New Methods for Inferring the Distribution of Fitness Effects for INDELs and SNPs

被引:22
作者
Barton, Henry J. [1 ]
Zeng, Kai [1 ]
机构
[1] Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England
基金
英国自然环境研究理事会;
关键词
distribution of fitness effects; insertions and deletions; single nucleotide polymorphism; polarisation error; BIASED GENE CONVERSION; DROSOPHILA-MELANOGASTER; MUTATION-RATES; DELETERIOUS MUTATIONS; NATURAL-SELECTION; DNA LOSS; EVOLUTION; GENOME; POLYMORPHISM; SEQUENCES;
D O I
10.1093/molbev/msy054
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small insertions and deletions (INDELs; <S8 6p) 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.
引用
收藏
页码:1536 / 1546
页数:11
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