Data from: Dietary stress unmasks cryptic genetic variation regulating lifespan in outbred Drosophila

Evolutionary theory suggests that lifespan-associated alleles should be
purged from the gene pool, and yet decades of GWAS and model organism
studies have shown they persist. Here, we address one potential
explanation, the idea that the alleles that regulate lifespan do so only
in certain contexts. We exposed thousands of outbred Drosophila
to a standard and a high sugar diet. We then sequenced over 10,000
individuals and track genome-wide allele frequency changes over time, as
these populations aged. We mapped thousands of lifespan-altering alleles,
some associated with early- vs late-life tradeoffs, late-onset effects,
and genotype-by-environment interactions. We find that lifespan-reducing
alleles are most likely to be recently derived and have stronger effects
on a high-sugar diet, consistent with the hypothesis that historically
neutral or beneficial alleles can become detrimental in novel conditions.
We also show that the gene midway, a regulator of lipid storage and
ortholog of the lifespan-associated gene DGAT1 in mice, also regulates
lifespan in Drosophila. Our results provide insight into the
highly polygenic and context-dependent genetic architecture of lifespan,
as well as the evolutionary processes that shape this key trait.