Natural variation in phospholipase IPLA2-VIA contributes to starvation sensitivity in Drosophila melanogaster

Abstract Resistance to starvation is a classic complex trait where genetic and environmental variables can greatly modify an animal’s ability to survive without nutrients. Genetic analyses in Drosophila have shown that starvation resistance is highly polygenic with different genetic architectures in different mapping populations. In this study we sought to dissect the genetic basis of starvation resistance among a set of mitonuclear genotypes carrying different mtDNAs paired with specific nuclear genomes from the Drosophila Genetic Reference Panel (DGRP). We focused on differences between one of the most sensitive strains (DGRP-765) and a strain with more moderate resistance (DGRP-315) whose starvation phenotypes appeared to be modified by alternative mtDNAs. Using complementary pooled-sequencing and forward genetic mapping approaches, we identified regions of chromosomes 2L, 3L and 3R contributing to starvation sensitivity and localize a major effect locus modifying starvation resistance to the coding region of phospholipase iPLA2-VIA. These analyses further confirm that the alternative mtDNAs had little influence on variation in starvation resistance between the genotypes studied. The sensitive line shows a starvation-dependent depletion of glucose and glycogen that is modified by hemi- and heterozygosity in the iPLA2-VIA region. These findings contribute to our understanding of the complex genetic relationship between resistance to starvation stress and nutrient metabolism. Competing Interest Statement The authors have declared no competing interest. Footnotes This manuscript has been revised and submitted for publication in G3. The revision includes revised text of the manuscript, additional figures, more detailed explanations of genetic analyses and additional references. The associated GitHub site has additional details of revisions to figures. https://github.com/DavidRandLab/Williams-et-al.-Starvation-Genetics-2021 The figures have been revised and have different Figure numbers in this repo than in the G3 manuscript under review. Until this repo is revised, the following figure changes have been made: Figure 1 in this repo is Figure 3 in the G3 manuscript Figure 2 in this repo has divided into Figure 2 and Figure 4 in the G3 manuscript Figure 3 in this repo is Figure 5 in the G3 manuscript Figure 4 in this repo is Supplementary Fig. S4 in the G3 manuscript Figure 5 in this repo is Figure 6 in the G3 Manuscript Supplemental Figure S1 in this repo is Supplemental Fig. 2 in the G3 manuscript Supplemental Figure S2 in this repo is Supplemental Fig. 3 in the G3 manuscript Supplemental Figure S3 in this repo is Figure 7 in the G3 manuscript. The R codes for the older figure versions are intact and updated R codes for the relevant changes will be added once the manuscript is published. https://github.com/DavidRandLab/Williams-et-al.-Starvation-Genetics-2021