Abstract

Historically, mtDNA was considered a selectively neutral marker that was useful for estimating the population genetic history of the maternal lineage. Over time there has been an increasing appreciation of mtDNA and mitochondria in maintaining cellular and organismal health. Beyond energy production, mtDNA and mitochondria have critical cellular roles in signalling. Here we briefly review the structure of mtDNA and the role of the mitochondrion in energy production. We then discuss the predictions that can be obtained from quaternary structure modelling and focus on mitochondrial complex I. Complex I is the primary entry point for electrons into the electron transport system is the largest respiratory complex of the chain and produces about 40% of the proton flux used to synthesize ATP. A focus of the review is Drosophila’s utility as a model organism to study the selective advantage of specific mutations. However, we note that the incorporation of insights from a multitude of systems is necessary to fully understand the range of roles that mtDNA has in organismal fitness. We speculate that dietary changes can illicit stress responses that influence the selective advantage of specific mtDNA mutations and cause spatial and temporal fluctuations in the frequencies of mutations. We conclude that developing our understanding of the roles mtDNA has in determining organismal fitness will enable increased evolutionary insight and propose we can no longer assume it is evolving as a strictly neutral marker without testing this hypothesis.

摘要

从历史上看，mtDNA被认为是选择性中性标记，可用于评估母系谱系的群体遗传史。随着时间的流逝，在维持细胞和机体健康方面，对mtDNA和线粒体有了越来越多的了解。除了产生能量以外，mtDNA和线粒体在信号传导中也起着至关重要的细胞作用。在这里，我们简要回顾了mtDNA的结构以及线粒体在能源生产中的作用。然后，我们讨论可以从四级结构建模获得的预测，并集中于线粒体复合体I。复合体I是电子进入电子传输系统的主要入口点，是链中最大的呼吸复合体，并产生约40％的质子用于合成ATP的助焊剂。审查的重点是果蝇作为研究特定突变的选择性优势的模式生物的工具。但是，我们注意到，要充分了解mtDNA在机体适应性中的作用范围，有必要整合来自多个系统的见解。我们推测饮食结构的变化会导致非法的应激反应，从而影响特定mtDNA突变的选择性优势，并导致突变频率的时空波动。我们得出结论，对mtDNA在确定机体适应性中的作用有了进一步的了解，将能够增加进化的见解，并建议我们在不检验该假设的情况下就不能再假设它正在发展为严格的中性标记。