Inferring the distribution of selective effects from a time inhomogeneous model.

Amei Amei,Shilei Zhou,Francesc Calafell

doi:10.1371/journal.pone.0194709

Abstract

We have developed a Poisson random field model for estimating the distribution of selective effects of newly arisen nonsynonymous mutations that could be observed as polymorphism or divergence in samples of two related species under the assumption that the two species populations are not at mutation-selection-drift equilibrium. The model is applied to 91Drosophila genes by comparing levels of polymorphism in an African population of D. melanogaster with divergence to a reference strain of D. simulans. Based on the difference of gene expression level between testes and ovaries, the 91 genes were classified as 33 male-biased, 28 female-biased, and 30 sex-unbiased genes. Under a Bayesian framework, Markov chain Monte Carlo simulations are implemented to the model in which the distribution of selective effects is assumed to be Gaussian with a mean that may differ from one gene to the other to sample key parameters. Based on our estimates, the majority of newly-arisen nonsynonymous mutations that could contribute to polymorphism or divergence in Drosophila species are mildly deleterious with a mean scaled selection coefficient of -2.81, while almost 86% of the fixed differences between species are driven by positive selection. There are only 16.6% of the nonsynonymous mutations observed in sex-unbiased genes that are under positive selection in comparison to 30% of male-biased and 46% of female-biased genes that are beneficial. We also estimated that D. melanogaster and D. simulans may have diverged 1.72 million years ago.

Highlights

IntroductionComparison between silent (or synonymous) polymorphism with amino acid replacement (or nonsynonymous) polymorphism has served as a basis of inferring natural selection for more than 30 years [1]
Comparison between silent polymorphism with amino acid replacement polymorphism has served as a basis of inferring natural selection for more than 30 years [1]
At each locus, the silent and replacement mutation rates θs and θr were generated from two continuous uniform distributions with given ranges, the numbers of alignment sequences m and n were drawn from two discrete uniform distributions with certain ranges, and the selection coefficient γ was sampled from a normal distribution with mean γm and variance s2w, where γm was a random draw from a normal distribution with mean μγ and variance s2b

Summary

Introduction

Comparison between silent (or synonymous) polymorphism with amino acid replacement (or nonsynonymous) polymorphism has served as a basis of inferring natural selection for more than 30 years [1]. The original idea of comparison within one species [1, 2] has been extended by Hudson et al to comparing polymorphisms within species with fixed differences between species [3]. Given aligned DNA sequences from two closely related species, McDonald and Kreitman [4] proposed a statistical test of neutrality for a 2 × 2 contingency table whose four entries are total numbers of silent or replacement polymorphic sites within species and fixed differences between species (see [5,6,7,8,9,10,11,12,13]). Distribution of selective effects from a time inhomogeneous model these authors are articulated in the ‘author contributions’ section

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Conclusion