Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection.

ABSTRACT: Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here, we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions

SUBMITTER: Lenz TL 

PROVIDER: S-EPMC5026253 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature