The effectiveness of selection in a species affects the direction of amino acid frequency evolution

Abstract

AbstractNearly neutral theory predicts that the effectiveness of natural selection will vary with species’ neutral genetic diversity, or effective population size (Ne). This relationship allows comparisons among species with different effective population sizes to reveal subtle selective preferences for a variety of traits. We investigate one such trait – amino acid composition – and find that the effectiveness of selection, measured as the Codon Adaptation Index of Species (CAIS), can predict amino acid frequencies across vertebrates. In addition to amino acid frequency (an evolutionary outcome), we also measure amino acid flux (an evolutionary process) on the branches separating mouse and rat, and compare it to flux on the branches separating human and chimpanzee. We decompose flux into a shared component that reflects a variety of universal artifacts, and a species-specific component capturing any effects ofNe. The shared component of flux is correlated with structural disorder propensity. The species component is correlated with selective preference as measured by CAIS, i.e., the two methods agree on which amino acids are preferred under more effective selection, with the CAIS method providing higher statistical resolution, and producing a correlation with random peptide fitness effects. Within highly exchangeable pairs of amino acids, arginine is strongly preferred over lysine, and valine over isoleucine. Interestingly, these preferences match how thermophiles tend to differ from mesophilic relatives, as expected from theories of marginal protein stability at mutation-selection-drift balance.