Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila

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dc.contributor.authorWilliams, Stephanie
dc.contributor.authorDew-Budd, Kelly
dc.contributor.authorDavis, Kristen
dc.contributor.authorAnderson, Julie
dc.contributor.authorBishop, Ruth
dc.contributor.authorFreeman, Kenda
dc.contributor.authorDavis, Dana
dc.contributor.authorBray, Katherine
dc.contributor.authorPerkins, Lauren
dc.contributor.authorHubickey, Joana
dc.contributor.authorReed, Laura K.
dc.contributor.otherNorth Carolina State University
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.date.accessioned2023-09-28T22:05:20Z
dc.date.available2023-09-28T22:05:20Z
dc.date.issued2015
dc.description.abstractGenetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationWilliams, S., Dew-Budd, K., Davis, K., Anderson, J., Bishop, R., Freeman, K., Davis, D., Bray, K., Perkins, L., Hubickey, J., & Reed, L. K. (2015). Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila. In G3 Genes|Genomes|Genetics (Vol. 5, Issue 12, pp. 2817–2829). Oxford University Press (OUP). https://doi.org/10.1534/g3.115.023564
dc.identifier.doi10.1534/g3.115.023564
dc.identifier.orcidhttps://orcid.org/0000-0003-3791-2241
dc.identifier.orcidhttps://orcid.org/0000-0001-7440-5156
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12328
dc.languageEnglish
dc.language.isoen_US
dc.publisherGenetics Society of America
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectmetabolomics
dc.subjectgenotype-by-environment interaction
dc.subjectmetabolic syndrome
dc.subjectDrosophila
dc.subjectcanalization
dc.subjectINSULIN-RESISTANCE
dc.subjectJUVENILE-HORMONE
dc.subjectADIPOSE-TISSUE
dc.subjectPALMITIC ACID
dc.subjectLEUCINE
dc.subjectTRANSITIONS
dc.subjectASSOCIATION
dc.subjectVALIDATION
dc.subjectISOLEUCINE
dc.subjectGENOTYPE
dc.subjectGenetics & Heredity
dc.titleMetabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophilaen_US
dc.typeArticle
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