Abstract
BackgroundLongevity and age-specific patterns of mortality are complex traits that vary within and among taxa. Multiple candidate genes for aging have been identified in model systems by extended longevity mutant phenotypes, including the G-protein coupled receptor methuselah (mth) in D. melanogaster. These genes offer important insights 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 variance for lifespan in natural populations, and consequently contribute to lifespan evolution.Methodology/Principle FindingsFor a gene to contribute to genetic variance for a particular trait, it must meet two criteria: natural allelic variation 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 demonstrate that mth alleles segregating in nature have a functional effect on all three traits.Conclusions/SignificanceThese results suggest that allelic variation 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.
Highlights
Lifespan and age specific mortality rates are primary life history components and vary significantly among natural populations [1]
Conclusions/Significance: These results suggest that allelic variation 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
In order to comprehensively examine the contribution of candidate genes for aging to the genetic variance for longevity and correlated traits, the functional significance of allelic variation must be assessed
Summary
Lifespan and age specific mortality rates are primary life history components and vary significantly among natural populations [1]. Such correlations may explain aspects of lifespan evolution, and why loss-of-function mutants can result in lifespan extension It remains unclear whether identified aging genes are major contributing factors to the genetic variance for longevity that is routinely observed in populations [e.g. 15]. Multiple candidate genes for aging have been identified in model systems by extended longevity mutant phenotypes, including the G-protein coupled receptor methuselah (mth) in D. melanogaster. These genes offer important insights into the mechanisms of lifespan determination and have been major targets of interest in the biology of aging. It is largely unknown whether these genes contribute to genetic variance for lifespan in natural populations, and contribute to lifespan evolution
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