Report

Negative selection in humans and fruit flies involves synergistic epistasis

+ See all authors and affiliations

Science  05 May 2017:
Vol. 356, Issue 6337, pp. 539-542
DOI: 10.1126/science.aah5238

You are currently viewing the abstract.

View Full Text

Genetic interactions drive selection

Most individuals carry at least some potentially deleterious variants in their genome. But the effects of these mutations on individuals are not well understood. Sohail et al. examined loss-of-function (LOF) mutations in the genomes of humans and flies. They found that deleterious LOF mutations are further away from each other in the genome than expected by chance, which suggests that genetic interactions are driving selection. Thus, additional mutations do not exhibit an additive effect, and the overall selective parameter is not driven solely by the total number of mutations within the genome. This explains why high levels of variation can be maintained and why sex and recombination are advantageous.

Science, this issue p. 539

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.

View Full Text

Related Content