Recombination between genes with fitness interactions – how much is enough? Empirical data and simulations

Many of the effects on fitness population genetics is concerned with are due not to single locations in the genome, but due to the interaction of genetic variants at multiple locations in the genome. Of particular interest are ‘epistatic’ interactions, where a particular combination of genetic variants is required to produce an effect, and the effect cannot occur with any other combination. In diploids, models of these effects are difficult to analyse mathematically, as they are strongly influenced by meiotic recombination, a process which can both assemble and destroy combinations of genetic variants. Additionally, these interactions can be hard to detect in empirical studies, and so are regularly not considered. As a result, there is little consensus on when high levels of recombination might be expected, or how strongly recombination affects beneficial or deleterious fitness effects controlled by epistatic interactions. We address this question by conducting a meta-analysis, using data drawn and curated from Drosophila melanogaster studies in FlyBase. We developed a protocol for the extraction of studies relating genetic combinations and phenotypically detectable effects on fitness. Using the extracted data, we analysed the relationship between the rate of recombination and effect on fitness with a statistical model. We also ran simulations under a two-locus Wright-Fisher model with recombination and epistatic selection. The results of both approaches indicated a tendency for genetic combinations with some effect on fitness to have reduced meiotic recombination. Two possible explanations for this are that the variants controlling such interactions may only be retained in the population if they appear at locations with a low rate of recombination between them, or that such interactions lead to selection for lower rates of recombination.