PT  - JOURNAL ARTICLE
AU  - Hoekstra, Luke A.
AU  - Julick, Cole R.
AU  - Mika, Katelyn M.
AU  - Montooth, Kristi L.
TI  - Energy demand and the context-dependent effects of genetic interactions
AID  - 10.1101/209510
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 209510
4099  - http://biorxiv.org/content/early/2017/10/26/209510.short
4100  - http://biorxiv.org/content/early/2017/10/26/209510.full
AB  - 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 photoperiod 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 generally result from variation in energy demand. The effects of this genotype also differ across life stages and between the sexes. The mitochondrial-nuclear genetic interaction disrupts metabolic rate in growing larvae, but not in adults, and compromises female, but not male, reproductive fitness. 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.IMPACT SUMMARY Genetic effects on traits are often context dependent, such that a genotype that improves fitness under one context may have no effect or even a deleterious effect in another context. The external environment is a common context that affects the degree to which a genotype determines a phenotype, but the internal environment of an organism (e.g., its genetic background, sex or life stage) also provides an important context that may modify the phenotypic expression of a genotype. Here we combine new data on the phenotypic effects of a well-characterized genetic interaction between the mitochondrial and nuclear genomes of the fruit fly Drosophila with prior observations to support a model of energy demand as a general explanation for context-dependent genetic effects, particularly for mutations that affect metabolism. We show that the magnitude of fitness effects of this genetic interaction correlates positively with the degree of energy demand among developmental treatments that accelerate growth rate, across developmental stages that differ in the cost of growth, and between sexes with potentially different costs of reproduction. These internal and external contexts create variable demands on energy metabolism that will impact the efficacy of natural selection acting on metabolic mutations in populations.