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 multicopy testis genes showing postmeiotic expression

Abstract

According to the prevailing view, mammalian X chromosomes are enriched in spermatogenesis genes expressed before meiosis1,2,3 and deficient in spermatogenesis genes expressed after meiosis2,3. The paucity of postmeiotic genes on the X chromosome has been interpreted as a consequence of meiotic sex chromosome inactivation (MSCI)—the complete silencing of genes on the XY bivalent at meiotic prophase4,5. Recent studies have concluded that MSCI-initiated silencing persists beyond meiosis6,7,8 and that most genes on the X chromosome remain repressed in round spermatids7. Here, we report that 33 multicopy gene families, representing 273 mouse X-linked genes, are expressed in the testis and that this expression is predominantly in postmeiotic cells. RNA FISH and microarray analysis show that the maintenance of X chromosome postmeiotic repression is incomplete. Furthermore, X-linked multicopy genes exhibit a similar degree of expression as autosomal genes. Thus, not only is the mouse X chromosome enriched for spermatogenesis genes functioning before meiosis, but in addition, 18% of mouse X-linked genes are expressed in postmeiotic cells.

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

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

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

Figure 1: Mouse X chromosome ampliconic regions containing testis-expressed genes.
Figure 2: Mouse X chromosome ampliconic and nonampliconic multicopy genes show testis-biased expression, as shown by RT-PCR.
Figure 3: Mouse X chromosome ampliconic and nonampliconic multicopy genes are expressed predominantly in germ cells during postmeiotic spermatogenesis, as shown by RT-PCR.
Figure 4: Multicopy ampliconic genes show a greater degree of reactivation in round spermatids than single-copy genes.
Figure 5: Microarray analyses of single-copy and multicopy genes on the X chromosome.

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. 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 

  2. Khil, P.P., Smirnova, N.A., Romanienko, P.J. & Camerini-Otero, R.D. 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).

    Article  CAS  Google Scholar 

  3. Reinke, V. Sex and the genome. Nat. Genet. 36, 548–549 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Turner, J.M. Meiotic sex chromosome inactivation. Development 134, 1823–1831 (2007).

    Article  CAS  Google Scholar 

  6. Greaves, I.K., Rangasamy, D., Devoy, M., Marshall Graves, J.A. & Tremethick, D.J. The X and Y chromosomes assemble into H2A.Z-containing facultative heterochromatin following meiosis. Mol. Cell. Biol. 26, 5394–5405 (2006).

    Article  CAS  Google Scholar 

  7. Namekawa, S.H. et al. Postmeiotic sex chromatin in the male germline of mice. Curr. Biol. 16, 660–667 (2006).

    Article  CAS  Google Scholar 

  8. Turner, J.M., Mahadevaiah, S.K., Ellis, P.J., Mitchell, M.J. & Burgoyne, P.S. Pachytene asynapsis drives meiotic sex chromosome inactivation and leads to substantial postmeiotic repression in spermatids. Dev. Cell 10, 521–529 (2006).

    Article  CAS  Google Scholar 

  9. Warburton, P.E., Giordano, J., Cheung, F., Gelfand, Y. & Benson, G. Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res. 14, 1861–1869 (2004).

    Article  CAS  Google Scholar 

  10. Eichler, E.E., Clark, R.A. & She, X. An assessment of the sequence gaps: unfinished business in a finished human genome. Nat. Rev. Genet. 5, 345–354 (2004).

    Article  CAS  Google Scholar 

  11. Mroz, K., Carrel, L. & Hunt, P.A. Germ cell development in the XXY mouse: evidence that X chromosome reactivation is independent of sexual differentiation. Dev. Biol. 207, 229–238 (1999).

    Article  CAS  Google Scholar 

  12. Mazeyrat, S. et al. A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Nat. Genet. 29, 49–53 (2001).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  14. Kimura, T. et al. Mouse germ cell-less as an essential component for nuclear integrity. Mol. Cell. Biol. 23, 1304–1315 (2003).

    Article  CAS  Google Scholar 

  15. Govin, J. et al. Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis. J. Cell Biol. 176, 283–294 (2007).

    Article  CAS  Google Scholar 

  16. Wang, P.J., Page, D.C. & McCarrey, J.R. Differential expression of sex-linked and autosomal germ-cell-specific genes during spermatogenesis in the mouse. Hum. Mol. Genet. 14, 2911–2918 (2005).

    Article  CAS  Google Scholar 

  17. Westbrook, V.A. et al. Spermatid-specific expression of the novel X-linked gene product SPAN-X localized to the nucleus of human spermatozoa. Biol. Reprod. 63, 469–481 (2000).

    Article  CAS  Google Scholar 

  18. Westbrook, V.A. et al. Hominoid-specific SPANXA/D genes demonstrate differential expression in individuals and protein localization to a distinct nuclear envelope domain during spermatid morphogenesis. Mol. Hum. Reprod. 12, 703–716 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Waterston, R.H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

    Article  CAS  Google Scholar 

  21. 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 

Download references

Acknowledgements

We thank J. Alfoldi, D. Bellott, P. Burgoyne, H. Byers, J. Hughes, J. Lange, L. Reynard, S. Rozen and H. Skaletsky for helpful comments on the manuscript; D. Bellott, M. Gill, Y. Hu, J. Hughes and H. Skaletsky for technical advice; and P. Burgoyne and M. Mitchell for the Uty transgenic line. This work was supported by the Medical Research Council, US National Institutes of Health grant HD000257 (to D.C.P.), including fellowship F32HD052379 (to J.L.M.), and the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Contributions

J.L.M., J.M.A.T., S.K.M. and P.E.W. identified amplicons and multicopy genes. J.L.M., J.M.A.T. and S.K.M. carried out RT-PCRs and RNA FISH. J.L.M. and P.J.P. did microarray and statistical analysis. The paper was written by J.L.M., J.M.A.T. and D.C.P.

Corresponding authors

Correspondence to Jacob L Mueller or James M A Turner.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Tables 1–5 (PDF 1283 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mueller, J., Mahadevaiah, S., Park, P. et al. The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression. Nat Genet 40, 794–799 (2008). https://doi.org/10.1038/ng.126

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.126

This article is cited by

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