A Single Nucleotide Variant in the PPARγ-homolog Eip75B Affects Fecundity in Drosophila. (27th January 2023)

• Record Type: Journal Article
• Authors: Hoedjes, Katja M; Kostic, Hristina; Flatt, Thomas; Keller, Laurent
• Editors: Wittkopp, Patricia
• Is Part Of: Molecular biology and evolution. Volume 40:Number 2(2023)
• Publication Date: 2023-01-27
• Subjects: pleiotropy -- Drosophila -- aging -- reproduction -- CRISPR/Cas9 -- RNAi; Molecular biology -- Periodicals; Molecular evolution -- Periodicals; Evolution, Molecular -- Periodicals; Molecular Biology -- Periodicals; 572.8
• DOI: 10.1093/molbev/msad018
• Languages: English
• ISSNs: 0737-4038

Abstract

Abstract: Single nucleotide polymorphisms are the most common type of genetic variation, but how these variants contribute to the adaptation of complex phenotypes is largely unknown. Experimental evolution and genome-wide association studies have demonstrated that variation in the PPARγ-homolog Eip75B has associated with longevity and life-history differences in the fruit fly Drosophila melanogaster . Using RNAi knockdown, we first demonstrate that reduced expression of Eip75B in adult flies affects lifespan, egg-laying rate, and egg volume. We then tested the effects of a naturally occurring SNP within a cis-regulatory domain of Eip75B by applying two complementary approaches: a Mendelian randomization approach using lines of the Drosophila Genetic 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. Our results provide a rare functional validation at the nucleotide level and identify a natural allelic variant affecting fitness and life-history adaptation.