Dietary landscapes shape genotype- and sex-specific responses to insecticides

Insecticide resistance is typically studied as a response to chemical toxicity, yet in natural and agricultural systems insecticides are embedded within food resources. How resistance alleles interact with nutritional environments to shape fitness remains largely unknown. Here we combine nutritional geometry approaches to test how variation at a major resistance locus, Cyp6g1, modifies sex-specific reproductive performance across dietary landscapes in Drosophila melanogaster. We show that a resistance allele does more than increase survival: it profoundly reshapes reproductive allocation in both sexes. Resistant females exhibited up to a two-fold increase in ovariole number, with benefits amplified in protein-rich, high-calorie diets. In contrast, resistant males displayed increased testis size but reduced seminal vesicle and accessory gland size, revealing sex-specific trade-offs. Critically, contaminating doses of imidacloprid shifted nutritional optima according to genotype, in some cases enhancing reproduction in susceptible flies, consistent with diet-dependent hormesis. Thus, resistance, nutrient availability and toxin exposure jointly determine fitness outcomes. Our findings demonstrate that resistance evolution is embedded within dietary landscapes rather than driven by toxicity alone, highlighting the need to integrate nutritional ecology into predictions of resistance dynamics in human-modified environments.