Functional significance of allelic variation at methuselah, an aging gene in Drosophila

Abstract

Background: Longevity and age-specific patterns of mortality are complex traits that vary withim and among taxa. Multiple candidate genes for aging have been identified in model systems by extended longevity mutant phenotype, including the G-protein coupled receptor methuselah (mth) in D. melanogaster. These genes offer important insight into the mechanisms of lifespan determination and have been major targets of interest in the biology of aging. However, it is largely unknown whether these genes contribute to genetic for lifespan in natural populations, and consequently contribute to lifespan evolution. Methodology/Principle Findings: For a gene to contribute to genetic variance for a particular trait, it must meet two criteria: natural allelic variations and functional differences among variants. Previous work showed that mth varies significantly among wild populations; here we assess the functional significance of wild-derived mth alleles on lifespan, fecundity and stress resistance using a quantitative complementation scheme. Our results demonstrated that mth alleles segregating in nature have a functional effect on all three traits. Conclusions/Significance: These results suggest that allelec variations at mth contributes to observed differences in lifespan and correlated phenotypes in natural populations, and that evaluation of genetic diversity at candidate genes for aging can be a fruitful approach to identifying loci contributing to lifespan evolution. © 2008 Paaby, Schmidt.