David Castellano: Comparison of the full distribution of fitness effects of new amino acid mutations across great apes

Since the distribution of fitness effects (DFE) of new deleterious amino acid mutations was first inferred from polymorphism data in humans, more than a decade ago, there has been considerable interest in describing the form of the DFE in many other species. It has been shown, that the DFE of new deleterious mutations is more leptokurtic in humans than Drosophila – this has been attributed to a higher phenotypic complexity in humans than Drosophila. Nevertheless, there are still very few comparative studies of the DFE between species, especially between closely related species. We provide the first comparison of the full DFE (which includes deleterious, neutral but also beneficial mutations) in the great apes. We investigate which aspects of the full DFE are likely shared and which aspects are variable. Our analysis suggests that the shape of the deleterious DFE is remarkably constant across great apes, but the mean effect size of deleterious mutations has not remained constant as commonly assumed. We find that, on average, new deleterious mutations are more deleterious in large populations, consistent with positive epistasis. We also find that for the two smallest great ape populations, western chimpanzees and bonobos, the mean effect size of deleterious mutations is larger than expected given their effective population size.

Reference: Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes. David Castellano, Moisès Coll Macià, Paula Tataru, Thomas Bataillon and Kasper Munch. GENETICS Early online September 5, 2019; https://doi.org/10.1534/genetics.119.302494.