ArticleGenome biology and evolution2013
Functional recurrent mutations in the human mitochondrial phylogeny: dual roles in evolution and disease.
Article in Genome biology and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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47 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
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- Analysis of Selective Pressure on Ancient Human Mitochondrial Genomes Reveals the Presence of Widespread Sequencing Artefacts.International journal of molecular sciences · 2025Article
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- Maternally Inherited Essential Hypertension May Be Associated with the Mutations in Mitochondrial tRNAPharmacogenomics and personalized medicine · 2024Article
- The metazoan landscape of mitochondrial DNA gene order and content is shaped by selection and affects mitochondrial transcription.Communications biology · 2023Article
- Maternally transmitted diabetes mellitus may be associated with mitochondrial ND5 T12338C and tRNAIrish journal of medical science · 2022Article
- Human mitochondrial RNA modifications associate with tissue-specific changes in gene expression, and are affected by sunlight and UV exposure.European journal of human genetics : EJHG · 2022Article
- Mitochondrial tRNAGln 4394C>T Mutation May Contribute to the Clinical Expression of 1555A>G-Induced DeafnessGenes · 2022Article
- Helena's Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample.International journal of molecular sciences · 2022Article
- Clinical and molecular features of two diabetes families carrying mitochondrial ND1 T3394C mutation.Irish journal of medical science · 2022Article
- Maternally transmitted nonsyndromic hearing impairment may be associated with mitochondrial tRNAJournal of clinical laboratory analysis · 2022Article
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- Mitochondrial DNA haplogroup analysis in Saudi Arab patients with multiple sclerosis.PloS one · 2022Article
- Contribution of mitochondrial gene variants in diabetes and diabetic kidney disease.Frontiers in endocrinology · 2022Article
- Mitochondrial Diabetes is Associated with tRNADiabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations frequently reoccur in the human mitochondrial DNA (mtDNA). However, it is unclear whether recurrent mtDNA nodal mutations (RNMs), that is, recurrent mutations in stems of unrelated phylogenetic nodes, are functional and hence selectively constrained. To answer this question, we performed comprehensive parsimony and maximum likelihood analyses of 9,868 publicly available whole human mtDNAs revealing 1,606 single nodal mutations (SNMs) and 679 RNMs. We then evaluated the potential functionality of synonymous, nonsynonymous and RNA SNMs and RNMs. For synonymous mutations, we have implemented the Codon Adaptation Index. For nonsynonymous mutations, we assessed evolutionary conservation, and employed previously described pathogenicity score assessment tools. For RNA genes' mutations, we designed a bioinformatic tool which compiled evolutionary conservation and potential effect on RNA structure. While comparing the functionality scores of nonsynonymous and RNA SNMs and RNMs with those of disease-causing mtDNA mutations, we found significant difference (P < 0.001). However, 24 RNMs and 67 SNMs had comparable values with disease-causing mutations reflecting their potential function thus being the best candidates to participate in adaptive events of unrelated lineages. Strikingly, some functional RNMs occurred in unrelated mtDNA lineages that independently altered susceptibility to the same diseases, thus suggesting common functionality. To our knowledge, this is the most comprehensive analysis of selective signatures in the mtDNA not only within proteins but also within RNA genes. For the first time, we discover virtually all positively selected RNMs in our phylogeny while emphasizing their dual role in past evolutionary events and in disease today.
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