Garud Nandita R, Messer Philipp W, Buzbas Erkan O, Petrov Dmitri A
Department of Genetics, Stanford University, Stanford, California, United States of America; Department of Biology, Stanford University, Stanford, California, United States of America.
Department of Biology, Stanford University, Stanford, California, United States of America; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America.
PLoS Genet. 2015 Feb 23;11(2):e1005004. doi: 10.1371/journal.pgen.1005004. eCollection 2015 Feb.
Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.
在大群体中，由现有遗传变异或反复出现的新生突变导致的适应性变化通常会产生软选择清除而非硬选择清除。与硬选择清除不同，硬选择清除是单个适应性单倍型在群体中频率升高，而在软选择清除中，多个适应性单倍型会同时在群体中扩散，在适应性位点附近产生不同的遗传变异模式。当前的统计方法是专门设计用于检测硬选择清除的，大多数方法缺乏检测软选择清除的能力。这对于研究诸如黑腹果蝇这类物种的适应性来说尤其不利，在黑腹果蝇中，所有三个已确认的近期适应性案例都导致了软选择清除，而且有证据表明，即使适应性需要在一个基因座的特定单一位点发生突变，与近期强烈适应性相关的有效群体大小也足以产生软选择清除。在此，我们基于单倍型纯合度（H12）的测量开发了一种统计检验方法，该方法能够以相似的效力检测硬选择清除和软选择清除。我们使用H12在来自果蝇遗传参考面板（DGRP）的大量全基因组测序黑腹果蝇菌株群体样本中识别出多个经历了近期强烈适应性变化的基因组区域。对前50个候选区域的直观检查表明，在所有案例中都有多个高频单倍型存在，这与软选择清除的特征一致。我们进一步开发了第二个单倍型纯合度统计量（H2/H1），它与H12相结合，能够区分硬选择清除和软选择清除。令人惊讶的是，我们发现所有前50个峰值的H12和H2/H1值更容易由软选择清除而非硬选择清除产生。我们讨论了这些结果对黑腹果蝇以及普查群体规模较大的物种适应性研究的意义。
