Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits

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.