Variation and selection on codon usage bias across an entire subphylum

PLoS Genet. 2019 Jul 31;15(7):e1008304. doi: 10.1371/journal.pgen.1008304. eCollection 2019 Jul.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bias
  • Codon Usage*
  • Genetic Variation
  • Genome, Fungal
  • Saccharomycetales / genetics*
  • Selection, Genetic

Grant support

This work was supported in part by the National Science Foundation (https://www.nsf.gov) (DEB-1442113 and DEB-1442148) and the DOE Great Lakes Bioenergy Research Center (https://www.glbrc.org) (DOE Office of Science DE-SC0018409). CTH is a Pew Scholar in the Biomedical Sciences, Vilas Faculty Early Career Investigator, and H. I. Romnes Faculty Fellow, supported by the Pew Charitable Trusts (https://www.pewtrusts.org), the Vilas Trust Estate (https://www.rsp.wisc.edu/Vilas), and the Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation (https://www.warf.org), respectively. AR is supported by a Guggenheim fellowship (https://www.gf.org/about/fellowship). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University (https://www.vanderbilt.edu/accre). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.