Negative selection in humans and fruit flies involves synergistic epistasis

Genome of the Netherlands Consortium, Alzheimer's Disease Neuroimaging Initiative

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection. However, it is not known whether deleterious alleles affect fitness independently, so that cumulative fitness loss depends exponentially on the number of deleterious alleles, or synergistically, so that each additional deleterious allele results in a larger decrease in relative fitness. Negative selection with synergistic epistasis should produce negative linkage disequilibrium between deleterious alleles and, therefore, an underdispersed distribution of the number of deleterious alleles in the genome. Indeed, we detected underdispersion of the number of rare loss-of-function alleles in eight independent data sets from human and fly populations. Thus, selection against rare protein-disrupting alleles is characterized by synergistic epistasis, which may explain how human and fly populations persist despite high genomic mutation rates.

    Original languageEnglish
    Pages (from-to)539-542
    Number of pages4
    JournalScience
    Volume356
    Issue number6337
    DOIs
    Publication statusPublished - 5 May 2017

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