Abstract
Nutrition is a primary determinant of health, but responses to nutrition vary with genotype. Epistasis between mitochondrial and nuclear genomes may cause some of this variation, but which mitochondrial loci and nutrients participate in complex gene-by-gene-by-diet interactions? Furthermore, it remains unknown whether mitonuclear epistasis is involved only in the immediate responses to changes in diet, or whether mitonuclear genotype might modulate sensitivity to variation in parental nutrition, to shape intergenerational fitness responses. Here, in Drosophila melanogaster, we show that mitonuclear epistasis shapes fitness responses to variation in dietary lipids and amino acids. We also show that mitonuclear genotype modulates the parental effect of dietary lipid and amino acid variation on offspring fitness. Effect sizes for the interactions between diet, mitogenotype, and nucleogenotype were equal to or greater than the main effect of diet for some traits, suggesting that dietary impacts cannot be understood without first accounting for these interactions. Associating phenotype to mtDNA variation in a subset of populations implicated a C/T polymorphism in mt:lrRNA, which encodes the 16S rRNA of the mitochondrial ribosome. This association suggests that directionally different responses to dietary changes can result from variants on mtDNA that do not change protein coding sequence, dependent on epistatic interactions with variation in the nuclear genome.
Funder
German federal and state governments
Medical Research Council
University of Glasgow
Deutsche Forschungsgemeinschaft
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Reference73 articles.
1. Genotype-by-Diet Interactions Drive Metabolic Phenotype Variation in Drosophila melanogaster;LK Reed;Genetics,2010
2. Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening;C-Y Liao;Aging Cell,2009
3. The Nature of Nutrition: A Unifying Framework from Animal Adaptation to Human Obesity;SJ Simpson,2012
4. An Expanded View of Complex Traits: From Polygenic to Omnigenic;EA Boyle;Cell,2017
5. G×G×E for Lifespan in Drosophila: Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity;C-T Zhu;PLoS Genet,2014
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