How reliable are empirical genomic scans for selective sweeps?
How reliable are empirical genomic scans for selective sweeps?
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DOI：
10.1101/gr.5105206
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发表时间：
2006-06-01
期刊：
影响因子：
7
通讯作者：
Przeworski, Molly
中科院分区：
文献类型：
--
作者：
Teshima, Kosuke M.;Coop, Graham;Przeworski, Molly
等位基因的有益替代塑造了连锁位点的遗传变异模式。因此，原则上，可以通过在多态性数据中寻找方向选择的签名来映射适应。在实践中，这种努力因需要准确描述物种的人口统计历史和积极选择的影响而受到阻碍。为了克服这些困难，研究人员越来越多地采用纯粹的经验方法，其中大量基因组区域根据多态性数据的摘要进行排序，并且具有极值的基因座被认为是正选择的可能目标。我们评估了“经验”方法的可靠性，重点关注对人类数据和玉米的应用。为此，我们考虑了在合理的人口统计环境中定向选择的合并模型，允许对长期变异和新突变进行选择。我们的模拟表明，虽然经验方法将识别出几个有趣的候选基因，但它们也会错过许多（在某些情况下）最感兴趣的基因座。权衡的程度取决于正选择的模式和人口的人口历史。具体来说，当定向选择涉及隐性而非共显性等位基因时，当它作用于先前中性的等位基因而不是新的等位基因时，以及当群体经历了群体瓶颈而不是保持恒定的规模时，错误发现率更高。这些结果的一个含义是，只要有益突变的属性（例如，显性系数）影响检测选择目标的能力，基因组扫描将产生有助于适应的不具代表性的基因座子集。
The beneficial substitution of an allele shapes patterns of genetic variation at linked sites. Thus, in principle, adaptations can be mapped by looking for the signature of directional selection in polymorphism data. In practice, such efforts are hampered by the need for an accurate characterization of the demographic history of the species and of the effects of positive selection. In an attempt to circumvent these difficulties, researchers are increasingly taking a purely empirical approach, in which a large number of genomic regions are ordered by summaries of the polymorphism data, and loci with extreme values are considered to be likely targets of positive selection. We evaluated the reliability of the '' empirical '' approach, focusing on applications to human data and to maize. To do so, we considered a coalescent model of directional selection in a sensible demographic setting, allowing for selection on standing variation as well as on a new mutation. Our simulations suggest that while empirical approaches will identify several interesting candidates, they will also miss many-in some cases, most-loci of interest. The extent of the trade-off depends on the mode of positive selection and the demographic history of the population. Specifically, the false-discovery rate is higher when directional selection involves a recessive rather than a co-dominant allele, when it acts on a previously neutral rather than a new allele, and when the population has experienced a population bottleneck rather than maintained a constant size. One implication of these results is that, insofar as attributes of the beneficial mutation ( e. g., the dominance coefficient) affect the power to detect targets of selection, genomic scans will yield an unrepresentative subset of loci that contribute to adaptations.