Estimating the proportion of beneficial mutations that are not adaptive in mammals

Abstract

Mutations can be beneficial by bringing innovation to their bearer, allowing them to adapt to environmental change. These mutations are typically unpredictable since they respond to an unforeseen change in the environment. However, mutations can also be beneficial because they are simply restoring a state of higher fitness that was lost due to genetic drift in a stable environment. In contrast to adaptive mutations, these beneficial non-adaptive mutations can be predicted if the underlying fitness landscape is stable and known. The contribution of such non-adaptive mutations to molecular evolution has been widely neglected mainly because their detection is very challenging. We have here reconstructed protein-coding-gene fitness landscapes shared between mammals, using mutation-selection models and a multi-species alignments across 87 mammals. These fitness landscapes have allowed us to predict the fitness effect of polymorphisms found in 28 mammalian populations. Using methods that quantify selection at the population level, we have confirmed that beneficial non-adaptive mutations are indeed positively selected in extant populations. Our work confirms that deleterious substitutions are accumulating in mammals and are being reverted, generating a balance in which genomes are damaged and restored simultaneously at different loci. We observe that beneficial non-adaptive mutations represent between 15% and 45% of all beneficial mutations in 24 of 28 populations analyzed, suggesting that a substantial part of ongoing positive selection is not driven solely by adaptation to environmental change in mammals. Significance statementThe extent to which adaptation to changing environments is shaping genomes is a central question in molecular evolution. To quantify the rate of adaptation, population geneticists have typically used signatures of positive selection. However, mutations restoring an ancestral state of higher fitness lost by genetic drift are also positively selected, but they do not respond to a change in the environment. In this study, we have managed to distinguish beneficial mutations that are due to changing environments and those that are restoring pre-existing functions in mammals. We show that a substantial proportion of beneficial mutations cannot be interpreted as adaptive.