Nearly 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 between species with differentNeto reveal selective preferences for a variety of traits, including those where the effects of selection may be subtle. We investigate one such trait — amino acid composition — and find that the efficacy 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 disorder propensity, while 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. Within highly exchangeable pairs of amino acids, we find strong preferences and flux imbalances in favor of arginine over lysine, and valine over isoleucine. Interestingly, these preferences are the same as those found in thermophilic lineages vs. mesophilic relatives.
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