Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, UK.
Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, UK.
Curr Biol. 2020 Jan 6;30(1):94-100.e3. doi: 10.1016/j.cub.2019.10.047. Epub 2019 Dec 19.
The amount of DNA sequence variability in a genomic region is often positively correlated with its rate of crossing over (CO) [1-3]. This pattern is caused by selection acting on linked sites, which reduces genetic variability and biases the frequency distribution of segregating variants toward more rare variants than are expected without selection (skew). These effects may involve the spread of beneficial mutations (selective sweeps [SSWs]), the elimination of deleterious mutations (background selection [BGS]), or both, and are expected to be stronger with lower CO rates [1-3]. However, in a recent study of human populations, the skew was reduced in the lowest CO regions compared with regions with somewhat higher CO rates [4]. A low skew in very low CO regions, compared with theoretical predictions, is seen in the population genomic studies of Drosophila simulans described here and in other Drosophila species. Here, we propose an explanation for lower than expected skew in low CO regions, and validate it using computer simulations; explanations for higher skew with higher CO rates, as in D. simulans, will be explored elsewhere. Partially recessive, linked deleterious mutations can increase neutral variability when the product of the effective population size (N) and the selection coefficient against homozygous carriers of mutations (s) is ≤1, i.e., there is associative overdominance (AOD) rather than BGS [5]. AOD can operate in low CO regions, producing a lower skew than in its absence. This opens up a new perspective on how selection affects patterns of variability at linked sites.
基因组区域中的 DNA 序列变异量通常与交叉率 (CO) 呈正相关[1-3]。这种模式是由连锁位点上的选择作用引起的，选择作用降低了遗传变异，并使分离变异的频率分布偏向于比没有选择时更罕见的变异（偏斜）。这些效应可能涉及有益突变的扩散（选择清除 [SSWs]）、有害突变的消除（背景选择 [BGS]）或两者兼而有之，并且在 CO 率较低时预期更强[1-3]。然而，在最近对人类群体的研究中，与 CO 率略高的区域相比，CO 率最低的区域的偏斜度降低了[4]。与理论预测相比，在本文和其他果蝇物种的种群基因组研究中，在 CO 非常低的区域中观察到的偏斜度降低。在这里，我们提出了一个解释，即 CO 低的区域中预期的偏斜度较低，并使用计算机模拟对其进行了验证；对于 CO 率较高的区域（如 D. simulans 中的 CO 率较高）的更高偏斜度，将在其他地方进行探讨。当有效种群大小 (N) 与针对突变纯合载体的选择系数 (s) 的乘积 ≤1 时，部分隐性、连锁有害突变可以增加中性变异，即存在关联超显性（AOD）而不是 BGS[5]。AOD 可以在 CO 较低的区域中起作用，产生的偏斜度低于没有 AOD 的情况。这为选择如何影响连锁位点的变异模式提供了一个新的视角。
