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Mutation of the white gene in Drosophila has widespread phenotypic and transcriptomic effects

ABSTRACT: The white (w) gene is one of the most widely used genetic markers in Drosophila research, serving as a standard background mutation for transgene insertions and genetic manipulations. While its primary function is in eye pigmentation, w mutations have been associated with diverse phenotypic effects including in metabolism, behavior, and stress responses. However, many studies using w mutants do not account for differences in genetic background, raising concerns about the interpretation of experimental results. Given the potential confounding genetic effects and non-pigment related roles of w, we generated a well-controlled phenotyping dataset. To ensure that the observed phenotypic differences are attributable to white itself, rather than other genetic differences due to background, we established isogenic fly strains through backcrossing that differ only by the presence or absence of the white gene. Given the likely metabolic consequences of white gene dysfunction and its crucial role in neurotransmitter production, we focused our phenotyping assays on behavioral, metabolic and fitness related outcomes and performed transcriptomic analysis on adult fly heads. Our findings reveal widespread changes in adult brain gene expression and behavioral, metabolic and fitness traits, demonstrating that w mutations influence multiple biological processes beyond their established role in pigment transport. These results emphasize the necessity of genetic background control in Drosophila research and suggest that caution is warranted when using w mutants as a baseline for comparative studies.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE290227 | GEO | 2025/03/03

REPOSITORIES: GEO

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Project description:Ramirez2017 - Human global metabolism in brown and white adipocytes Recon 2.1A, an update to Recon 2.1x, is suitable for quantitatively-realistic results for flux balance analysis in human metabolism. This model is described in the article: Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes. Ramirez AK, Lynes MD, Shamsi F, Xue R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM. Cell Rep 2017 Dec; 21(11): 3040-3048 Abstract: White adipocytes are specialized for energy storage, whereas brown adipocytes are specialized for energy expenditure. Explicating this difference can help identify therapeutic targets for obesity. A common tool to assess metabolic differences between such cells is the Seahorse Extracellular Flux (XF) Analyzer, which measures oxygen consumption and media acidification in the presence of different substrates and perturbagens. Here, we integrate the Analyzer's metabolic profile from human white and brown adipocytes with a genome-scale metabolic model to predict flux differences across the metabolic map. Predictions matched experimental data for the metabolite 4-aminobutyrate, the protein ABAT, and the fluxes for glucose, glutamine, and palmitate. We also uncovered a difference in how adipocytes dispose of nitrogenous waste, with brown adipocytes secreting less ammonia and more urea than white adipocytes. Thus, the method and software we developed allow for broader metabolic phenotyping and provide a distinct approach to uncovering metabolic differences. This model is hosted on BioModels Database and identified by: MODEL1703310000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Mutation of the white gene in Drosophila has widespread phenotypic and transcriptomic effects

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