The action of stabilizing selection, mutation, and drift on epistatic quantitative traits

For a quantitative trait under stabilizing selection, the effect of epistasis on its genetic architecture and on the changes of genetic variance caused by bottlenecking were investigated using theory and simulation. Assuming empirical estimates of the rate and effects of mutations and the intensity of selection, we assessed the impact of two-locus epistasis (synergistic/antagonistic) among linked or unlinked loci on the distribution of effects and frequencies of segregating loci in populations at the mutation-selection-drift balance. Strong pervasive epistasis did not modify substantially the genetic properties of the trait and, therefore, the most likely explanation for the low amount of variation usually accounted by the loci detected in genome-wide association analyses is that many causal loci will pass undetected. We investigated the impact of epistasis on the changes in genetic variance components when large populations were subjected to successive bottlenecks of different sizes, considering the action of genetic drift, operating singly (D), or jointly with mutation (MD) and selection (MSD). An initial increase of the different components of the genetic variance, as well as a dramatic acceleration of the between-line divergence, were always associated with synergistic epistasis but were strongly constrained by selection.