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.

Details

Title
A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination
Author
Li, Ran 1   VIAFID ORCID Logo  ; Bitoun, Emmanuelle 2   VIAFID ORCID Logo  ; Altemose, Nicolas 3   VIAFID ORCID Logo  ; Davies, Robert W 2 ; Davies, Benjamin 4   VIAFID ORCID Logo  ; Myers, Simon R 2   VIAFID ORCID Logo 

1  The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK; Department of Statistics, University of Oxford, Oxford, UK; Target Discovery Institute, NDM Research Building, University of Oxford, Oxford, UK 
2  The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK; Department of Statistics, University of Oxford, Oxford, UK 
3  The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK; Department of Statistics, University of Oxford, Oxford, UK; Department of Bioengineering, Stanley Hall, University of California, Berkeley, CA, USA 
4  The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK 
Pages
1-15
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11675-y
ProQuest document ID
2282428360
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.