bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–11–16
three papers selected by
Mariangela Santorsola, Università di Pavia



  1. Mol Biol Evol. 2025 Nov 11. pii: msaf291. [Epub ahead of print]
      Metazoan oxidative phosphorylation (OXPHOS) complexes are composed of subunits encoded by mitochondrial and nuclear genes, requiring continuous mitonuclear coevolution to ensure functional compatibility. However, mitochondrial and nuclear genomes exhibit separate inheritance patterns, leading to their distinct or even conflicting evolutionary histories. This study aimed to analyse phylogenetic signals among mitochondrial genes, nuclear-encoded OXPHOS genes, and general nuclear genes across 53 beetle species. Two major cases of mitonuclear discordance were detected. The nuclear-encoded OXPHOS genes supported mitochondrial phylogenetic signals in noterids, indicating that in noterids the evolutionary history of OXPHOS complexes diverged from the phylogenetic history. Conversely, nuclear-encoded OXPHOS genes aligned with the phylogenetic history of rhysodines, and this mitonuclear discordance suggests that mitochondrial genomes exhibited clear signatures of genetic introgression. By integrating phylogenetic reconstructions and reticulate evolutionary network analyses, we attributed the mitonuclear discordance in noterids to incomplete lineage sorting. In contrast, the mitochondrial genomes of rhysodines underwent introgressive hybridization events. Although mitonuclear incompatibility is typically resolved by nuclear compensatory mechanisms, our findings indicate that nuclear compensation exhibits limited efficacy at the gene level, yet locally adaptive residues persist. This was further supported by the weak correlation between nuclear-encoded OXPHOS genes and mitochondrial genes, with no robust mitonuclear coevolutionary signals detected. These findings collectively suggest a loose mitonuclear interaction in beetles. The decoupling of mitochondrial and nuclear evolutionary trajectories may serve as an evolutionary 'buffer' to accommodate genomic conflicts while maintaining essential OXPHOS systems.
    Keywords:  Adephaga; OXPHOS; mitochondrial introgression; mitonuclear discordance; nuclear compensation
    DOI:  https://doi.org/10.1093/molbev/msaf291
  2. IMA Fungus. 2025 ;16 e165520
      Mitonuclear interactions are crucial in governing mitochondrial function, development and responses to stress in eukaryotic organisms. In this study, we explored how varying mitochondrial haplotypes affect the phenotype and oxidative stress response using hybrids of the basidiomycete Pleurotus ostreatus (P. ostreatus) as a model system. By performing reciprocal crosses between monokaryotic strains with distinct nuclear and mitochondrial genomes, we identified notable differences in growth rates, accumulation of reactive oxygen species (ROS) and gene expression patterns. Hybrids with incompatible mitonuclear combinations displayed slower growth and elevated expression of genes - some showing transgressive inheritance - associated with the Electron Transport Chain (ETC) and antioxidant defences. Mitochondria-dependent heterosis was observed in hybrids sharing the same nuclear background, but differing in mitochondrial genome, suggesting that mitonuclear incompatibilities can result in oxidative imbalance and compromised fungal performance. This experimental approach opens wide possibilities for exploring mitonuclear interactions and highlights the significance of mitonuclear co-adaptation in an edible mushroom, offering valuable insights for enhancing hybrid breeding programmes by accounting for the role of mitonuclear interactions in shaping quantitative traits related to mushroom yield.
    Keywords:  Electron transport chain; hybrid breakdown; mitochondrial dysfunction; mitonuclear incompatibility; oxidative stress
    DOI:  https://doi.org/10.3897/imafungus.16.165520
  3. Genomics Proteomics Bioinformatics. 2025 Nov 05. pii: qzaf098. [Epub ahead of print]
      Dysfunctional mitochondria are implicated in various diseases, however comprehensive characterization of mitochondrial DNA (mtDNA) in the Chinese population remains limited. Here, we conducted a systematic analysis of mtDNA from 7331 samples, comprising 4129 Chinese samples (NyuWa) and 3202 samples from the 1000 Genomes Project (1KGP). We identified 7216 distinct high-quality mtDNA variants, classified them into 22 macro-haplogroups, and detected 1466 distinct nuclear mitochondrial DNA segments (NUMTs). Among these, 88 mtDNA variants and 642 NUMTs were specific to NyuWa. Genome-wide association analyses revealed significant correlations between 12 mtDNA variants and 199 nuclear DNA (nDNA) variants. Our findings demonstrated that all individuals in both NyuWa and 1KGP harbored common NUMTs, while one-fifth possessed ultra-rare NUMTs that tended to insert into nuclear gene regions. Notably, rare NUMTs in the NyuWa cohort showed significant enrichment of nuclear breakpoints in long interspersed nuclear elements (LINEs) compared to 1KGP. Overall, this study provides the first comprehensive profile of NUMTs in the Chinese population and establishes the most extensive resource of Chinese mtDNA variants and NUMTs based on high-depth whole genome sequencing (WGS) to date, providing valuable reference resources for genetic research on mtDNA-related diseases.
    Keywords:  Mitochondrial DNA; NUMTs; Whole genome sequencing; mtDNA variants; mtDNA-nDNA variant association
    DOI:  https://doi.org/10.1093/gpbjnl/qzaf098