Smagulova Fatima, Brick Kevin, Pu Yongmei, Camerini-Otero R Daniel, Petukhova Galina V
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814, USA;
National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20814, USA.
Genes Dev. 2016 Feb 1;30(3):266-80. doi: 10.1101/gad.270009.115.
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.
减数分裂重组对于同源染色体的分离是必需的，并且对生育能力至关重要。在大多数哺乳动物中，引发减数分裂重组的DNA双链断裂（DSB）通过PRDM9蛋白的序列特异性结合被导向基因组位点的一个子集（热点）。PRDM9的DNA结合特异性的快速进化以及基因转换对PRDM9结合位点的逐渐侵蚀将随着时间的推移改变重组格局。为了更好地理解重组热点的进化更替及其后果，我们在具有不同Prdm9等位基因的小家鼠四个主要亚种及其F1杂种中绘制了DSB热点图谱。我们发现，热点侵蚀决定了杂种小鼠中某些Prdm9等位基因相对于其他等位基因的优先使用，并特别增加了在杂种中变得活跃的热点处的序列多样性。由于在这些热点处交叉不受青睐，我们提出由热点更替产生的序列分歧可能会对杂种中的重组造成障碍，潜在地导致生育力下降，并最终导致物种形成。
