The evolutionary turnover of recombination hot spots contributes to speciation in mice

Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 prot...

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Bibliographic Details
Published inGenes & development Vol. 30; no. 3; pp. 266 - 280
Main Authors Smagulova, Fatima, Brick, Kevin, Pu, Yongmei, Camerini-Otero, R Daniel, Petukhova, Galina V
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.02.2016
Subjects
Alleles
Animals
Biological Evolution
DNA Breaks, Double-Stranded
Genetic Speciation
Histone-Lysine N-Methyltransferase - genetics
Histone-Lysine N-Methyltransferase - metabolism
Hybridization, Genetic
Life Sciences
Mice - classification
Mice - genetics
Mus musculus
Protein Binding
Recombination, Genetic - genetics
Research Paper
DSB hot spots
Prdm9
meiosis
recombination hot spots
homologous recombination
hybrid sterility
speciation
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Summary:Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 protein. Rapid evolution of the DNA-binding specificity of PRDM9 and gradual erosion of PRDM9-binding sites by gene conversion will alter the recombination landscape over time. To better understand the evolutionary turnover of recombination hot spots and its consequences, we mapped DSB hot spots in four major subspecies of Mus musculus with different Prdm9 alleles and in their F1 hybrids. We found that hot spot erosion governs the preferential usage of some Prdm9 alleles over others in hybrid mice and increases sequence diversity specifically at hot spots that become active in the hybrids. As crossovers are disfavored at such hot spots, we propose that sequence divergence generated by hot spot turnover may create an impediment for recombination in hybrids, potentially leading to reduced fertility and, eventually, speciation.
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PMCID: PMC4743057
These authors contributed equally to this work.
Present address: UMR1085-Irset, Inserm, 35042 Rennes, France.
ISSN:0890-9369
1549-5477
1549-5477
DOI:10.1101/gad.270009.115