A Genomic Approach to Identify the Genetic Basis of Natural Variation in Lifespan and Age Specific Fecundity and their Plastic Responses to Diet in Drosophila melanogaster

Genetically based variation in lifespan and reproduction is pervasive in nature, and both traits are sensitive to changes in diet; however, we still know little about the actual genes influencing natural variation in lifespan and reproduction, and how these genes interact with environmental variables like diet to influence variation in lifespan and reproduction. I used the Drosophila melanogaster Genetic Reference Panel (DGRP), to complete a genome-wide association (GWA) study on lifespan, age specific fecundity, lifetime fecundity and the plastic response of these traits to changes in diet using mated Drosophila females reared as adults on either a high yeast (HY) diet or a low yeast (LY) diet. I identified a large number of candidate polymorphisms associated with each trait, and follow up studies using RNAi stocks validated the influence of a subset of candidates. I found very little overlap in candidate fecundity SNPs between ages, which suggests that the genetic basis of natural variation in fecundity changes dramatically with age. I also found that only 20 SNPs (0.97%) and 88 genes (8.55%) overlapped as candidates for age specific fecundity or lifespan on both diets, which suggests that individual genes influence lifespan and fecundity in a diet specific manner. I used the GWA results to test the predictions of two evolutionary theories of senescence(definition): mutation accumulation (MA) and antagonistic pleiotropy (AP) and the data provide strong evidence in support of MA at the nucleotide level. Finally, I tested the predictions of two hypotheses regarding the genetic mechanisms of phenotypic plasticity by comparing the results of the GWAs on trait means to the results of the GWAs on the plastic response to diet. I found evidence to support both theories, but most of the data supported the gene regulation hypothesis.