The genomic impact of historical hybridization with massive mitochondrial DNA introgression

Background: The extent to which selection determines interspecific patterns of genetic exchanges enlightens the role of adaptation in evolution and speciation. Often reported extensive interspecific introgression could be selection-driven, but also result from demographic processes, especially in cases of invasive species replacements, which can promote introgression at their front. Because invasion and selective sweeps similarly mold variation, population genetics evidence for selection can only be gathered in an explicit demographic framework. The Iberian hare, Lepus granatensis, displays in its northern range extensive mitochondrial DNA introgression from L. timidus, an arctic/boreal species that it replaced locally after the last glacial maximum. We use whole-genome sequencing to infer geographic and genomic patterns of nuclear introgression and fit a neutral model of species replacement with hybridization, allowing us to evaluate how selection influenced introgression genome-wide, including for mtDNA. Results: Although the average nuclear and mtDNA introgression patterns are strongly contrasted, they fit a single neutral model of post-glacial invasive replacement of timidus by granatensis. Outliers of elevated introgression include several genes related to immunity, spermatogenesis, and mitochondrial metabolism. Introgression is reduced on the X-chromosome and in low recombining regions. Conclusion: General nuclear and mtDNA patterns of introgression can be explained by purely demographic processes. Hybrid incompatibilities and interplay between selection and recombination locally modulate levels of nuclear introgression. Selection promoted introgression of some genes involved in conflicts, either interspecific (parasites) or possibly cytonuclear. In the latter case, nuclear introgression could mitigate the potential negative effects of alien mtDNA on mitochondrial metabolism and male-specific traits. Methods Hare (Lepus) pseudo-reference genome built through iterative mapping of sequencing reads from Lepus timidus, Lepus granatensis and Lepus americanus on the European rabbit (Oryctolagus cuniculus) genome template (available from ftp://ftp.ensembl.org/pub/release-80/fasta/oryctolagus_cuniculus/dna/).背景：选择作用对种间遗传交流模式的决定程度，有助于阐明适应在进化与物种形成过程中的角色。已有研究频繁报道的广泛种间基因渐渗（introgression）现象，既可能由选择驱动，也可由种群统计过程（demographic processes）导致——在入侵性物种替代场景中尤为如此，这类过程会在物种扩张前沿促进基因渐渗。由于物种入侵与选择性清除（selective sweep）对遗传变异的塑造模式相似，因此要获取支持选择作用的群体遗传学证据，必须依托明确的种群统计框架。伊比利亚兔（Lepus granatensis）在其分布北缘区域，存在大量来自北极/北方物种雪兔（Lepus timidus）的线粒体DNA（mtDNA）渐渗，后者在末次冰盛期后被伊比利亚兔在局部区域替代。本研究通过全基因组测序，推断核基因渐渗的地理与基因组模式，并拟合了带有杂交过程的物种替代中性模型，以此评估选择作用在全基因组范围内（包括线粒体基因组）对基因渐渗的影响。 结果：尽管核基因组与线粒体DNA的平均渐渗模式存在显著差异，但二者均符合“末次冰期后伊比利亚兔入侵替代雪兔”的单一中性模型。基因渐渗水平异常升高的位点，涉及多个与免疫、精子发生及线粒体代谢相关的基因。X染色体与低重组区域的基因渐渗水平则有所降低。 结论：种间基因渐渗的整体核基因组与线粒体DNA模式，可仅通过种群统计过程得到解释。杂交不相容性以及选择与重组之间的局部互作，会对核基因渐渗水平产生调控作用。选择作用促进了部分参与冲突相关过程的基因的渐渗，这类冲突包括种间冲突（如与寄生虫的互作）或可能的核质互作（cytonuclear）冲突。在后一种场景中，核基因渐渗可缓解外源线粒体DNA对线粒体代谢及雄性特异性性状的潜在负面影响。 方法：本研究以欧洲兔（Oryctolagus cuniculus）基因组（可从ftp://ftp.ensembl.org/pub/release-80/fasta/oryctolagus_cuniculus/dna/获取）作为参考模板，通过将雪兔（Lepus timidus）、伊比利亚兔（Lepus granatensis）与美洲兔（Lepus americanus）的测序读段进行迭代比对，构建兔属（Lepus）假参考基因组。