bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–12–07
two papers selected by
Mariangela Santorsola, Università di Pavia



  1. Ecol Evol. 2025 Dec;15(12): e72603
      Allopatric divergence can result in the evolution of incomplete reproductive barriers, which are put to the test when species come into secondary contact. North American red-backed voles (Clethrionomys rutilus, C. gapperi) form a broad contact zone, presenting an opportunity to investigate outcomes of secondary contact. Using RADseq data for > 200 red-backed vole specimens across three transects of the contact zone (Southeast Alaska, British Columbia, Northwest Territories), we test for evidence of admixture and describe the biogeographic history of each region. We find limited evidence for nuclear admixture, but by analyzing nuclear and mitochondrial RAD loci separately, we detect extensive unidirectional mitochondrial introgression. In British Columbia, the pattern of mitonuclear discordance is consistent with a moving hybrid zone, and suggests the possibility of adaptive mitochondrial introgression. In Southeast Alaska, mitochondrial introgression is localized to a smaller geographic region, and involves a distinct C. rutilus mitochondrial haplotype that is only found in specimens with C. gapperi nuclear genomes. In contrast, we find no evidence for mitochondrial introgression in the Northwest Territories. Together, our results suggest a complex biogeographic history for North American red-backed voles, mediated by the availability of ice-free colonization pathways following the LGM and incomplete barriers to reproduction, leading to different outcomes of secondary contact across the continent.
    Keywords:  biogeography; hybridization; mitochondrial introgression; mitonuclear discordance; red‐backed voles
    DOI:  https://doi.org/10.1002/ece3.72603
  2. Nat Commun. 2025 Dec 02.
    NHLBI Trans-Omics for Precision Medicine (TOPMed) mtDNA Working Group
      We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we introduce a truncating mtDNA mutation (MT-COX3, mt.9979) and observe a positive correlation between variant allele fraction and methylation at cg04569152, supporting a direct mtDNA-nDNA epigenetic link. Many heteroplasmy-associated CpGs overlap with known methylation-trait associations for metabolic and behavioral traits. Composite CpG scores predict all-cause mortality and incident CVD, with one-unit increases associated with 1.27-fold and 1.12-fold higher hazards, respectively. These findings suggest an mtDNA-nDNA epigenetic connection in aging and disease, though its direction and mechanisms remain to be studied.
    DOI:  https://doi.org/10.1038/s41467-025-65845-2