Cellular and population level processes influence the rate, accumulation and observed frequency of inherited and somatic mtDNA mutations

Mutagenesis
Richard G Melvin, J William O Ballard

Abstract

Mitochondria are found in all animals and have the unique feature of containing multiple copies of their own small, circular DNA genome (mtDNA). The rate and pattern of mutation accumulation in the mtDNA are influenced by molecular, cellular and population level processes. We distinguish between inherited and somatic mtDNA mutations and review evidence for the often-made assumption that mutations accumulate at a higher rate in mtDNA than in nuclear DNA (nDNA). We conclude that the whole genome mutation accumulation rate is higher for mtDNA than for nDNA but include the caveat that rates overlap considerably between the individual mtDNA- and nDNA-encoded genes. Next, we discuss the postulated causal mechanisms for the high rate of mtDNA mutation accumulation in both inheritance and in somatic cells. Perhaps unexpectedly, mtDNA is resilient to many mutagens of nDNA but is prone to errors of replication. We then consider the influence of maternal inheritance, recombination and selection on the observed accumulation pattern of inherited mtDNA mutations. Finally, we discuss environmental influences of temperature and diet on the observed frequency of inherited and somatic mtDNA mutations. We conclude that it is necessary to understa...Continue Reading

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Citations

Jun 7, 2019·Integrative and Comparative Biology·Wendy R HoodGeoffrey E Hill
Dec 4, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sarah SchaackFenner Macrae
Nov 23, 2017·Frontiers in Oncology·Kate L Hertweck, Santanu Dasgupta
Apr 24, 2021·Genome Biology and Evolution·Sophie BretonLiliana Milani

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