Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

陆地植物中的线粒体和质体基因组显示出在任何真核基因组中观察到的某些最慢的序列进化速率，这表明其具有出色的预防或纠正突变的能力。但是，导致这种极端保真的机制仍然不清楚。我们测试了涉及细胞质DNA复制，重组和修复的7个候选基因（POLIA，POLIB，MSH1，RECA3，UNG，FPG和OGG1）对模型被子植物拟南芥中突变率的影响通过应用高度精确的DNA测序技术（双重测序），即使在低异质频率下，也可以检测到新出现的线粒体和质体突变。我们发现破坏MSH1（而不是其他候选基因）会导致点突变和小插入缺失的频率大量增加，并改变线粒体和质体DNA的突变谱。我们还使用液滴数字PCR显示了msh1突变体中新生代在各个世代之间的传播，证实了对可遗传突变率的贡献。该双靶基因是mutS内神秘系的一部分我们发现的错配修复家族也存在于绿色植物以外的多个真核生物群体中（蝶形目，肺泡，触藻类和隐孢子虫），以及某些细菌和病毒。先前已证明MSH1可以限制植物细胞质基因组中的异位重组。我们的结果表明，在识别和纠正植物线粒体和质体DNA序列中的错误中，其作用更为广泛，可能通过基于忠实同源重组的双链断裂和修复途径的启动，大大抑制了突变率。