title: The evolutionary turnover of recombination hot spots contributes to speciation in mice.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814, USA;
authors.forename: Fatima
authors.initials: F
authors.lastname: Smagulova
authors.affiliation: National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20814, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Brick
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814, USA;
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Pu
authors.affiliation: National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20814, USA.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814, USA;
authors.forename: Galina V
authors.initials: GV
authors.lastname: Petukhova
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D053903:DNA Breaks, Double-Stranded; D049810:Genetic Speciation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006824:Hybridization, Genetic; D051379:Mice / Q000145:classification* / Q000235:genetics*; D011485:Protein Binding; D011995:Recombination, Genetic / Q000235:genetics*
chemical_list: D011495:Histone-Lysine N-Methyltransferase; C534829:prdm9 protein, mouse
keywords: DSB hot spots; Prdm9; homologous recombination; hybrid sterility; meiosis; recombination hot spots; speciation
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