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:

An initiation site for meiotic crossing-over and gene conversion in the mouse

Nature Genetics volume 32, pages 296–299 (2002)Cite this article

This article has been updated

Abstract

During meiosis, the reductional segregation of homologous chromosomes at the first meiotic division requires reciprocal exchange (crossing over) between homologs1. The number of crossovers is tightly regulated (one to two per homolog in mice2), and their distribution in the genome is not random—recombination 'hot' and 'cold' regions can be identified3,4. We developed a molecular assay to study these events directly in mouse germ cells. This analysis was developed with reference to the proteosome subunit β type 9 (Psmb9, previously called Lmp2) hot-spot region identified through genetic analysis5,6. Here we show that this hot spot is an initiation site of meiotic recombination on the basis of two observations: (i) crossover density is maximal in an interval of 210 bp and decreases on both sides of this region; (ii) a high frequency of gene conversion is found in the region of highest crossover density. We then used this strategy to carry out the first temporal analysis of meiotic recombination in mouse spermatogenesis and demonstrate that crossover events occur during the pachytene stage of meiotic prophase.

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
Buy now

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

Figure 1: Strategies to detect recombinant molecules.
Figure 2: Detection of crossover molecules.
Figure 3: Mapping of exchange points in crossover molecules.
Figure 4: Timing of the formation of B10–R209 crossover molecules.

Similar content being viewed by others

Change history

  • 01 October 2002

    This was incorrect in AOP and the October issue. Replaced incorrect Table A with corrected Web Table A.

References

  1. Roeder, G.S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600–2621 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Lawrie, N.M., Tease, C. & Hulten, M.A. Chiasma frequency, distribution and interference maps of mouse autosomes. Chromosoma 104, 308–314 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Lichten, M. & Goldman, A.S. Meiotic recombination hotspots. Annu. Rev. Genet. 29, 423–444 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Petes, T.D. Meiotic recombination hot spots and cold spots. Nat. Rev. Genet. 2, 360–369 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Shiroishi, T., Koide, T., Yoshino, M., Sagai, T. & Moriwaki, K. Hotspots of homologous recombination in mouse meiosis. Adv. Biophys. 31, 119–132 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Shiroishi, T. et al. Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex. Immunogenetics 31, 79–88 (1990).

    Article  CAS  PubMed  Google Scholar 

  7. Shiroishi, T., Sagai, T., Hanzawa, N., Gotoh, H. & Moriwaki, K. Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse. EMBO J. 10, 681–686 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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 

  9. Goetz, P., Chandley, A.C. & Speed, R.M. Morphological and temporal sequence of meiotic prophase development at puberty in the male mouse. J. Cell Sci. 65, 249–263 (1984).

    CAS  PubMed  Google Scholar 

  10. Mizuno, K., Koide, T., Sagai, T., Moriwaki, K. & Shiroishi, T. Molecular analysis of a recombinational hotspot adjacent to Lmp2 gene in the mouse MHC: fine location and chromatin structure. Mamm. Genome 7, 490–496 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Detloff, P., White, M.A. & Petes, T.D. Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae. Genetics 132, 113–123 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Schultes, N.P. & Szostak, J.W. Decreasing gradients of gene conversion on both sides of the initiation site for meiotic recombination at the ARG4 locus in yeast. Genetics 126, 813–822 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Borts, R.H. & Haber, J.E. Length and distribution of meiotic gene conversion tracts and crossovers in Saccharomyces cerevisiae. Genetics 123, 69–80 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Symington, L.S., Brown, A., Oliver, S.G., Greenwell, P. & Petes, T.D. Genetic analysis of a meiotic recombination hotspot on chromosome III of Saccharomyces cerevisiae. Genetics 128, 717–727 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Jeffreys, A.J., Kauppi, L. & Neumann, R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nature Genet. 29, 217–222 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Baker, S.M. et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nature Genet. 13, 336–342 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. Anderson, L.K., Reeves, A., Webb, L.M. & Ashley, T. Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of Mlh1 protein. Genetics 151, 1569–1579 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Cobb, J., Cargile, B. & Handel, M.A. Acquisition of competence to condense metaphase I chromosomes during spermatogenesis. Dev. Biol. 205, 49–64 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Jeffreys, A.J., Neumann, R. & Wilson, V. Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60, 473–485 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Peters, A.H., Plug, A.W., van Vugt, M.J. & de Boer, P. A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res. 5, 66–68 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Jeffreys, A.J., Ritchie, A. & Neumann, R. High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot. Hum. Mol. Genet. 9, 725–733 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank C. Ferraz for assistance in DNA sequencing; C. Heyting and P. de Boer for advice on testis cell preparation and spreading; C. Heyting and M.A. Handel for providing Sycp3 and H1t antibodies; J. Buard for advice on ASO–PCR; T. Shiroishi for providing the mouse strains and stimulating discussions about the project; and C. Mézard, H. te Riele and C. White for comments on the manuscript. This work was supported by research grants from the Centre National de la Recherche Scientifique (ATIPE program), the Association pour la Recherche contre le Cancer, the Fondation pour la Recherche Médicale and the Commissariat à l'Energie Atomique.

Author information

Authors and Affiliations

  1. Institut de Génétique Humaine, UPR1142/CNRS, 141 rue de la Cardonille, 34396 cedex 05, Montpellier, France

    Hélène Guillon & Bernard de Massy

Authors
  1. Hélène Guillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernard de Massy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard de Massy.

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

Guillon, H., de Massy, B. An initiation site for meiotic crossing-over and gene conversion in the mouse. Nat Genet 32, 296–299 (2002). https://doi.org/10.1038/ng990

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng990

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