Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis.

How dietary selection affects genome evolution to define the optimal range of nutrient intake is a poorly understood question with medical relevance. We have addressed this question by analyzing and , recently diverged species with differential diet choice. larvae, specialized to a nutrient scarce diet, did not survive on sugar-rich conditions, while the generalist species was sugar tolerant. Sugar tolerance in was a tradeoff for performance on low-energy diet and was associated with global reprogramming of metabolic gene expression. Hybridization and phenotype-based introgression revealed the genomic regions of that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as / and , which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition.