Repeated Adaptive Introgression at a Gene under Multiallelic Balancing Selection

Recently diverged species typically have incomplete reproductive barriers, allowing introgression of genetic material from one species into the genomic background of the other. The role of natural selection in preventing or promoting introgression remains contentious. Because of genomic co-adaptation, some chromosomal fragments are expected to be selected against in the new background and resist introgression. In contrast, natural selection should favor introgression for alleles at genes evolving under multi-allelic balancing selection, such as the MHC in vertebrates, disease resistance, or self-incompatibility genes in plants. Here, we test the prediction that negative, frequency-dependent selection on alleles at the multi-allelic gene controlling pistil self-incompatibility specificity in two closely related species, Arabidopsis halleri and A. lyrata, caused introgression at this locus at a higher rate than the genomic background. Polymorphism at this gene is largely shared, and we have identified 18 pairs of S-alleles that are only slightly divergent between the two species. For these pairs of S-alleles, divergence at four-fold degenerate sites (K = 0.0193) is about four times lower than the genomic background (K = 0.0743). We demonstrate that this difference cannot be explained by differences in effective population size between the two types of loci. Rather, our data are most consistent with a five-fold increase of introgression rates for S-alleles as compared to the genomic background, making this study the first documented example of adaptive introgression facilitated by balancing selection. We suggest that this process plays an important role in the maintenance of high allelic diversity and divergence at the S-locus in flowering plant families. Because genes under balancing selection are expected to be among the last to stop introgressing, their comparison in closely related species provides a lower-bound estimate of the time since the species stopped forming fertile hybrids, thereby complementing the average portrait of divergence between species provided by genomic data.新近分化的物种通常存在不完全的生殖屏障，使得遗传物质可从一个物种渐渗进入另一物种的基因组背景。自然选择在阻碍或是促进基因渐渗过程中所扮演的角色，至今仍存在争议。由于基因组共适应的存在，部分染色体片段在新的基因组背景中会遭到负选择，进而抵抗渐渗。与之相反，对于经历多等位基因平衡选择的基因而言，自然选择应当会促进其等位基因的渐渗——例如脊椎动物的主要组织相容性复合体（MHC, Major Histocompatibility Complex）、抗病基因，以及植物的自交不亲和基因。本研究针对如下预测展开验证：在两个近缘物种——高山拟南芥（Arabidopsis halleri）与 lyrata拟南芥（A. lyrata）中，控制花柱自交不亲和特异性的多等位基因位点上，等位基因所承受的负频率依赖选择，使得该位点的渐渗速率高于基因组整体背景。该基因位点的多态性在两个物种间高度共享，我们已鉴定出18对S等位基因（S-alleles），二者在物种间仅存在极细微的分化。针对这18对S等位基因，其四倍简并位点（four-fold degenerate sites）的分化水平（K=0.0193）仅约为基因组背景水平（K=0.0743）的四分之一。我们证实，这一差异无法通过两类位点间有效种群大小（effective population size）的差异来解释。与之相反，我们的数据与“S等位基因的渐渗速率较基因组背景提升五倍”这一结论最为吻合，本研究也因此成为首个由平衡选择介导的适应性渐渗（adaptive introgression）的实证案例。我们推测，这一过程在显花植物类群的S位点（S-locus）维持高等位基因多样性与分化水平的过程中发挥了重要作用。由于经历平衡选择的基因被认为是最晚停止渐渗的类群之一，对近缘物种中这类基因的比较分析，可以为“物种停止形成可育杂种的时间”提供下限估计，从而补充基因组数据所描绘的物种间分化的一般图景。