Linked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection [BGS]) [], creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD) [, ], due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao and Charlesworth [] identified the conditions under which AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance [], i.e., a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low-recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans [], the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 22 such regions in the human genome consistent with multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low-recombination regions of many species.

中文翻译：

---

从背景选择到关联优势的转变促进了低重组区域的多样性

连锁选择是遗传多样性的主要驱动力。针对有害突变的选择消除了相关的中性多样性（背景选择[BGS]）[]，从而在重组率和遗传多样性之间形成正相关。然而，针对隐性变异的纯化选择也可能导致关联过度显性（AOD）[,]，因为在相连的中性位点上存在明显的杂合子优势，反对 BGS 造成的中性多样性的丧失。 Chao 和 Charlesworth [] 确定了在单基因座模型中 AOD 应优于 BGS 的条件，并提出如果多个连锁的有害变异共分离，AOD 的作用可能会变得更强。我们提出了一个模型，描述多位点动力学如何以及在什么条件下可以放大 AOD 的效果。我们推导了由于伪超显性而从 BGS 过渡到 AOD 的条件，即一种平衡选择的形式，可维持互补的有害单倍型，从而掩盖隐性有害突变的影响。模拟证实了这些发现，并表明多位点 AOD 可以比以前认为的更强烈地增加低重组区域的多样性。虽然已知 BGS 可以驱动人类全基因组多样性，但在重组极低的区域观察到遗传多样性的复苏表明了 AOD。我们在人类基因组中鉴定出 22 个与多位点 AOD 一致的此类区域。我们的结果表明，AOD 可能在许多物种低重组区域的进化中发挥重要作用。