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A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination
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A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination
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Journal Article
A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination
2019
Overview
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.
During meiotic recombination, genetic information is transferred or exchanged between parental chromosome copies. Using a large hybrid mouse pedigree, the authors generated high-resolution maps of these transfer/exchange events and discovered new properties governing their processing and resolution.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/15
/ 45/23
/ 64
/ 64/60
/ Alleles
/ Animals
/ Cell Cycle Proteins - genetics
/ DNA
/ Female
/ Genomes
/ Histone-Lysine N-Methyltransferase - genetics
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Male
/ Meiosis
/ Mice
/ Phosphate-Binding Proteins - genetics
/ Polymorphism, Single Nucleotide
/ Repair
/ Science
/ Yeast
