The causes of mutation accumulation in mitochondrial genomes

Abstract

A fundamental observation across eukaryotic taxa is that mitochondrial genomes have a higher load of deleterious mutations than nuclear genomes. Identifying the evolutionary forces that drive this difference is important to understanding the rates and patterns of sequence evolution, the efficacy of natural selection, the maintenance of sex and recombination and the mechanisms underlying human ageing and many diseases. Recent studies have implicated the presumed asexuality of mitochondrial genomes as responsible for their high mutational load. We review the current body of knowledge on mitochondrial mutation accumulation and recombination, and conclude that asexuality, per se, may not be the primary determinant of the high mutation load in mitochondrial DNA (mtDNA). Very little recombination is required to counter mutation accumulation, and recent evidence suggests that mitochondrial genomes do experience occasional recombination. Instead, a high rate of accumulation of mildly deleterious mutations in mtDNA may result from the small effective population size associated with effectively haploid inheritance. This type of transmission is nearly ubiquitous among mitochondrial genomes. We also describe an experimental framework using variation in mating system between closely related species to disentangle the root causes of mutation accumulation in mitochondrial genomes.

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

“…Notably, recent electron microscopic studies have revealed the presence of abundant four-way and three-way junctions suggestive of recombination intermediates in the oxyradical-rich human adult heart and brain mitochondria (62)(63)(64). A low level of recombination, which is probably limited between intranucleoidal mtDNA molecules (65), may be in place in animal mitochondria from specific tissues as an effective mechanism for mutational clearance while minimizing the invasion by selfish DNAs (66). RecA orthologs have been identified in plant mitochondria (67).…”

Mitonuclear coevolution as the genesis of speciation and the mitochondrial DNA barcode gap

“…Divergent mitonuclear coevolution is inevitable whenever populations are isolated because the nonrecombining and haploid genomes of mitochondria are subject to high mutation rates in metazoans (Lynch 2010). As a consequence, slightly deleterious mutations perpetually accumulate in the mitochondrial genome (Lynch and Blanchard 1998; Neiman and Taylor 2009), and because all mitochondrial genes code for OXPHOS function, an accumulation of deleterious mutations in the mitochondrial genome erodes OXPHOS function resulting in loss of fitness (Wallace 2010). Growing evidence suggests that N‐mt genes can evolve so as to compensate for the deleterious effects of mutations in mt genes, thereby reversing deterioration of OXPHOS (Mishmar et al.…”

Impaired quality control of mitochondria: Aging from a new perspective

“…In mtDNA the mutation rate is considerably higher than in nuclear DNA. Several reasons for this have been put forward including higher ROS levels, reduced DNA repair mechanisms, altered chromatin packaging due to the lack of histones, and a high degree and asymmetry of mtDNA replication (Neiman and Taylor, 2009;Richter et al, 1988). Therefore, mutational damage accumulates more rapidly in mtDNA compared to nuclear DNA leading to dysfunctional proteins and defects in the respiratory chain (Cottrell et al, 2001;Fayet et al, 2002;Muller-Hocker, 1989).…”