title: Mitonuclear interactions: evolutionary consequences over multiple biological scales.
abstract: Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes--mitochondrial and nuclear. These interactions are key to complex life, and allelic variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial-nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales--within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions--those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, New South Wales, Australia Evolution and Ecology Research Centre, University of New South Wales, Sydney 2052, New South Wales, Australia School of Biological Sciences, Monash University, Clayton 3800, Victoria, Australia jonciwolff@yahoo.com.
authors.forename: Jonci N
authors.initials: JN
authors.lastname: Wolff
authors.affiliation: Department of Biology, University of Crete, 70013 Heraklion, Crete, Greece.
authors.forename: Emmanuel D
authors.initials: ED
authors.lastname: Ladoukakis
authors.affiliation: Regenerative Cardiology Department, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain Departamento de Bioquímica, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Enríquez
authors.affiliation: School of Biological Sciences, Monash University, Clayton 3800, Victoria, Australia damian.dowling@monash.edu.au.
authors.forename: Damian K
authors.initials: DK
authors.lastname: Dowling
mesh_terms: D005075:Biological Evolution; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000502:physiology; D028361:Mitochondrial Diseases / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial
keywords: coevolution; genome conflict; mitochondria; mitochondrial disease; mitonuclear interaction