Codon Usage Bias in Animals: Disentangling the Effects of Natural Selection, Effective Population Size, and GC-Biased Gene Conversion.

Nicolas Galtier,Emeric Figuet,Sylvain Glémin,Laurent Duret,Marjolaine Rousselle,Camille Roux,Jonathan Romiguier,Nicolas Bierne,Nadia Singh

doi:10.1093/molbev/msy015

Abstract

Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased gene conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased gene conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased gene conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.

Highlights

The reasons why synonymous codons do not occur at equal frequencies in protein coding sequences have been puzzling molecular evolutionary researchers for decades (Duret 2002; Hershberg and Petrov 2008)
In Escherichia coli and Saccharomyces cerevisiae, for instance, the codons most commonly observed in highly expressed genes match the most abundant tRNAs in the cell (Ikemura 1985), strongly suggesting that codon usage and tRNA content have coevolved in a way that optimizes translation— the term “translational selection.”
We focused our analysis of translational selection on GC-conservative pairs of synonymous codons—that is, codons differing by a G$C or an A$T substitution—and separately analyzed the effect of GC-biased gene conversion (gBGC)

Summary

Introduction

The reasons why synonymous codons do not occur at equal frequencies in protein coding sequences have been puzzling molecular evolutionary researchers for decades (Duret 2002; Hershberg and Petrov 2008). In Escherichia coli and Saccharomyces cerevisiae, for instance, the codons most commonly observed in highly expressed genes match the most abundant tRNAs in the cell (Ikemura 1985), strongly suggesting that codon usage and tRNA content have coevolved in a way that optimizes translation— the term “translational selection.”. These observations promoted codon usage bias as a textbook example of a weak selective pressure operating at molecular level, detectable from patterns of coding sequence variation, but difficult to apprehend experimentally. One question of interest is whether selection shapes codon usage in large organisms, such as animals, the same way as in microbes, despite their presumably smaller Ne

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