It is increasingly evident that natural selection plays a prominent role in shaping patterns of diversity across the genome. The most commonly studied modes of natural selection are positive selection and negative selection, which refer to directional selection for and against derived mutations, respectively. Positive selection can result in hitchhiking events, in which a beneficial allele rapidly replaces all others in the population, creating a valley of diversity around the selected site along with characteristic skews in allele frequencies and linkage disequilibrium (LD) among linked neutral polymorphisms. Similarly, negative selection reduces variation not only at selected sites but also at linked sites-a phenomenon called background selection (BGS). Thus, discriminating between these two forces may be difficult, and one might expect efforts to detect hitchhiking to produce an excess of false positives in regions affected by BGS. Here, we examine the similarity between BGS and hitchhiking models via simulation. First, we show that BGS may somewhat resemble hitchhiking in simplistic scenarios in which a region constrained by negative selection is flanked by large stretches of unconstrained sites, echoing previous results. However, this scenario does not mirror the actual spatial arrangement of selected sites across the genome. By performing forward simulations under more realistic scenarios of BGS, modeling the locations of protein-coding and conserved noncoding DNA in real genomes, we show that the spatial patterns of variation produced by BGS rarely mimic those of hitchhiking events. Indeed, BGS is not substantially more likely than neutrality to produce false signatures of hitchhiking. This holds for simulations modeled after both humans and Drosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider background selection's impact on false positive rates. However, we do find evidence that BGS increases the false negative rate for hitchhiking-an observation that demands further investigation.

中文翻译：

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背景选择不会模仿选择性扫描产生的遗传多样性模式。

越来越明显的是，自然选择在塑造整个基因组多样性模式方面发挥着重要作用。最常研究的自然选择模式是正选择和负选择，它们分别指针对和反对衍生突变的定向选择。正选择可能导致搭便车事件，其中有益的等位基因迅速取代群体中的所有其他等位基因，在选定位点周围形成多样性谷，以及等位基因频率的特征倾斜和连锁中性多态性之间的连锁不平衡（LD）。同样，负选择不仅减少了选定位点的变异，而且还减少了链接位点的变异，这种现象称为背景选择（BGS）。因此，区分这两种力量可能很困难，并且人们可能期望检测搭便车行为的努力会在受 BGS 影响的地区产生过多的误报。在这里，我们通过模拟检查 BGS 和搭便车模型之间的相似性。首先，我们表明 BGS 可能有点类似于简单场景中的搭便车，其中受负选择约束的区域两侧是大片不受约束的位点，这与之前的结果相呼应。然而，这种情况并没有反映整个基因组中选定位点的实际空间排列。通过在更真实的 BGS 场景下进行正向模拟，对真实基因组中蛋白质编码和保守非编码 DNA 的位置进行建模，我们表明 BGS 产生的变异的空间模式很少模仿搭便车事件的空间模式。事实上，BGS 并不比中立性更有可能产生搭便车的虚假签名。这适用于以人类和果蝇为模型的模拟，以及几种不同的人口历史。这些结果表明，适当设计的搭便车扫描不需要考虑背景选择对误报率的影响。然而，我们确实发现有证据表明 BGS 增加了搭便车的假阴性率，这一观察结果需要进一步调查。