Epistasis for quantitative traits in Drosophila.

Abstract

The role of gene-gene interactions in the genetic architecture of quantitative traits is controversial, despite the biological plausibility of nonlinear molecular interactions underpinning variation in quantitative traits. In strictly outbreeding populations, genetic architecture is inferred indirectly by estimating variance components; however, failure to detect epistatic variance does not mean lack of epistatic gene action and is even consistent with pervasive epistasis. In Drosophila, more focused approaches to detecting epistatic gene action are possible, based on the ability to create de novo mutations and perform crosses among them; to construct inbred lines, artificial selection lines, and chromosome substitution lines; to map quantitative trait loci affecting complex traits by linkage and association; and to evaluate effects of induced mutations on multiple wild-derived backgrounds. Here, I review evidence for epistasis in Drosophila from the application of these methods, and conclude that additivity is an emergent property of underlying epistatic gene action for Drosophila quantitative traits. Such studies can be used to infer novel, highly interconnected genetic networks that are enriched for gene ontology categories and metabolic and cellular pathways. The consequence of epistasis is that the main effects of each of the interacting loci depend on allele frequency, which negatively impacts the predictive ability of additive models. Finally, epistasis results in hidden quantitative genetic variation in natural populations (genetic canalization) and the potential for rapid evolution of Dobzhansky-Muller incompatibilities (speciation).