ArticleNature ecology & evolution2024
Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout ageing.
Article in Nature ecology & evolution, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Article
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- Non-B DNA structures and their contributions to genetic diversity, aging, and disease.Nucleic acids research · 2026Review
- Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to anti-EGFR therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- The role of mitotype variation and positive epistasis in trait differences between Saccharomyces species.Genetics · 2026Article
- How and why does aging occur? Updating evolutionary theory to meet a new era of data.Evolution, medicine, and public health · 2026Article
- Evolutionary insights intoIMA fungus · 2026Article
- Detection of mutations: from Ames test to duplex sequencing.Frontiers in molecular biosciences · 2026Review
- Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging.Nature aging · 2025Article
- Mechanistic insights into CDCA gene family-mediated glioblastoma progression: implications for diagnosis, prognosis, and therapeutic targeting.Hereditas · 2025Article
- Revisiting the Role of Mitochondrial DNA Mutations in Aging: Bridging Theoretical Expectations with Empirical Observations.Aging and disease · 2025Review
- Mitochondrial Ribosomal Proteins and Cancer.Medicina (Kaunas, Lithuania) · 2025Review
- Mitochondria: fundamental characteristics, challenges, and impact on aging.Biogerontology · 2024Review
- Are some mutations more equal than others?eLife · 2023Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mitochondrial genome in different tissues throughout ageing. We used ultrasensitive duplex sequencing to profile ~2.5 million mitochondrial genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloguing ~1.2 million mitochondrial somatic and ultralow-frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the light strand origin of replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared with primates with a surfeit of reactive oxygen species-associated G > T/C > A mutations, and that somatic mutations in protein-coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that 're-align' mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.
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