New Methods for Inferring the Distribution of Fitness Effects for INDELs and SNPs.
New Methods for Inferring the Distribution of Fitness Effects for INDELs and SNPs.
复制标题
DOI：
10.1093/molbev/msy054
复制
发表时间：
2018-06-01
影响因子：
10.7
通讯作者：
Zeng K
中科院分区：
文献类型：
--
作者：
Barton HJ;Zeng K
小插入和缺失（INDEL；≤50bp）是继单核苷酸多态性（SNP）之后最常见的变异类型。然而，与 SNP 相比，我们对新 INDEL 突变的适应度效应 (DFE) 分布以及适应性 INDEL 替换的普遍程度知之甚少。研究 INDEL 一直很困难，部分原因是识别这些地点的祖先状态很容易出错，而且错误识别可能会导致对选择强度的估计出现严重偏差。为了解决这些问题，我们开发了新的最大似然方法，该方法使用多态性数据同时估计 DFE、突变率和误识别率。这些方法适用于 INDEL 和 SNP。模拟表明它们可以提供高度准确的结果。我们将这些方法应用于果蝇的 INDEL 多态性数据集。我们发现蛋白质编码区多态性 INDEL 的 DFE 是双峰的，其中的变体要么几乎是中性的，要么是强烈有害的。根据 DFE，我们估计黑腹果蝇谱系中发生的 INDEL 替换中有 71.5-83.7% 是通过正选择固定的，这与非同义位点的适应性替换的流行程度相当。新方法已在软件包 anavar 中实现。
Small insertions and deletions (INDELs; ≤50 bp) are the most common type of variability after single nucleotide polymorphism (SNP). However, compared with SNPs, we know little about the distribution of fitness effects (DFE) of new INDEL mutations and how prevalent adaptive INDEL substitutions are. Studying INDELs has been difficult partly because identifying ancestral states at these sites is error-prone and misidentification can lead to severely biased estimates of the strength of selection. To solve these problems, we develop new maximum likelihood methods, which use polymorphism data to simultaneously estimate the DFE, the mutation rate, and the misidentification rate. These methods are applicable to both INDELs and SNPs. Simulations show that they can provide highly accurate results. We applied the methods to an INDEL polymorphism data set in Drosophila melanogaster. We found that the DFE for polymorphic INDELs in protein-coding regions is bimodal, with the variants being either nearly neutral or strongly deleterious. Based on the DFE, we estimated that 71.5–83.7% of the INDEL substitutions that took place along the D. melanogaster lineage were fixed by positive selection, which is comparable with the prevalence of adaptive substitutions at nonsynonymous sites. The new methods have been implemented in the software package anavar.
登录
查看更多内容
密码子偏倚选择强度随时间的变化导致果蝇碱基组成进化模式的对比。
影响因子：
3.3
作者：
Jackson BC;Campos JL;Haddrill PR;Charlesworth B;Zeng K
通讯作者：
Zeng K
影响因子：
3.3
作者：
Leushkin, Evgeny V.;Bazykin, Georgii A.
通讯作者：
Bazykin, Georgii A.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.3
作者：
Leushkin EV;Bazykin GA;Kondrashov AS
通讯作者：
Kondrashov AS
影响因子：
3.3
作者：
Kim BY;Huber CD;Lohmueller KE
通讯作者：
Lohmueller KE