Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Graduate Group


First Advisor

Paul S. Schmidt


Life history traits are critical components of fitness and frequently reflect adaptive responses to environmental pressures. Natural populations of Drosophila melanogaster exhibit patterns of lifespan, fecundity, development time, body size and stress resistance that vary predictably along environmental gradients. Artificial selection studies, genetic correlation analyses, and quantitative trait mapping efforts have demonstrated a genetic basis for the observed phenotypic variation, but few genes have been identified that contribute to natural life history variation. This work employs a candidate gene approach to discover genes and specific polymorphisms that contribute to genetic variance for D. melanogaster life history. Three aging genes, which have been characterized to mediate longevity, reproduction and stress tolerance, have been evaluated for natural genetic variation from samples derived from the wild. Allelic variation at one gene, methuselah (mth), shows functional effects on lifespan, lifetime fecundity and resistance to oxidative stress. A polymorphism in the mth promoter has been identified which may contribute to variation in these traits by affecting levels of gene expression. Natural genetic variation at two genes in the insulin signaling pathway reveals a history of positive selection at the Insulin-like Receptor (InR), but evidence of neutral evolution at the InR substrate, chico. Furthermore, an indel polymorphism in the first exon of InR shows striking, nonrandom distributions on two continents, a sign that it may contribute to the observed patterns of phenotypic variation across these same habitats. Functional evaluation of alternate InR alleles demonstrates predictable effects on phenotype and levels of insulin signaling, which implicates this polymorphism in the adaptive evolution of wild D. melanogaster populations. These findings provide novel examples of how allelic variation underlies adaptive changes in life history evolution, and contribute complementary characterization of genetic function to the biology of aging.

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