Author:
Byrnes Juliet,Murray John,Tanaka Mark M.,Goldys Ben,Bellanto Antony,Cayetano Luis,Sherwin William
Abstract
AbstractMany of the effects on fitness in population genetics are due not to single locations in the genome, but to the interaction of genetic variants at multiple locations in the genome. Of particular interest are ‘completely epistatic’ interactions, where a combination of genetic variants is required to produce an effect, and the effect cannot occur with any other combination. In diploids, epistasis is strongly connected to meiotic recombination, a process which can both assemble and destroy beneficial combinations of genetic variants. Additionally, epistatic interactions can be hard to detect in empirical studies, and mathematical models of epistasis and recombination are challenging to analyse, so despite their ubiquity epistatic interactions 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 and simulations. The meta-analysis used data drawn and curated fromDrosophila melanogasterstudies in Flybase. We extracted studies relating genetic combinations and phenotypically detectable effects on fitness, then 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 an epistatic effect on fitness to occur in an environment of reduced meiotic recombination. Two possible explanations for this are that the variants controlling such interactions are selected for in regions where there is little recombination, or that such interactions lead to selection for lower rates of recombination in the regions where those variants appear.
Publisher
Cold Spring Harbor Laboratory
Reference196 articles.
1. Agrawal, N. , Joshi, S. , Kango, M. , Saha, D. , Mishra, A. , & Sinha, P . (1995). Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: Growth and pattern formation in genetic mosaics. Developmental Biology. http://doi.org/10.1006/dbio.1995.1155
2. A new look at the statistical model identification
3. Drosophila APC2 and APC1 Have Overlapping Roles in the Larval Brain Despite Their Distinct Intracellular Localizations
4. RNA interference from a CAX trinucleotide repeat
5. A Functional Screen Reveals an Extensive Layer of Transcriptional and Splicing Control Underlying RAS/MAPK Signaling in Drosophila;PLoS Biology,2014