title: 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 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.
  
  
  RESULTS
  For 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
  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.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States of America. paaby@sas.upenn.edu
authors.forename: Annalise B
authors.initials: AB
authors.lastname: Paaby
authors.forename: Paul S
authors.initials: PS
authors.lastname: Schmidt
mesh_terms: D000375:Aging; D000483:Alleles; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005816:Genetic Complementation Test; D014644:Genetic Variation; D008136:Longevity; D008957:Models, Genetic; D018384:Oxidative Stress; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila