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Nat Commun. 2014 Jul 8;5:4338. doi: 10.1038/ncomms5338.

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

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Department of Biological Sciences, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA.


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.

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