Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster

Abstract

BackgroundObesity and phenotypic traits associated with this condition exhibit significant heritability in natural populations of most organisms. While a number of genes and genetic pathways have been implicated to play a role in obesity associated traits, the genetic architecture that underlies the natural variation in these traits is largely unknown. Here, we used 40 wild-derived inbred lines of Drosophila melanogaster to quantify genetic variation in body weight, the content of three major metabolites (glycogen, triacylglycerol, and glycerol) associated with obesity, and metabolic rate in young flies. We chose these lines because they were previously screened for variation in whole-genome transcript abundance and in several adult life-history traits, including longevity, resistance to starvation stress, chill-coma recovery, mating behavior, and competitive fitness. This enabled us not only to identify candidate genes and transcriptional networks that might explain variation for energy metabolism traits, but also to investigate the genetic interrelationships among energy metabolism, behavioral, and life-history traits that have evolved in natural populations.ResultsWe found significant genetically based variation in all traits. Using a genome-wide association screen for single feature polymorphisms and quantitative trait transcripts, we identified 337, 211, 237, 553, and 152 novel candidate genes associated with body weight, glycogen content, triacylglycerol storage, glycerol levels, and metabolic rate, respectively. Weighted gene co-expression analyses grouped transcripts associated with each trait in significant modules of co-expressed genes and we interpreted these modules in terms of their gene enrichment based on Gene Ontology analysis. Comparison of gene co-expression modules for traits in this study with previously determined modules for life-history traits identified significant modular pleiotropy between glycogen content, body weight, competitive fitness, and starvation resistance.ConclusionsCombining a large phenotypic dataset with information on variation in genome wide transcriptional profiles has provided insight into the complex genetic architecture underlying natural variation in traits that have been associated with obesity. Our findings suggest that understanding the maintenance of genetic variation in metabolic traits in natural populations may require that we understand more fully the degree to which these traits are genetically correlated with other traits, especially those directly affecting fitness.

Host Genetic Control of the Microbiota Mediates the Drosophila Nutritional Phenotype

“…It extends previous research demonstrating strong statistical associations between genotype and multiple nutritional indices in the DGRP (45) to reveal that members of the microbiota are correlated with certain host nutritional indices. Multiple lines of evidence indicate that the bacteria are the causal basis of these correlations, at least with respect to the Acetobacteraceae: flies bearing Acetobacteraceae, but not Lactoba- Table S1 in the supplemental material.…”

Metabolism, Growth, and the Energetic Definition of Fitness: A Quantitative Genetic Study in the Land SnailCornu aspersum

“…Today, few estimations of genetic (co)variances for bioenergetic traits in invertebrates are available, which contrasts with the complete picture of the heritable variation and fitness covariation of energy metabolism in vertebrates (see Nespolo et al 2005;Ronning et al 2007;Wone et al 2009 and references therein). In fact, we have been unable to find quantitative genetic studies of invertebrate energy metabolism other than in insects (Rantala and Roff 2006;Nespolo et al 2007Nespolo et al , 2011Ketola and Kotiaho 2009;Arnqvist et al 2010;Jumbo-Lucioni et al 2010;Artacho et al 2011;Piiroinen et al 2011), which indeed show low levels of additive genetic variation. This omission needs attention since noninsect invertebrates represent a vast proportion of multicellular animals inhabiting a broad array of habitats and, hence, exhibiting varied physiological adaptations.…”

Gut microbiota dictates the metabolic response ofDrosophilato diet

“…To our knowledge, the microbiota has not been considered previously in the many demonstrations of between-sex differences in Drosophila metabolism and metabolism gene expression patterns (Ayroles et al, 2009;Bauer et al, 2006;Bharathi et al, 2003;Greenberg et al, 2011;Jumbo-Lucioni et al, 2010;Lushchak et al, 2014;Scheitz et al, 2013), although there is evidence for sex-specific impacts of the microbiota on metabolic traits of the mouse (Markle et al, 2013). The processes contributing to interactions between the microbiota and host metabolism are likely multiple and interactive.…”