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Mitochondria as environments for the nuclear genome in Drosophila: Mitonuclear GxGxE


Rand, David; Mossman, Jim; Spierer, Adam; Santiago, John (2021), Mitochondria as environments for the nuclear genome in Drosophila: Mitonuclear GxGxE, Dryad, Dataset,


Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the two genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (GxG) and gene-by-environment (GxE) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (GxG), and expose these mitonuclear genotypes to altered dietary environments to examine GxE interactions. We use development time and genome wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear GxGxE). We show that the nuclear transcriptional response to alternative mitochondrial ‘environments’ (GXG) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified co-expressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes GxG genes that are concordant with GxE genes, suggesting that mitonuclear interactions are part of an organism’s environment.


Drosophila genotypes were exposed to alternative environments, their RNA was extracted and sequenced and analyses of these data were used to infer the effect of genotype and environment on gene expression profiles.

Usage Notes

Supplementary files with output from these analyses.


National Institute of General Medical Sciences, Award: 2R01GM067862

National Institute of General Medical Sciences, Award: 1R35GM139607