ArticleNucleic acids research2020
MtDNA sequence features associated with 'selfish genomes' predict tissue-specific segregation and reversion.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Optimal Organelle Inheritance Strategies Under Different Changing Environments and Mutational Pressures.Genome biology and evolution · 2026Article
- Comparative synthesis of tandem repeats in the control region of Epinephelus mitogenomes (Peciformes: Epinephelidae).Genetics and molecular biology · 2026Article
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- Mitochondrial DNA Mutations in Colorectal Cancer Stem Cells: Implications for Tumor Dynamics and Therapeutic Strategies.Current medicinal chemistry · 2026Review
- Mitochondrial Genome Instability inBiology · 2024Article
- Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes in Caenorhabditis elegans.Nature communications · 2024Article
- Dissecting the sequential evolution of a selfish mitochondrial genome in Caenorhabditis elegans.Heredity · 2024Article
- Evolution and maintenance of mtDNA gene content across eukaryotes.The Biochemical journal · 2024Review
- Mitochondrial DNAFrontiers in ophthalmology · 2023Article
- Article
- Sorting of mitochondrial and plastid heteroplasmy inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mutational profiling of mtDNA control region reveals tumor-specific evolutionary selection involved in mitochondrial dysfunction.EBioMedicine · 2022Article
- Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson's Disease.Genes · 2021Review
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA (mtDNA) encodes cellular machinery vital for cell and organism survival. Mutations, genetic manipulation, and gene therapies may produce cells where different types of mtDNA coexist in admixed populations. In these admixtures, one mtDNA type is often observed to proliferate over another, with different types dominating in different tissues. This 'segregation bias' is a long-standing biological mystery that may pose challenges to modern mtDNA disease therapies, leading to substantial recent attention in biological and medical circles. Here, we show how an mtDNA sequence's balance between replication and transcription, corresponding to molecular 'selfishness', in conjunction with cellular selection, can potentially modulate segregation bias. We combine a new replication-transcription-selection (RTS) model with a meta-analysis of existing data to show that this simple theory predicts complex tissue-specific patterns of segregation in mouse experiments, and reversion in human stem cells. We propose the stability of G-quadruplexes in the mtDNA control region, influencing the balance between transcription and replication primer formation, as a potential molecular mechanism governing this balance. Linking mtDNA sequence features, through this molecular mechanism, to cellular population dynamics, we use sequence data to obtain and verify the sequence-specific predictions from this hypothesis on segregation behaviour in mouse and human mtDNA.
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