Conventionally the phenotypic outcome of a mutation is considered to be due to a specific DNA lesion. But it has long been known that mutational effects can be conditional on environment (GxE) and genetic background (GxG). Thus it is standard practice to perform experiments by controlling for rearing environment and using co-isogenic strains. Though such a controlled approach has been very successful in enabling many discoveries, by not considering conditional effects our understanding of biological systems is incomplete. My research utilized conditionality in terms of genetic background and standing genetic variation therein to understand whether mutational interactions can themselves be background dependent. I demonstrated that a majority of mutational interactions identified via a dominant modifier screen are background dependent. Extending this idea of contingency in terms of standing genetic variation to the phenomenon of compensatory evolution in the presence of deleterious mutations, I demonstrated that natural populations of Drosophila melanogaster possess standing genetic variation for compensatory alleles to ameliorate even severe phenotypic defects. I further demonstrated that, despite considerable standing variation to ameliorate the focal phenotype perturbed by the mutation, natural selection exploits alternative evolutionary trajectories to recover fitness. Additionally this model system also allowed me to understand that loss of sexual signaling can be compensated by modulating behavioural and life history traits.
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