Background Selection Does Not Mimic the Patterns of Genetic Diversity Produced by Selective Sweeps
Background Selection Does Not Mimic the Patterns of Genetic Diversity Produced by Selective Sweeps
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DOI：
10.1534/genetics.120.303469
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发表时间：
2020-10-01
期刊：
影响因子：
3.3
通讯作者：
Schrider, Daniel R.
中科院分区：
文献类型：
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作者：
Schrider, Daniel R.
越来越明显的是，自然选择在塑造整个基因组的多样性模式方面发挥着重要作用。自然选择最常被研究的模式是正向选择和负向选择，分别指对衍生突变的定向选择和对衍生突变的定向选择。正选择可以导致搭便车事件，其中有益等位基因迅速取代群体中的所有其他等位基因，在所选位点周围产生多样性的谷，沿着等位基因频率的特征偏斜和连锁中性多态性之间的连锁不平衡。同样，负选择不仅减少了选定位点的变异，也减少了连锁位点的变异，这种现象称为背景选择（BGS）。因此，区分这两种力可能是困难的，并且人们可能期望检测搭便车的努力在受BGS影响的区域中产生过量的假阳性。在这里，我们通过模拟研究BGS和搭便车模型之间的相似性。首先，我们表明，BGS可能有点类似于搭便车在简单的情况下，在一个区域的负选择的限制两侧是大片的不受约束的网站，呼应以前的结果。然而，这种情况并不反映整个基因组中选定位点的实际空间排列。通过在更现实的BGS场景下进行正向模拟，对蛋白质编码和保守的非编码DNA在真实的基因组中的位置进行建模，我们发现BGS产生的变异的空间模式很少模仿搭便车事件。事实上，BGS并不比中立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统计学历史。这些结果表明，适当设计的扫描搭便车不需要考虑BGS的假阳性率的影响。然而，我们确实发现证据表明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。
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 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 andDrosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider BGS'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.