Mitochondrial epigenetics and ORFan genes: exploiting the mitochondrial genetic system to fuel phenotypic variation and functional novelties

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Organisms respond to environmental factors over time in two ways: (i) short-term changes during their lifetime (e.g. epigenetic modifications and gene expression changes) and (ii) long-term changes across generations, i.e. heritable evolutionary responses, resulting in genetically distinct populations - potentially even new species. While empirical examples of rapid responses and evolutionary adaptations involving nuclear epigenetic variation (in the form of DNA methylation) and genetic variation (through the evolution of lineage-specific or adaptive genes or ORFan genes) exist from a range of animals and plants, the importance of mitochondria (the powerhouse of cells) and their genomes (mtDNA) in promoting adaptation to both short- and long-term environmental changes using the same mechanisms is still largely unexplored. This major knowledge gap is surprising given the pivotal role of mitochondria in cell survival and functions, aging and human diseases. The proposed research will address this fundamental knowledge gap in our understanding of adaptation and speciation processes through the use an integrative approach combining epigenomics, transcriptomics, physiology and cell biology to investigate the capacity of mitochondria and their genomes to adapt to changing environments. This proposal builds on results from my previous Discovery Grant on the molecular mechanisms underlying doubly uniparental inheritance (DUI) of mitochondria and sex determination in bivalves, which suggested that bivalves likely exploit the mitochondrial genetic system to fuel phenotypic variation and evolutionary innovations. The proposal still focus on bivalves with DUI but also on two model organisms used to study human health and diseases (yeast and planarians). I propose four short-term objectives: 1) measure the mitochondrial epigenetic response to environmental changes; 2) measure the functional consequences of mitochondrial epigenetic variation; 3) estimate the prevalence of mtORFans; and 4) and test their function(s). In objectives 1-2, planarians and bivalves will offer unique opportunities to study mitochondrial epigenetic and transcriptional changes under diverse environmental regimes respectively because of their absence of genetic variation (asexual reproduction in planarians) and the presence of two different mtDNAs in the same nuclear background (DUI). In objectives 3-4, bivalves, with their sex-specific mt-encoded proteins with (still unknown) functions other than energy production, and yeast (S. cerevisiae), with their important mitochondrial genome size, will offer unique opportunities to test the hypothesis that like the nuclear DNA, the mtDNA possesses several overlooked small protein-coding genes that have key functions and are important sources of functional novelty. The questions posited in the current proposal are unique and exciting, and have the potential for transforming our understanding of the role of mitochondria in living organisms.