planned the project. J.L.M. and L.G.B. performed BAC mapping. J.L.M. performed RNA deep sequencing. T.G., S.R., K.A. and S.Z. were responsible for finished BAC sequencing. J.L.M. and H.S. performed sequence analyses. J.L.M. and D.C.P. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David C Page.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Note, Supplementary Figures 1–6 and Supplementary Tables 1, 5 and 9

Excel files

  1. 1.

    Supplementary Table 2

    Genes shared between human and mouse X chromosomes

  2. 2.

    Supplementary Table 3

    Human X-linked genes with no detectable ortholog on the mouse X chromosome

  3. 3.

    Supplementary Table 4

    Mouse X-linked genes with no detectable ortholog on the human X chromosome

  4. 4.

    Supplementary Table 6

    Tissue expression of X-linked genes shared between human and mouse

  5. 5.

    Supplementary Table 7

    Expression patterns of independently acquired human X-linked genes

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    Supplementary Table 8

    Expression patterns of independently acquired mouse X-linked genes

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    Supplementary Table 10

    Expression patterns of all human autosomal genes

  8. 8.

    Supplementary Table 11

    Expression patterns of all mouse autosomal genes

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    Supplementary Table 12

    All OMIM X-linked phenotypes where the molecular basis is known

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    Supplementary Table 13

    Expression patterns between the sexes, in the heart and kidney, of human genes that follow Ohno's law

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    Supplementary Table 14

    Expression patterns between the sexes, in the heart and kidney, of mouse genes that follow Ohno's law

About this article

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DOI

https://doi.org/10.1038/ng.2705

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