A single nucleotide variant in the PPARγ-homologEip75Baffects fecundity inDrosophila

Single nucleotide polymorphisms are the most common type of genetic variation, but how these variants contribute to the evolutionary adaptation of complex phenotypes is largely unknown. Experimental evolution and genome-wide association studies have demonstrated that variation in the PPARg-homologEip75Bis associated with longevity and life-history differences in the fruit flyDrosophila melanogaster. Using RNAi knockdown, we first demonstrate that reduced expression ofEip75Bin adults affects lifespan, egg-laying rate and egg volume. We then tested the effect of a naturally occurring SNP variant within a cis-regulatory domain ofEip75Bby applying two complementary approaches: a Mendelian randomization approach using lines of theDrosophilaGenetic Reference Panel, and allelic replacement using precise CRISPR/Cas9-induced genome editing. Our experiments reveal that this natural polymorphism has a significant pleiotropic effect on fecundity and egg-to-adult viability, but not on longevity or other life-history traits. These results provide a rare functional validation at the nucleotide level and identify a natural allelic variant affecting fitness and life-history adaptation.