Evolution of Homologous Recombination Mechanisms

摘要 同源重组亲本染色体之间的遗传信息， 多样性和推动进化。重组主要发生在重组热点， 基因组区域，其中重组频率超过相邻区域中的频率高达3 数量级。在某些物种中，热点机会性地定位于具有开放染色质的区域 在一些实施方案中，启动子可以是启动子、增强子和CpG岛。在其他人，包括人类和小鼠， 被PRDM9蛋白质引导远离这些功能元件，保护它们免受诱变作用 重组。Prdm9基因的缺失导致热点从PRDM9结合位点重新定位回 启动子，导致小鼠和大鼠的不育或生育能力低下，但似乎不是在人类。这意味着 功能基因组元件中重组诱导的突变将传递给后代。此外，委员会认为， 由于重组热点的位置在Prdm9突变体中发生了显著变化， 连锁不平衡将被打破，导致新的等位基因组合。因此，调查 Prdm9在通过进化而自然丢失Prdm9的物种中丢失的后果特别令人感兴趣。 在这项研究中，我们将在三个失去典型Prdm 9的物种中绘制重组热点，并检查三个 特定的机制，可以定义重组景观在这样的物种。

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.