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A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination

Author

Listed:
  • Ran Li

    (Roosevelt Drive, University of Oxford
    University of Oxford
    University of Oxford)

  • Emmanuelle Bitoun

    (Roosevelt Drive, University of Oxford
    University of Oxford)

  • Nicolas Altemose

    (Roosevelt Drive, University of Oxford
    University of Oxford
    University of California)

  • Robert W. Davies

    (Roosevelt Drive, University of Oxford
    University of Oxford)

  • Benjamin Davies

    (Roosevelt Drive, University of Oxford)

  • Simon R. Myers

    (Roosevelt Drive, University of Oxford
    University of Oxford)

Abstract

During meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.

Suggested Citation

  • Ran Li & Emmanuelle Bitoun & Nicolas Altemose & Robert W. Davies & Benjamin Davies & Simon R. Myers, 2019. "A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11675-y
    DOI: 10.1038/s41467-019-11675-y
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