Abstract

Metabolic effects of genetic variation often depend on diet, yet the loci underlying diet-dependent developmental responses remain incompletely defined. Here we combine multi-trait phenotyping of Drosophila Genetic Reference Panel lines with genome-wide mapping in newly developed Drosophila Recombinant Populations. High sugar causes genotype- and life-stage-dependent changes in metabolic and life-history traits, with development time emerging as a highly heritable, sugar-sensitive phenotype. Mapping in 16 outbred advanced intercross populations reveals distinct association landscapes under low- and high-sugar diets, with a concentrated low-sugar signal, a more distributed high-sugar pattern, and identified genotype-by-diet loci including tap, Eip75B and Cerk. Functional perturbation supports diet-dependent effects for several prioritized candidates. Allele-frequency analyses identify operationally defined thrifty-like variants associated with delayed development under high sugar and relatively earlier development under low sugar; these variants are enriched for cell-adhesion, neurodevelopmental, and morphogenetic processes. Together, these results establish an outbred Drosophila framework for dissecting how dietary sugar remodels the genetic architecture of development time.