The Jackson Laboratory, 600 Main Street, Bar Harbor, ME.
Graduate School of Biomedical Sciences, Tufts University, 136 Harrison Ave, Boston, MA.
Mol Biol Evol. 2023 Jan 4;40(1). doi: 10.1093/molbev/msac267.
Meiotic recombination is an important evolutionary force and an essential meiotic process. In many species, recombination events concentrate into hotspots defined by the site-specific binding of PRMD9. Rapid evolution of Prdm9's zinc finger DNA-binding array leads to remarkably abrupt shifts in the genomic distribution of hotspots between species, but the question of how Prdm9 allelic variation shapes the landscape of recombination between populations remains less well understood. Wild house mice (Mus musculus) harbor exceptional Prdm9 diversity, with >150 alleles identified to date, and pose a particularly powerful system for addressing this open question. We employed a coalescent-based approach to construct broad- and fine-scale sex-averaged recombination maps from contemporary patterns of linkage disequilibrium in nine geographically isolated wild house mouse populations, including multiple populations from each of three subspecies. Comparing maps between wild mouse populations and subspecies reveals several themes. First, we report weak fine- and broad-scale recombination map conservation across subspecies and populations, with genetic divergence offering no clear prediction for recombination map divergence. Second, most hotspots are unique to one population, an outcome consistent with minimal sharing of Prdm9 alleles between surveyed populations. Finally, by contrasting aggregate hotspot activity on the X versus autosomes, we uncover evidence for population-specific differences in the degree and direction of sex dimorphism for recombination. Overall, our findings illuminate the variability of both the broad- and fine-scale recombination landscape in M. musculus and underscore the functional impact of Prdm9 allelic variation in wild mouse populations.
减数分裂重组是一种重要的进化力量和必要的减数分裂过程。在许多物种中，重组事件集中在由 PRMD9 特异性结合定义的热点中。Prdm9 的锌指 DNA 结合结构域的快速进化导致热点在物种间的基因组分布发生显著变化，但 Prdm9 等位基因变异如何塑造种群间重组景观的问题仍然知之甚少。野生家鼠（Mus musculus）拥有异常丰富的 Prdm9 多样性，迄今为止已鉴定出超过 150 个等位基因，是解决这一开放性问题的特别有力系统。我们采用基于合并的方法，从九个地理隔离的野生家鼠种群的连锁不平衡当代模式构建了广泛和精细的性别平均重组图谱，包括来自三个亚种的多个种群。比较野生鼠种群和亚种之间的图谱揭示了几个主题。首先，我们报告了在亚种和种群之间弱的精细和广泛的重组图谱保守性，遗传分化不能清楚地预测重组图谱的分化。其次，大多数热点是一个种群所特有的，这一结果与调查种群之间 Prdm9 等位基因的最小共享一致。最后，通过对比 X 染色体和常染色体上的总热点活性，我们发现了重组中性别二态性程度和方向的种群特异性差异的证据。总体而言，我们的研究结果阐明了 M. musculus 广泛和精细的重组景观的可变性，并强调了 Prdm9 等位基因变异在野生鼠种群中的功能影响。
