title: Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits.
abstract: Most organisms exhibit senescence; a decline in physiological function with age. In nature, rates of senescence vary extensively among individuals and this variation has a significant genetic component; however, we know little about the genes underlying senescence. Here we show the first evidence that individual alleles influence fecundity in an age-specific manner and so the genetic basis of natural variation in fecundity changes dramatically with age. We complete a genome-wide association to identify single-nucleotide polymorphisms (SNPs) affecting lifespan and age-specific fecundity using the Drosophila melanogaster Genetic Reference Panel. We identify 1,031 SNPs affecting fecundity and 52 influencing lifespan. Only one SNP is associated with both early- and late-age fecundity. The age-specific effect of candidate genes on fecundity is validated using RNA interference. In addition, there is a dramatic increase in the number of SNPs influencing fecundity with age. This result provides support for the mutation accumulation theory of aging.
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Durham
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Magwire
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Leips
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005298:Fertility / Q000235:genetics*; D063990:Gene Ontology; D056084:Genetic Fitness / Q000235:genetics*; D055106:Genome-Wide Association Study; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide