Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.
Centre for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China.
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4762-E4771. doi: 10.1073/pnas.1619434114. Epub 2017 May 30.
We used whole-genome resequencing data from a population of to investigate the causes of the negative correlation between the within-population synonymous nucleotide site diversity ( ) of a gene and its degree of divergence from related species at nonsynonymous nucleotide sites ( ). By using the estimated distributions of mutational effects on fitness at nonsynonymous and UTR sites, we predicted the effects of background selection at sites within a gene on and found that these could account for only part of the observed correlation between and We developed a model of the effects of selective sweeps that included gene conversion as well as crossing over. We used this model to estimate the average strength of selection on positively selected mutations in coding sequences and in UTRs, as well as the proportions of new mutations that are selectively advantageous. Genes with high levels of selective constraint on nonsynonymous sites were found to have lower strengths of positive selection and lower proportions of advantageous mutations than genes with low levels of constraint. Overall, background selection and selective sweeps within a typical gene reduce its synonymous diversity to ∼75% of its value in the absence of selection, with larger reductions for genes with high Gene conversion has a major effect on the estimates of the parameters of positive selection, such that the estimated strength of selection on favorable mutations is greatly reduced if it is ignored.
我们利用来自一个群体的全基因组重测序数据，研究了一个基因的种内同义核苷酸位点多样性（）与其在非同义核苷酸位点上与相关物种的分歧程度（）之间呈负相关的原因。通过使用对非同义及 UTR 位点上适应性突变效应的估计分布，我们预测了基因内背景选择对的影响，发现这些只能部分解释观察到的与之间的相关性。我们开发了一个包括基因转换和交叉的选择清除效应模型。我们使用该模型估计了编码序列和 UTR 中新正选择突变的平均强度以及有利突变的比例。与低约束水平的基因相比，具有高非同义约束水平的基因的正选择强度较低，有利突变的比例也较低。总的来说，在一个典型的基因中，背景选择和清除会将其同义多样性降低到没有选择时的约 75%，而高约束水平的基因的降低幅度更大。基因转换对正选择参数的估计有重大影响，如果忽略它，有利突变的选择强度的估计值将大大降低。
