In this project, we have studied a unique set of 24 experimentally evolved (EE) populations of fruit flies that adapted their lifespan in response to selection on postponed reproduction and/or adaptation to a poor larval diet. We have analysed the genomes of these populations to identify loci that diverged in response to one or both selective regimes. Overall, our analyses did not indicate an overrepresentation of candidate genes involved in lipid metabolism or nutrient sensing, or other known "aging" genes. This suggests that naturally occurring variants involved in longevity evolution are distinct from variants identified through classical mutant screens. However, there was a significant overlap of our candidates with those identified in other independent longevity EE studies, which may indicate the presence of preferred targets of selection for the evolution of lifespan. In parallel, we have characterized fat metabolism of the EE lines, by measuring fat content and starvation resistance. These experiments indicated a strong effect of age on both fat content and starvation resistance, but only modest differentiation in response to the two selective regimes. This finding supports the results of our genomic analyses, and again suggests a limited role for nutrient sensing or metabolic pathways in the evolution of lifespan in these EE lines. We then performed in-depth functional genetic tests on two of our candidate genes, and SNPs therein: the LAMMER protein kinase Doa and the nuclear hormone receptor Eip75B. By doing RNAi and association experiments, we confirmed that both genes play a role in lifespan, as well as reproduction, and we identified the most likely candidate SNP responsible for this effect. These findings provide novel insights into how aging evolves in concert with other life history phenotypes.
As part of this project, a review on the effects of dietary amino acids on lifespan and reproduction was published in Current Opinion in Insect Science. The results have been presented at five international conferences and at ten seminars.
