Evolutionary mismatch between nuclear and mitochondrial genomes does not promote reversion mutations in mtDNA.

Abstract

Serrano et al. (Serrano et al., 2024) use a high-fidelity somatic mtDNA mutation analysis in conplastic mice in which mtDNA was replaced with exogenous mtDNA of different mouse strains. Serrano reported apparent abundant somatic reversion mutations in the exogenous mtDNA that seemed to restore the original mito-nuclear match. If real, such a phenomenon would have important implications for health and genetics. In todays highly mixed human population, the pairing of potentially mismatched nuclear and mitochondrial genomes is widespread, so the proposed reversion mutagenesis should be commonplace. We demonstrate, however, that these reversion mutations are not real but originate from cross-contamination between samples and from NUMTs, the mtDNA pseudogenes located in the nuclear genome.