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

The white (w) gene, one of the most widely used genetic markers in Drosophila research, serves as a standard background mutation for transgene insertions and genetic manipulations1. While its primary function involves eye pigmentation, mutations in white have been associated with diverse phenotypic effects, including those related to metabolism, behavior, and stress responses2-19. However, many studies using these mutants do not account for differences in genetic background, raising concerns about the interpretation of experimental results. 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 deletion 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 loss of white influences multiple biological processes beyond its established role in eye pigmentation. These results emphasize the necessity of genetic background control in Drosophila research and warrant caution when using white mutants as a baseline for comparative studies.