Environmental perturbation increases gene expression variability and unmasks genetic regulation for transcriptional...

Environmental perturbation reshapes phenotypes not only by shifting trait means but also by modulating phenotypic variability. Whether environmentally induced changes in variability -environmental robustness- are genetically regulated remains unclear. To address this question, we collected nearly 2,000 matched genomes and transcriptomes from an outbred population of Drosophila melanogaster before and after exposure to a high-sugar diet, and quantified how dietary stress remodels expression variability and its genetic architecture. We find that environmental perturbation induces a transcriptome-wide increase in expression variability, with the notable exception of key developmental pathways. At the same time, stress unmasks pervasive genetic regulation for expression variability (veQTL). These loci are mostly environment-dependent, show distinct functional and evolutionary constraints from mean-regulating loci, and appeared detrimental when they confer to much robustness to dietary perturbation. Together, our findings establish gene expression variability as a central dimension of the organismal response to environmental changes, and uncover its genetic basis as a distinct, evolutionary constrained layer of phenotypic regulation beyond mean effects.