A new codon adaptation metric predicts vertebrate body size and tendency to protein disorder

Abstract

AbstractThe nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic diversity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.