Evolution of Homologous Recombination Mechanisms

摘要 同源重组重组亲本染色体间的遗传信息 多样性和推动进化。复合主要发生在复合热点，狭窄的 重组频率超过邻近区域高达三倍的基因组区域 数量级。在一些物种中，热点机会性地定位于染色质开放的区域。 配置，如启动子、增强剂和CpG岛。在其他动物中，包括人类和老鼠，热点 被PRDM9蛋白从这些功能元件中转移出去，保护它们免受诱变效应 重组。Prdm9基因缺失导致热点从PRDM9结合位点移回 对启动子，导致小鼠和大鼠不育或不育，但对人类似乎不是。这意味着 重组诱导的功能性基因组元件突变将传递给后代。此外， 由于重组热点的位置在Prdm9突变体中发生了巨大的变化，因此 连锁不平衡将被打破，导致新的等位基因组合。因此，对这一事件的调查 通过进化自然失去Prdm9的物种的Prdm9丢失的后果特别令人感兴趣。 在这项研究中，我们将在三个失去经典Prdm9的物种中定位重组热点，并检查三个 可能定义这些物种中重组景观的特定机制。

ABSTRACT Homologous recombination reshuffles genetic information between parental chromosomes generating genetic diversity and driving evolution. Recombination predominantly occurs at recombination hotspots, the narrow genomic regions where recombination frequency exceeds the frequency in the adjacent areas by up to three orders of magnitude. In some species, hotspots localize opportunistically to the regions with open chromatin configuration, such as promoters, enhancers and CpG islands. In others, including humans and mice, hotspots are routed away from these functional elements by the PRDM9 protein, protecting them from mutagenic effects of recombination. Deletion of the Prdm9 gene results in relocation of hotspots from PRDM9 binding sites back to promoters, leading to sterility or subfertility in mice and rats, but seemingly not in humans. This means that recombination-induced mutations in functional genomic elements will be passed to progeny. Furthermore, since locations of recombination hotspots change dramatically in Prdm9 mutants, the established patterns of linkage disequilibrium will be broken, leading to novel allele combinations. Therefore, investigation of the consequences of the Prdm9 loss in species that naturally lost Prdm9 through evolution is of particular interest. In this study we will map recombination hotspots in three species that lost canonical Prdm9 and examine three specific mechanisms that may define recombination landscape in such species.