Bioinformatics and Systems Biology Program, University of California, San Diego, California 92093.
Genetics. 2013 Sep;195(1):181-93. doi: 10.1534/genetics.113.152587. Epub 2013 Jun 14.
Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Many tests have been proposed to identify the genomic signatures of natural selection by quantifying the skew in the site frequency spectrum (SFS) under selection relative to neutrality. We build upon recent work that connects many of these tests under a common framework, by describing how selective sweeps affect the scaled SFS. We show that the specific skew depends on many attributes of the sweep, including the selection coefficient and the time under selection. Using supervised learning on extensive simulated data, we characterize the features of the scaled SFS that best separate different types of selective sweeps from neutrality. We develop a test, SFselect, that consistently outperforms many existing tests over a wide range of selective sweeps. We apply SFselect to polymorphism data from a laboratory evolution experiment of Drosophila melanogaster adapted to hypoxia and identify loci that strengthen the role of the Notch pathway in hypoxia tolerance, but were missed by previous approaches. We further apply our test to human data and identify regions that are in agreement with earlier studies, as well as many novel regions.
遗传适应外部刺激是通过突变和选择的共同作用发生的。遗传学中的一个核心问题是确定对特定选择压力有反应的基因座。已经提出了许多测试方法来通过量化选择相对于中性时的位点频率谱（SFS）的倾斜来识别自然选择的基因组特征。我们通过描述选择清除如何影响缩放的 SFS，在一个共同的框架下建立了许多这些测试的联系。我们表明，特定的倾斜取决于清除的许多属性，包括选择系数和选择时间。通过对大量模拟数据进行有监督学习，我们描述了最佳分离不同类型的选择清除与中性的缩放 SFS 的特征。我们开发了一种测试方法 SFselect，该方法在广泛的选择清除范围内始终优于许多现有的测试。我们将 SFselect 应用于适应低氧的黑腹果蝇实验室进化实验的多态性数据，鉴定出了 Notch 途径在低氧耐受性中起作用的基因座，但之前的方法没有发现这些基因座。我们进一步将我们的测试应用于人类数据，并确定了与早期研究一致的区域，以及许多新的区域。
