Effect of Correlated TRAN Abundances on Translation Errors and Evolution of Codon Usage Bias

Abstract Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB) assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on tRNA competition and intra-ribosomal kinetics, we show that this assumption can be violated when tRNA abundances are positively correlated across the genetic code. Examining the distribution of tRNA abundances across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. This work challenges one of the fundamental assumptions made in over 30 years of research on CUB that codons with higher tRNA abundances have lower missense error rates and that missense errors are the primary selective force responsible for CUB. Author Summary Codon usage bias (CUB) is a ubiquitous and important phenomenon. CUB is thought to be driven primarily due to selection against missense errors. For over 30 years, the standard model of translation errors has implicitly assumed that the relationship between translation errors and tRNA abundances are inversely related. This is based on an implicit and unstated assumption that the distribution of tRNA abundances across the genetic code are uncorrelated. Examining these abundance distributions across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. We further show that codons with higher tRNA abundances are not always “optimal” with respect to reducing the missense error rate and hence cannot explain the observed patterns of CUB. DOI: 10.1371/journal.pgen.100112