Oryctolagus cuniculus Targeted Locus (Loci)

The analysis of introgression of genomic regions between divergent populations provides an excellent opportunity to determine the genetic basis of reproductive isolation during the early stages of speciation. However, hybridization and subsequent gene flow must be relatively common in order to localize individual loci that resist introgression. In this study, we used next-generation sequencing to study genome-wide patterns of genetic differentiation between two hybridizing subspecies of rabbits (O cuniculus algirus and O. c. cuniculus) that are known to undergo high rates of gene exchange. Our primary objective was to identify specific genes or genomic regions that have resisted introgression and are likely to confer reproductive barriers in natural conditions. On the basis of 326,000 polymorphisms, we found low to moderate overall levels of differentiation between subspecies, and fewer than 200 genomic regions dispersed throughout the genome showing high differentiation consistent with a signature of reduced gene flow. Most differentiated regions were smaller than 200 Kb and contained very few genes. Remarkably, 30 regions were each found to contain a single gene, facilitating the identification of candidate genes underlying reproductive isolation. This gene-level resolution yielded several insights into the genetic basis and architecture of reproductive isolation in rabbits. Regions of high differentiation were enriched on the X-chromosome and near centromeres. Genes lying within differentiated regions were often associated with transcription and epigenetic activities, including chromatin organization, regulation of transcription, and DNA binding. Overall, our results from a naturally hybridizing system share important commonalities with hybrid incompatibility genes identified using laboratory crosses in mice and flies, highlighting general mechanisms underlying the maintenance of reproductive barriers.

对不同类群间基因组区域渐渗（introgression）的分析，为解析物种形成早期阶段生殖隔离的遗传基础提供了极佳契机。不过，要定位到具有渐渗抗性的单个基因座，杂交与后续的基因流需相对频繁。本研究利用下一代测序（next-generation sequencing）技术，对两个已知存在高频基因交流的杂交兔亚种（O cuniculus algirus 和 O. c. cuniculus）的全基因组遗传分化模式展开分析。本研究的核心目标是鉴定出在自然条件下具有渐渗抗性、且可能参与构建生殖隔离屏障的特定基因或基因组区域。基于326,000个多态性位点的分析，我们发现两个亚种间的整体遗传分化水平处于低到中等程度，且全基因组范围内仅存在不足200个呈高度分化的基因组区域，这些区域的分化特征与基因流受限的分子印记相符。多数分化区域的长度小于200千碱基对（Kb），且仅包含极少的基因。值得注意的是，其中30个分化区域各仅包含一个基因，这为鉴定生殖隔离相关的候选基因提供了便利。这种基因水平的分辨率为解析家兔生殖隔离的遗传基础与调控架构提供了多维度认知。高度分化的区域在X染色体（X-chromosome）及着丝粒（centromere）附近呈现富集现象。位于分化区域内的基因通常与转录及表观遗传调控活动相关，包括染色质组织、转录调控以及DNA结合功能。总体而言，本研究基于自然杂交系统获得的结果，与通过实验室杂交在小鼠和果蝇中鉴定出的杂交不亲和基因存在重要共性，这为解析维持生殖隔离的通用分子机制提供了新的视角。