非重组种群选择性掠夺期间的遗传多样性

Sachin Kaushik, Kavita Jain, Parul Johri
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摘要

有益、中性或有害突变在种群中的传播所产生的选择性突变,塑造了相关中性位点的遗传变异模式。虽然在理解重组种群中选择性横扫的基因组特征方面取得了许多理论、计算和统计方面的进展,但对很少/没有重组的种群的了解却少得多。我们提出了一个基于扩散理论的数学框架,用于获取中度或高度有益突变固定后和固定期间链接中性位点的位点频谱(SFS)。我们发现,当发生单次硬扫描时,低衍生等位基因频率(x)的位点频谱衰减为 1/x,类似于平衡状态下的中性位点频谱,而当衍生等位基因频率较高时,则遵循 1/x2 的幂律。这些幂律是普遍的,因为它们与显性系数和近交系数无关,也是横扫过程中 SFS 的特征。此外,我们还发现,SFS 从 1/x 转向 1/x2 的衍生等位基因频率与选择强度成反比:因此,在强选择下,大多数等位基因频率的 SFS 遵循 1/x2 依赖性,类似于一个快速扩张的中性种群。当克隆干扰普遍存在时,固定后的 SFS 会立即变为 U 型,并能更好地用所选位点的平衡 SFS 来解释。我们的研究结果对于开发统计方法以推断无性种群、缺乏重组的基因组区域以及克隆传播的肿瘤种群中近期选择性扫描的时间和强度非常重要。
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Genetic diversity during selective sweeps in non-recombining populations
Selective sweeps, resulting from the spread of beneficial, neutral, or deleterious mutations through a population, shape patterns of genetic variation at linked neutral sites. While many theoretical, computational, and statistical advances have been made in understanding the genomic signatures of selective sweeps in recombining populations, substantially less is understood in populations with little/no recombination. We present a mathematical framework based on diffusion theory for obtaining the site frequency spectrum (SFS) at linked neutral sites immediately post and during the fixation of moderately or strongly beneficial mutations. We find that when a single hard sweep occurs, the SFS decays as 1/x for low derived allele frequencies (x), similar to the neutral SFS at equilibrium, whereas at higher derived allele frequencies, it follows a 1/x2 power law. These power laws are universal in the sense that they are independent of the dominance and inbreeding coefficient, and also characterize the SFS during the sweep. Additionally, we find that the derived allele frequency where the SFS shifts from the 1/x to 1/x2 law, is inversely proportional to the selection strength: thus under strong selection, the SFS follows the 1/x2 dependence for most allele frequencies, resembling a rapidly expanding neutral population. When clonal interference is pervasive, the SFS immediately post-fixation becomes U-shaped and is better explained by the equilibrium SFS of selected sites. Our results will be important in developing statistical methods to infer the timing and strength of recent selective sweeps in asexual populations, genomic regions that lack recombination, and clonally propagating tumor populations.
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