Estimating the strength of selective sweeps from deep population diversity data.
Estimating the strength of selective sweeps from deep population diversity data.
复制标题
从深度种群多样性数据中估算选择性扫描的强度。
DOI：
10.1534/genetics.112.138461
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发表时间：
2012-06
期刊：
影响因子：
3.3
通讯作者：
Neher RA
中科院分区：
文献类型：
--
作者：
Messer PW;Neher RA
选择性扫描通常与适应位点周围遗传多样性的局部减少有关。然而，选择性扫描也可以快速携带中性突变到可观察到的群体频率，如果它们在扫描中出现得较早，并与适应性等位基因搭便车。我们表明，突变和搭便车的指数扩增之间的相互作用导致了所产生的新单倍型变异的特征频谱，该特征频谱仅取决于突变率和扫描选择系数的比率。在此结果的基础上，我们开发了驱动扫描的选择系数的估计。由于该估计器利用了扫描过程中突变产生的新变异，因此它不依赖于先前存在的变异，也可以应用于缺乏重组的位点。与从适应位点周围遗传多样性下降的大小推断选择系数的标准方法相比，我们的估计方法需要更短的序列，但在高种群深度取样以捕获低频变异；给定这样的数据，它始终优于标准方法。我们分析和数值研究了随机遗传漂变导致的扫描模式随时间衰减对估计器精度的影响，并讨论了重组、软扫描和人口统计学的潜在影响。作为其使用的一个例子，我们将我们的估计器应用于人类免疫缺陷病毒种群的深度测序数据。
Selective sweeps are typically associated with a local reduction of genetic diversity around the adaptive site. However, selective sweeps can also quickly carry neutral mutations to observable population frequencies if they arise early in a sweep and hitchhike with the adaptive allele. We show that the interplay between mutation and exponential amplification through hitchhiking results in a characteristic frequency spectrum of the resulting novel haplotype variation that depends only on the ratio of the mutation rate and the selection coefficient of the sweep. On the basis of this result, we develop an estimator for the selection coefficient driving a sweep. Since this estimator utilizes the novel variation arising from mutations during a sweep, it does not rely on preexisting variation and can also be applied to loci that lack recombination. Compared with standard approaches that infer selection coefficients from the size of dips in genetic diversity around the adaptive site, our estimator requires much shorter sequences but sampled at high population depth to capture low-frequency variants; given such data, it consistently outperforms standard approaches. We investigate analytically and numerically how the accuracy of our estimator is affected by the decay of the sweep pattern over time as a consequence of random genetic drift and discuss potential effects of recombination, soft sweeps, and demography. As an example for its use, we apply our estimator to deep sequencing data from human immunodeficiency virus populations.