Wolff Jonci N, Ladoukakis Emmanuel D, Enríquez José A, Dowling Damian K
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
Department of Biology, University of Crete, 70013 Heraklion, Crete, Greece.
Philos Trans R Soc Lond B Biol Sci. 2014 Jul 5;369(1646):20130443. doi: 10.1098/rstb.2013.0443.
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.
基本生物学过程取决于跨越两个必需基因组（线粒体基因组和核基因组）的基因之间的协调相互作用。这些相互作用是复杂生命的关键，因此，在参与这种基因组间相互作用的基因座上积累并持续存在的等位基因变异应受到强烈选择，以维持线粒体电子传递系统的完整性。在这里，我们汇总了证据，表明线粒体 - 核（线粒体 - 核）等位基因相互作用在几个生物学尺度上，即物种内（种群内和种群间）以及物种间，是关键健康相关和生活史表型表达的具有进化意义的调节因子。然后，我们介绍了线粒体 - 核相互作用研究的一个新前沿——那些发生在个体内部，并由线粒体DNA异质性以及核编码的线粒体基因重复和异构体的存在所驱动的相互作用。经验证据支持对个体内部线粒体 - 核相互作用进行高分辨率组织和环境特异性调节的观点。预测线粒体DNA诱导的线粒体疾病的外显率、严重程度和表达模式仍然是一个难题。我们认为，更深入地了解线粒体 - 核相互作用在所有生物学层面的动态和影响，将提供关键见解，切实推进我们不仅对核心进化过程的理解，而且对人类线粒体疾病潜在复杂遗传学的理解。
