Gene x genotype interactions : epistasis for longevity, stress resistance, and mortality rates in Drosophila melanogaster
Spencer, Christine Courtney
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Senescence, the age related decline in fitness, is a maladaptive yet persistent phenomenon probably caused by the accumulation of deleterious mutations in late-acting genes. As with most polygenic traits, senescence or aging has the potential to be influenced by gene × gene or gene × genetic background interactions (epistasis). In collaboration with Daniel Promislow and others, I undertook three studies to examine the effect of genetic interactions on longevity and mortality rate parameters. In the first, I tested if overexpression of superoxide dismutase, which was found to extend longevity in a lab strain, would also increase lifespan in a series of wild-caught genetic backgrounds. I found ample evidence for gene × genetic background interactions. In particular, overexpression of the gene failed to increase lifespan in most male and some female genetic backgrounds. In the second study, I introgressed visible mutations into Drosophila and again showed that the effect of these visible mutations on longevity depended greatly on the genetic background in which they were expressed. The third study combined these same visible markers with one another to examine gene × gene interactions and their effects on longevity. When these markers were combined into a single genetic background, lifespan declined linearly as the number of mutations increased, but specific genetic combinations fell outside of this pattern of linear decline, indicating the presence of genetic interactions for longevity. Also, as the number of mutations increased, the baseline (age-independent) mortality rates changed dramatically, but the actual rate of aging (the rate of increase of age-specific mortality) showed little if any change. Overall, my results indicate that gene × gene and gene × genotype epistasis play an important role in the genetic determination of longevity. These results add to the small but expanding data on the importance of epistasis for fitness traits and suggest that such effects now need to be incorporated into models for the evolution of aging.