Negative selection in humans and fruit flies involves synergistic epistasis

Mashaal Sohail, Olga A Vakhrusheva, Jae Hoon Sul, Sara L Pulit, Laurent C Francioli, Leonard H van den Berg, Jan H Veldink, Paul I W de Bakker, Georgii A Bazykin, Alexey S Kondrashov, Shamil R Sunyaev, Genome of the Netherlands Consortium, A. Abdellaoui, J.J. Hottenga, Gonneke Willemsen, D.I. Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review

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

    Fingerprint

Keywords

  • Journal Article

Cite this

Sohail, M., Vakhrusheva, O. A., Sul, J. H., Pulit, S. L., Francioli, L. C., van den Berg, L. H., ... Boomsma, D. I. (2017). Negative selection in humans and fruit flies involves synergistic epistasis. Science, 356(6337), 539-542. https://doi.org/10.1126/science.aah5238