Analyses of allele age and fitness impact reveal human beneficial alleles to be older than neutral controls

Abstract

A classic population genetic prediction is that alleles experiencing directional selection should swiftly traverse allele frequency space, leaving detectable reductions in genetic variation in linked regions. However, despite this expectation, identifying clear footprints of beneficial allele passage has proven to be surprisingly challenging. We addressed the basic premise underlying this expectation by estimating the ages of large numbers of beneficial and deleterious alleles in a human population genomic data set. Deleterious alleles were found to be young, on average, given their allele frequency. However, beneficial alleles were older on average than non-coding, non-regulatory alleles of the same frequency. This finding is not consistent with directional selection and instead indicates some type of balancing selection. Among derived beneficial alleles, those fixed in the population show higher local recombination rates than those still segregating, consistent with a model in which new beneficial alleles experience an initial period of balancing selection due to linkage disequilibrium with deleterious recessive alleles. Alleles that ultimately fix following a period of balancing selection will leave a modest ‘soft’ sweep impact on the local variation, consistent with the overall paucity of species-wide ‘hard’ sweeps in human genomes.Analyses of allele age and evolutionary impact reveal that beneficial alleles in a human population are often older than neutral controls, suggesting a large role for balancing selection in adaptation.