Energy demand and the context-dependent effects of genetic interactions underlying metabolism

Genetic effects are often context-dependent, with the same genotype differentially affecting phenotypes across environments, life stages, and sexes. We used an environmental manipulation designed to increase energy demand during development to investigate energy demand as a general physiological explanation for context-dependent effects of mutations, particularly for those mutations that affect metabolism. We found that increasing the period during which Drosophila larvae are active during development phenocopies a temperature-dependent developmental delay in a mitochondrial-nuclear genotype with disrupted metabolism. This result indicates that the context-dependent fitness effects of this genotype are not specific to the effects of temperature and may result generally from variation in energy demand. The effects of this genotype also differ across life stages and between the sexes. Metabolic rates are disrupted by this genetic interaction in growing larvae, but not in adults; and reproduction of females, but not males, is compromised by this genetic interaction. These patterns are consistent with a model where context-dependent genotype-phenotype relationships may generally arise from differences in energy demand experienced by individuals across environments, life stages, and sexes.