ArticlePLoS computational biology2018
Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Reconstructing developmental lineages: a retrospective approach using somatic mutations and variant allele frequency.Frontiers in genetics · 2025Review
- The mutational landscape of the adult healthy parous and nulliparous human breast.Nature communications · 2023Article
- Commonalities and differences in the mutational signature and somatic driver mutation landscape across solid and hollow viscus organs.Oncogene · 2023Review
- Article
- Taking the road less traveled - the therapeutic potential of CBP/β-catenin antagonists.Expert opinion on therapeutic targets · 2021Review
- Somatic Mutations and Autoimmunity.Cells · 2021Review
- Reprogramming enriches for somatic cell clones with small-scale mutations in cancer-associated genes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Rate volatility and asymmetric segregation diversify mutation burden in cells with mutator alleles.Communications biology · 2021Article
- Article
- Cell Fusion-Related Proteins and Signaling Pathways, and Their Roles in the Development and Progression of Cancer.Frontiers in cell and developmental biology · 2021Review
- Inferring evolutionary dynamics of mutation rates through the lens of mutation spectrum variation.Current opinion in genetics & development · 2020Review
- Measuring single cell divisions in human tissues from multi-region sequencing data.Nature communications · 2020Article
- On measuring selection in cancer from subclonal mutation frequencies.PLoS computational biology · 2019Article
- Review
- Mutation-rate plasticity and the germline of unicellular organisms.Proceedings. Biological sciences · 2019Article
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Authors and funding
2 authors.
Funding
Abstract
The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.
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