Natural alleles at the Doa locus underpin evolutionary changes in Drosophila lifespan and fecundity

Abstract

‘Evolve and resequence’ (E&R) studies in Drosophila melanogaster have identified many candidate loci underlying the evolution of ageing and life history, but experiments that validate the effects of such candidates remain rare. In a recent E&R study we have identified several alleles of the LAMMER kinase Darkener of apricot ( Doa ) as candidates for evolutionary changes in lifespan and fecundity. Here, we use two complementary approaches to confirm a functional role of Doa in life-history evolution. First, we used transgenic RNAi to study the effects of Doa at the whole-gene level. Ubiquitous silencing of expression in adult flies reduced both lifespan and fecundity, indicating pleiotropic effects. Second, to characterize segregating variation at Doa , we examined four candidate single nucleotide polymorphisms (SNPs; Doa-1 , - 2 , - 3 , -4 ) using a genetic association approach. Three candidate SNPs had effects that were qualitatively consistent with expectations based on our E&R study: Doa-2 pleiotropically affected both lifespan and late-life fecundity; Doa-1 affected lifespan (but not fecundity); and Doa-4 affected late-life fecundity (but not lifespan). Finally, the last candidate allele ( Doa-3 ) also affected lifespan, but in the opposite direction from predicted.

A Single Nucleotide Variant in the PPARγ-homolog Eip75B Affects Fecundity in Drosophila

“…Instead, functional analyses are often performed at the gene level by generating (null) mutants or using RNAi ( Zhou et al 2011 ; Martins et al 2014 ; Fabian et al 2018 ; Huang et al 2020 ; Parker et al 2020 ). Functional effects of natural alleles may, however, be more subtle than or different altogether from those of mutant alleles ( Stern 2011 ; Mokashi et al 2021 ; Hoedjes et al 2022 ). The aim of this study was to perform functional analyses of a natural polymorphism of Ecdysone-induced protein 75B ( Eip75B ), a candidate gene for aging and life-history evolution in fruit flies.…”

A single nucleotide variant in the PPARγ-homologEip75Baffects fecundity inDrosophila

“…Functional effects of natural alleles may, however, be more subtle or different altogether from mutant alleles (Stern 2011;Mokashi, et al 2021;Hoedjes, et al 2022). The aim of this study was to conduct functional analyses of a natural polymorphism of Ecdysone-induced protein 75B (Eip75B), a candidate gene for ageing and life-history evolution in fruit flies.…”

“…Instead, functional analyses are often performed at the gene level by generating (null) mutants or using RNAi (Zhou, et al 2011; Martins, et al 2014; Fabian, et al 2018; Huang, et al 2020; Parker, et al 2020). Functional effects of natural alleles may, however, be more subtle or different altogether from mutant alleles (Stern 2011; Mokashi, et al 2021; Hoedjes, et al 2022). The aim of this study was to conduct functional analyses of a natural polymorphism of Ecdysone-induced protein 75B (Eip75B ), a candidate gene for ageing and life-history evolution in fruit flies.…”