ArticlePLoS pathogens2019
The molecular clock of Mycobacterium tuberculosis.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it.
- ClinicalFrontiers in microbiology · 2025Pooled it
- Comparison of phylogenetic metrics of transmission between symptomatic and asymptomatic tuberculosis in individuals who were incarcerated in Brazil in 2008-24: a retrospective genomic epidemiology study.The Lancet. Microbe · 2026Article
- The Phylodynamic Threshold of Measurably Evolving Populations.Molecular biology and evolution · 2026Article
- Transmission of rifampicin-resistant tuberculosis in Ho Chi Minh City, Viet Nam: a prospective genomic epidemiology study.The Lancet regional health. Western Pacific · 2026Article
- Whole-genome sequencing suggests recent transmission of rifampicin-resistant tuberculosis in Botswana.BMC infectious diseases · 2026Article
- Genomic epidemiology ofMicrobial genomics · 2026Article
- Gene conversion is a key driver of diversity hotspots inbioRxiv : the preprint server for biology · 2026Article
- An ancient Erysipelothrix rhusiopathiae genome recovered from 1400-year-old human remains in the Northern Caucasus.Scientific reports · 2026Article
- Phylodynamic analysis reveals disparate transmission dynamics of Mycobacterium tuberculosis complex lineages in Botswana.Scientific reports · 2025Article
- Subpopulations in clinical samples ofJAC-antimicrobial resistance · 2025Article
- Comparison of phylogenetic metrics of transmission in symptomatic and asymptomatic tuberculosis.medRxiv : the preprint server for health sciences · 2025Article
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Longitudinal phenotypic and genomic evidence revealing increased risk of drug resistance accumulation in tuberculosis patients in the counties of central China.Microbiology spectrum · 2025Article
- UShER-TB: Scalable, Comprehensive, Accessible Phylogenomic Analysis ofmedRxiv : the preprint server for health sciences · 2025Article
- Sociality and kinship constrain the free-mixing of pathogens in a wild mammal host population.Proceedings. Biological sciences · 2025Article
- KPop: accurate and scalable comparative analysis of microbial genomes by sequence embeddings.Genome biology · 2025Article
- Drug Resistance and Epidemiological Success of Modern Mycobacterium tuberculosis Lineages in Western India.The Journal of infectious diseases · 2025Article
- Signatures of transmission in within-host Mycobacterium tuberculosis complex variation: a retrospective genomic epidemiology study.The Lancet. Microbe · 2025Article
- Seamless, rapid, and accurate analyses of outbreak genomic data using splitGenome research · 2024Article
- Whole genome sequencing analysis of Mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines.Scientific reports · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular clock and its phylogenetic applications to genomic data have changed how we study and understand one of the major human pathogens, Mycobacterium tuberculosis (MTB), the etiologic agent of tuberculosis. Genome sequences of MTB strains sampled at different times are increasingly used to infer when a particular outbreak begun, when a drug-resistant clone appeared and expanded, or when a strain was introduced into a specific region. Despite the growing importance of the molecular clock in tuberculosis research, there is a lack of consensus as to whether MTB displays a clocklike behavior and about its rate of evolution. Here we performed a systematic study of the molecular clock of MTB on a large genomic data set (6,285 strains), covering different epidemiological settings and most of the known global diversity. We found that sampling times below 15-20 years were often insufficient to calibrate the clock of MTB. For data sets where such calibration was possible, we obtained a clock rate between 1x10-8 and 5x10-7 nucleotide changes per-site-per-year (0.04-2.2 SNPs per-genome-per-year), with substantial differences between clades. These estimates were not strongly dependent on the time of the calibration points as they changed only marginally when we used epidemiological isolates (sampled in the last 40 years) or three ancient DNA samples (about 1,000 years old) to calibrate the tree. Additionally, the uncertainty and the discrepancies in the results of different methods were sometimes large, highlighting the importance of using different methods, and of considering carefully their assumptions and limitations.
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