Diet’s impact dictated by synonymous mitochondrial SNP interacting with nucleotype

Abstract

Animals vary genetically in responses to dietary change. Both mitochondrial and nuclear genomes contribute to this variation, but the role of combinatorial "mito-nuclear" genetic variation is understudied. We do not know whether specific nutrients modify patterns of mito-nuclear variation, nor whether putative epigenetic mechanisms play a role. Here, we show that enriching dietary essential amino acids or lipids modifies patterns of mito-nuclear variation in Drosophila life-history, including transgenerational effects of lipids. Systematically evaluating alternative statistical models revealed that diet-mito-nuclear interactions were a leading driver of phenotypic variation. Mito-nuclear genotype repeatably predicted phenotypic impacts of nutritional changes, but genotypes bearing naturally co-occurring pairs of mitochondria and nuclei did not necessarily outperform novel pairings, suggesting that nutrition-dependent phenotypes cannot easily be optimised by matching mitochondria to coincident nuclear genotypes. These results enhance understanding of how nutrition and genetics sculpt phenotype, with potential implications for human mitochondrial transfer therapies.

Mitonuclear interactions modulate nutritional preference

“…These studies include Zhu et al [10], where authors found mitonuclear interactions impacted ageing under caloric restriction, with certain mitonuclear genotypes being more impacted than others. More recently, Dobson et al [38] demonstrated that parental effects of dietary lipid and amino acid variation on offspring fitness is modulated by mitonuclear interactions. Furthermore, Aw et al [17] examined how mitonuclear interactions shaped metabolic flexibility to diet, with certain genetic combinations constraining metabolism on certain nutrients.…”

Larval protein restriction interacts with adult diet to increase fitness in an outbred multiparent population

“…The number of offspring produced can be a function of lifespan, underpinning the quality of somatic tissue maintenance. Much research continues to focus on intergenerational effects of variations in nutritional supply and quality on offspring development and fitness [4,13,14]. Thus, we now appreciate that poor maternal conditions can limit offspring development through poor provisioning and care of eggs and juveniles [15].…”