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

Abstract

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 <i>Drosophila simulans</i> and <i>sechellia</i>, recently diverged species with differential diet choice. <i>D. sechellia</i> larvae, specialized to a nutrient scarce diet, did not survive on sugar-rich conditions, while the generalist species <i>D. simulans</i> was sugar tolerant. Sugar tolerance in <i>D. simulans</i> 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 <i>D. simulans</i> that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as <i>PPP1R15</i>/<i>Gadd34</i> and <i>SERCA</i>, which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition.