Variation and selection on codon usage bias across an entire subphylum.

Abigail L Labella,Chris Todd Hittinger,Antonis Rokas,Dana A Opulente,Jacob L Steenwyk,Gregory S Barsh

doi:10.1371/journal.pgen.1008304

Abstract

Variation in synonymous codon usage is abundant across multiple levels of organization: between codons of an amino acid, between genes in a genome, and between genomes of different species. It is now well understood that variation in synonymous codon usage is influenced by mutational bias coupled with both natural selection for translational efficiency and genetic drift, but how these processes shape patterns of codon usage bias across entire lineages remains unexplored. To address this question, we used a rich genomic data set of 327 species that covers nearly one third of the known biodiversity of the budding yeast subphylum Saccharomycotina. We found that, while genome-wide relative synonymous codon usage (RSCU) for all codons was highly correlated with the GC content of the third codon position (GC3), the usage of codons for the amino acids proline, arginine, and glycine was inconsistent with the neutral expectation where mutational bias coupled with genetic drift drive codon usage. Examination between genes’ effective numbers of codons and their GC3 contents in individual genomes revealed that nearly a quarter of genes (381,174/1,683,203; 23%), as well as most genomes (308/327; 94%), significantly deviate from the neutral expectation. Finally, by evaluating the imprint of translational selection on codon usage, measured as the degree to which genes’ adaptiveness to the tRNA pool were correlated with selective pressure, we show that translational selection is widespread in budding yeast genomes (264/327; 81%). These results suggest that the contribution of translational selection and drift to patterns of synonymous codon usage across budding yeasts varies across codons, genes, and genomes; whereas drift is the primary driver of global codon usage across the subphylum, the codon bias of large numbers of genes in the majority of genomes is influenced by translational selection.

Highlights

One of the first insights drawn from DNA sequence analyses was that synonymous codons are used both non-randomly and in taxon-specific patterns [1,2,3]
While genome-wide relative synonymous codon usage (RSCU) for all codons was highly correlated with the GC content of the third codon position (GC3), the usage of codons for the amino acids proline, arginine, and glycine was inconsistent with the neutral expectation where mutational bias coupled with genetic drift drive codon usage
These results suggest that the contribution of translational selection and drift to patterns of synonymous codon usage across budding yeasts varies across codons, genes, and genomes; whereas drift is the primary driver of global codon usage across the subphylum, the codon bias of large numbers of genes in the majority of genomes is influenced by translational selection

Summary

Introduction

One of the first insights drawn from DNA sequence analyses was that synonymous codons are used both non-randomly and in taxon-specific patterns [1,2,3]. Non-optimal codon usage has been associated with translation initiation [19], accurate protein folding [20,21,22], and signal recognition particle detection [23]. These molecular discoveries are complemented by a plethora of examples where specific synonymous substitutions have substantial fitness [24,25,26,27] and phenotypic effects in organisms across the tree of life, including Escherichia coli [28], Saccharomyces cerevisiae [29, 30], Drosophila melanogaster [31], and humans [32,33,34]. There is substantial evidence to suggest that codon usage bias of certain codons in certain species is under strong selection—often through translational mechanisms

Methods

Results

Conclusion