title: Systems genomics of metabolic phenotypes in wild-type Drosophila melanogaster.
abstract: Systems biology is an approach to dissection of complex traits that explicitly recognizes the impact of genetic, physiological, and environmental interactions in the generation of phenotypic variation. We describe comprehensive transcriptional and metabolic profiling in Drosophila melanogaster across four diets, finding little overlap in modular architecture. Genotype and genotype-by-diet interactions are a major component of transcriptional variation (24 and 5.3% of the total variation, respectively) while there were no main effects of diet (<1%). Genotype was also a major contributor to metabolomic variation (16%), but in contrast to the transcriptome, diet had a large effect (9%) and the interaction effect was minor (2%) for the metabolome. Yet specific principal components of these molecular phenotypes measured in larvae are strongly correlated with particular metabolic syndrome-like phenotypes such as pupal weight, larval sugar content and triglyceride content, development time, and cardiac arrhythmia in adults. The second principal component of the metabolomic profile is especially informative across these traits with glycine identified as a key loading variable. To further relate this physiological variability to genotypic polymorphism, we performed evolve-and-resequence experiments, finding rapid and replicated changes in gene frequency across hundreds of loci that are specific to each diet. Adaptation to diet is thus highly polygenic. However, loci differentially transcribed across diet or previously identified by RNAi knockdown or expression QTL analysis were not the loci responding to dietary selection. Therefore, loci that respond to the selective pressures of diet cannot be readily predicted a priori from functional analyses.
authors.affiliation: Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama 35497 lreed1@as.ua.edu.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Reed
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Development and Aging Program, Sanford-Burnham Medical Research Institute, San Diego, California 92037.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Lubna
authors.initials: L
authors.lastname: Rashid
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Amy
authors.initials: A
authors.lastname: Poe
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hsieh
authors.affiliation: Genomic Sciences Laboratory, North Carolina State University, Raleigh, North Carolina 27695 Huck Institutes of the Life Sciences, University Park, Pennsylvania 16802.
authors.forename: Nigel
authors.initials: N
authors.lastname: Deighton
authors.affiliation: Genomic Sciences Laboratory, North Carolina State University, Raleigh, North Carolina 27695 Bayer CropScience, Monheim, 40789, Germany.
authors.forename: Norm
authors.initials: N
authors.lastname: Glassbrook
authors.affiliation: Development and Aging Program, Sanford-Burnham Medical Research Institute, San Diego, California 92037.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Greg
authors.initials: G
authors.lastname: Gibson
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004032:Diet; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D049750:Genome, Insect; D023281:Genomics; D008297:Male; D055442:Metabolome; D010641:Phenotype; D012641:Selection, Genetic; D049490:Systems Biology; D059467:Transcriptome
keywords: adaptation; evolve-and-resequence; genotype-by-environment; metabolic syndrome; metabolomics