Journal Article

MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes

Wu, Zhiqiang, King, Connor R., Broz, Amanda K., Waneka, Gus, Sloan, Daniel B.

2020

Overview

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 arisenmitochondrial and plastidmutations 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 lineagewithin the mutS mismatch repair family thatwe 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 doublestranded breaks and repair pathways based on faithful homologous recombination.

• Publisher: National Academy of Sciences
• Subject: Arabidopsis - genetics / Arabidopsis - metabolism / Arabidopsis Proteins - genetics / Arabidopsis Proteins - metabolism / Biological Sciences / Deoxyribonucleic acid / DNA / DNA biosynthesis / DNA repair / DNA sequencing / Gene Expression Regulation, Plant / Genes / Genetics / Genome, Mitochondrial / Genome, Plant / Genome, Plastid / Genomes / Homologous recombination / Homology / Mismatch repair / Mitochondria - genetics / Mitochondria - metabolism / Mitochondrial DNA / Mutation / Mutation Rate / Mutation rates / MutS DNA Mismatch-Binding Protein - genetics / MutS DNA Mismatch-Binding Protein - metabolism / Nucleotide sequence / OGG1 protein / Plastids - genetics / Plastids - metabolism / Repair