Stronger and higher proportion of beneficial amino acid changing mutations in humans compared to mice and flies

Abstract

Quantifying and comparing the amount of adaptive evolution among different species is key to understanding evolutionary processes. Previous studies have shown differences in adaptive evolution across species, however their specific causes remain elusive. Here, we use improved modeling of weakly deleterious mutations and the demographic history of the outgroup species and estimate that 30-34% of nonsynonymous substitutions between humans and outgroup species have been fixed by positive selection. This estimate is much higher than previous estimates, which did not account for the population size of the outgroup species. Next, we directly estimate the proportion and selection coefficients of newly arising strongly beneficial nonsynonymous mutations in humans, mice, and D. melanogaster by examining patterns of polymorphism and divergence. We develop a novel composite likelihood framework to test whether these parameters differ across species. Overall, we reject a model with the same proportion and the same selection coefficients of beneficial mutations across species, and estimate that humans have a higher proportion of beneficial mutations compared to Drosophila and mice. We demonstrate that this result cannot be attributed to biased gene conversion. In summary, we find the proportion of beneficial mutations is higher in humans than in D. melanogaster or mice, suggesting that organismal complexity, which increases the number of steps required in adaptive walks, may be a key predictor of the amount of adaptive evolution within a species.