Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

Nature Genetics volume 36, pages 642–646 (2004)Cite this article

Abstract

Sex chromosomes are subject to sex-specific selective evolutionary forces1,2. One model predicts that genes with sex-biased expression should be enriched on the X chromosome2,3,4,5. In agreement with Rice's hypothesis3, spermatogonial genes are over-represented on the X chromosome of mice6 and sex- and reproduction-related genes are over-represented on the human X chromosome7,8. Male-biased genes are under-represented on the X chromosome in worms and flies9,10,11, however. Here we show that mouse spermatogenesis genes are relatively under-represented on the X chromosome and female-biased genes are enriched on it. We used Spo11−/− mice blocked in spermatogenesis early in meiosis12 to evaluate the temporal pattern of gene expression in sperm development. Genes expressed before the Spo11 block are enriched on the X chromosome, whereas those expressed later in spermatogenesis are depleted. Inactivation of the X chromosome in male meiosis may be a universal driving force for X-chromosome demasculinization.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sex-specific genes are differentially represented on the X chromosome.
Figure 2: The X chromosome is enriched for genes expressed in female gonads but depleted of genes expressed in male gonads.
Figure 3: Genes expressed early and late in spermatogenesis are differentially represented on the X chromosome.
Figure 4: Genes expressed in rat spermatogonia or Sertoli cells are enriched on the X chromosome.
Figure 5: X-linked genes have a lower average expression in testis.

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Charlesworth, B. The evolution of chromosomal sex determination. Novartis Found. Symp. 244, 207–219 (2002).

    PubMed  Google Scholar 

  2. Vallender, E.J. & Lahn, B.T. How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26, 159–169 (2004).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  4. Fisher, R.A. The evolution of dominance. Biol. Rev. 6, 345–368 (1931).

    Article  Google Scholar 

  5. Rice, W.R. Sexually antagonistic genes: experimental evidence. Science 256, 1436–1439 (1992).

    Article  CAS  Google Scholar 

  6. Wang, P.J., Mccarrey, J.R., Yang, F. & Page, D.C. An abundance of X-linked genes expressed in spermatogonia. Nat. Genet. 27, 422–426 (2001).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Lercher, M.J., Urrutia, A.O. & Hurst, L.D. Evidence that the human X chromosome is enriched for male-specific but not female-specific genes. Mol. Biol. Evol. 20, 1113–1116 (2003).

    Article  CAS  Google Scholar 

  9. Parisi, M. et al. Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science 299, 697–700 (2003).

    Article  CAS  Google Scholar 

  10. Reinke, V. et al. A global profile of germline gene expression in C. elegans. Mol. Cell 6, 605–616 (2000).

    Article  CAS  Google Scholar 

  11. Ranz, J.M., Castillo-Davis, C.I., Meiklejohn, C.D. & Hartl, D.L. Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science 300, 1742–1745 (2003).

    Article  CAS  Google Scholar 

  12. Romanienko, P.J. & Camerini-Otero, R.D. The mouse Spo11 gene is required for meiotic chromosome synapsis. Mol. Cell 6, 975–987 (2000).

    Article  CAS  Google Scholar 

  13. Huminiecki, L., Lloyd, A.T. & Wolfe, K.H. Congruence of tissue expression profiles from Gene Expression Atlas, SAGEmap and TissueInfo databases. BMC Genomics 4, 31 (2003).

    Article  Google Scholar 

  14. Su, A.I. et al. Large-scale analysis of the human and mouse transcriptomes. Proc. Natl. Acad. Sci. USA 99, 4465–4470 (2002).

    Article  CAS  Google Scholar 

  15. Bono, H. et al. Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays. Genome Res. 13, 1318–1323 (2003).

    Article  CAS  Google Scholar 

  16. Fraser, L.R. & Dudley, K. New insights into the t-complex and control of sperm function. Bioessays 21, 304–312 (1999).

    Article  CAS  Google Scholar 

  17. Eddy, E.M. Male germ cell gene expression. Recent Prog. Horm. Res. 57, 103–128 (2002).

    Article  CAS  Google Scholar 

  18. Bellve, A.R. Purification, culture, and fractionation of spermatogenic cells. Methods Enzymol. 225, 84–113 (1993).

    Article  CAS  Google Scholar 

  19. Solari, A.J. The behavior of the XY pair in mammals. Int. Rev. Cytol. 38, 273–317 (1974).

    Article  CAS  Google Scholar 

  20. Mckee, B.D. & Handel, M.A. Sex chromosomes, recombination, and chromatin conformation. Chromosoma 102, 71–80 (1993).

    Article  CAS  Google Scholar 

  21. Lifschytz, E. & Lindsley, D.L. The role of X-chromosome inactivation during spermatogenesis. Proc. Natl. Acad. Sci. USA 69, 182–186 (1972).

    Article  CAS  Google Scholar 

  22. Baudat, F., Manova, K., Yuen, J.P., Jasin, M. & Keeney, S. Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol. Cell 6, 989–998 (2000).

    Article  CAS  Google Scholar 

  23. Schultz, N., Hamra, F.K. & Garbers, D.L. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc. Natl. Acad. Sci. USA 100, 12201–12206 (2003).

    Article  CAS  Google Scholar 

  24. Schlecht, U. et al. Expression profiling of Mammalian male meiosis and gametogenesis identifies novel candidate genes for roles in the regulation of fertility. Mol. Biol. Cell 15, 1031–1043 (2004).

    Article  CAS  Google Scholar 

  25. Goldstein, P. The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of male and hermaphrodite wild-type and him mutants. Chromosoma 86, 577–593 (1982).

    Article  CAS  Google Scholar 

  26. Kelly, W.G. et al. X-chromosome silencing in the germline of C. elegans. Development 129, 479–492 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Huynh, K.D. & Lee, J.T. Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. Nature 426, 857–862 (2003).

    Article  CAS  Google Scholar 

  28. Stekel, D.J., Git, Y. & Falciani, F. The comparison of gene expression from multiple cDNA libraries. Genome Res. 10, 2055–2061 (2000).

    Article  CAS  Google Scholar 

  29. Tanaka, T.S. et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc. Natl. Acad. Sci. USA 97, 9127–9132 (2000).

    Article  Google Scholar 

  30. Tusher, V.G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA 98, 5116–5121 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank P. Hsieh and B. Oliver for critically reading the manuscript, the members of the Camerini-Otero lab for discussions, L. Robinson and L. Moore for their help and M. Primig for communicating results before publication.

Author information

Author notes

  1. Peter J Romanienko

    Present address: Developmental Biology Program, Mouse Genetics Core, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, New York, 10021, USA

  2. Pavel P Khil and Natalya A Smirnova: These authors contributed equally to this work.

Authors and Affiliations

  1. Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, 5 Memorial Drive, Bethesda, 20892, Maryland, USA

    Pavel P Khil, Natalya A Smirnova, Peter J Romanienko & R Daniel Camerini-Otero

Authors
  1. Pavel P Khil
    View author publications

    Search author on:PubMed Google Scholar

  2. Natalya A Smirnova
    View author publications

    Search author on:PubMed Google Scholar

  3. Peter J Romanienko
    View author publications

    Search author on:PubMed Google Scholar

  4. R Daniel Camerini-Otero
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to R Daniel Camerini-Otero.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khil, P., Smirnova, N., Romanienko, P. et al. The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation. Nat Genet 36, 642–646 (2004). https://doi.org/10.1038/ng1368

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/ng1368

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing