Variation and selection on codon usage bias across an entire subphylum

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.

Using GC content to compare recombination patterns on the sex chromosomes and autosomes of the guppy,Poecilia reticulata, and its close outgroup species

“…A less clear pattern is expected in coding regions than for intronic GC, given that selection 273 on codon usage may affect such sites (Labella, et al 2019), and also because GC content is 274 generally higher in coding regions than introns, as reviewed by Beauclair (2019), making 275 increases less likely to be detected. Nevertheless, GC in third codon positions (GC3 values) 276 also show significant increases at the ends of many guppy chromosomes.…”

The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder

“…Paradoxically, this can make more exquisitely adapted species have lower rather than higher species-level CAI scores. CAI and RSCUs have been inappropriately used as metrics of codon adaptation across species in a handful of publications, adding to the confusion (Jansen et al 2003; Labella et al 2019).…”

Quantifying shifts in natural selection on codon usage between protein regions: A population genetics approach

“…Patterns of codon usage bias (CUB), or the non-uniform usage of synonymous codons, vary both within and across species (Drummond and Wilke, 2009;Hershberg and Petrov, 2008; Plotkin and Kudla, 2011;Labella et al, 2019). Although non-adaptive evolutionary forces, such as mutation bias, genetic drift, and recombination, are well-known to shape codon usage patterns, natural selection also plays a significant role.…”