Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year

PurposeTuberculosis (TB) remains a significant global health concern, necessitating effective measures to control the epidemic. Understanding the evolution of Mycobacterium tuberculosis (M. tb) through molecular clock analysis is crucial for tracing outbreaks, managing transmission, and ultimately i...

Full description

Saved in:
Bibliographic Details
Main Authors: Jun-Li Wang, Ya-Li Chen, Cui-Ping Guan, Kan Yu, Mao-Shui Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591792/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850158518376595456
author Jun-Li Wang
Jun-Li Wang
Jun-Li Wang
Ya-Li Chen
Cui-Ping Guan
Kan Yu
Kan Yu
Kan Yu
Mao-Shui Wang
author_facet Jun-Li Wang
Jun-Li Wang
Jun-Li Wang
Ya-Li Chen
Cui-Ping Guan
Kan Yu
Kan Yu
Kan Yu
Mao-Shui Wang
author_sort Jun-Li Wang
collection DOAJ
description PurposeTuberculosis (TB) remains a significant global health concern, necessitating effective measures to control the epidemic. Understanding the evolution of Mycobacterium tuberculosis (M. tb) through molecular clock analysis is crucial for tracing outbreaks, managing transmission, and ultimately improving TB management in practice.ResultsA total of 27 studies were included for analysis. The pooled mutation rate was estimated at 0.63 single nucleotide polymorphisms (SNPs) per genome per year [95% confidence interval (CI): 0.51–0.75; 95% predictive interval (PI): 0.04–1.22], significant heterogeneity (I2 = 92.7%, p < 0.001) was observed. Clinical strains had a mutation rate of 0.55 SNPs per year (95% CI: 0.45–0.65; 95% PI: 0.12–0.98), while model strains showed a higher rate of 1.14 SNPs per year (95% CI: 0.68–1.60; 95% PI: −0.22-2.50; Meta-regression analysis, p = 0.006). Mutation rates did not significantly differ between transmission events and reactivation or single episodes (p = 0.497).ConclusionThe mutation rate of clinical M. tb strains is below 1 SNP per genome per year, indicating evolutionary stability in clinical settings. This finding is important for TB outbreak reconstructions and public health strategies. Future research should refine subgroup analyses based on infection characteristics for more precise molecular clock estimates.Systematic review registrationPROSPERO, identifier CRD42024595161.
format Article
id doaj-art-b3cf3baa3e6c4de18b232db91e5c94a3
institution OA Journals
issn 1664-302X
language English
publishDate 2025-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj-art-b3cf3baa3e6c4de18b232db91e5c94a32025-08-20T02:23:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.15917921591792Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per yearJun-Li Wang0Jun-Li Wang1Jun-Li Wang2Ya-Li Chen3Cui-Ping Guan4Kan Yu5Kan Yu6Kan Yu7Mao-Shui Wang8Department of Lab Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, ChinaGuangxi Engineering Research Center for Precise Genetic Testing of Long-Dwelling Nationalities, Guangxi, ChinaEngineering Research Center of Guangxi Higher Education Institutions for Precise Genetic Testing of Long-Dwelling Nationalities, Guangxi, ChinaDepartment of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, ChinaDepartment of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, ChinaMarshall Centre, Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, WA, AustraliaThe Marshall Centre for Infectious Diseases, Research and Training, The University of Western Australia, Perth, WA, AustraliaSchool of Biomedical Sciences, The University Western Australia, Perth, WA, AustraliaDepartment of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, ChinaPurposeTuberculosis (TB) remains a significant global health concern, necessitating effective measures to control the epidemic. Understanding the evolution of Mycobacterium tuberculosis (M. tb) through molecular clock analysis is crucial for tracing outbreaks, managing transmission, and ultimately improving TB management in practice.ResultsA total of 27 studies were included for analysis. The pooled mutation rate was estimated at 0.63 single nucleotide polymorphisms (SNPs) per genome per year [95% confidence interval (CI): 0.51–0.75; 95% predictive interval (PI): 0.04–1.22], significant heterogeneity (I2 = 92.7%, p < 0.001) was observed. Clinical strains had a mutation rate of 0.55 SNPs per year (95% CI: 0.45–0.65; 95% PI: 0.12–0.98), while model strains showed a higher rate of 1.14 SNPs per year (95% CI: 0.68–1.60; 95% PI: −0.22-2.50; Meta-regression analysis, p = 0.006). Mutation rates did not significantly differ between transmission events and reactivation or single episodes (p = 0.497).ConclusionThe mutation rate of clinical M. tb strains is below 1 SNP per genome per year, indicating evolutionary stability in clinical settings. This finding is important for TB outbreak reconstructions and public health strategies. Future research should refine subgroup analyses based on infection characteristics for more precise molecular clock estimates.Systematic review registrationPROSPERO, identifier CRD42024595161.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591792/fullmolecular clockMycobacterium tuberculosissingle nucleotide polymorphismheterogeneitysystematic review
spellingShingle Jun-Li Wang
Jun-Li Wang
Jun-Li Wang
Ya-Li Chen
Cui-Ping Guan
Kan Yu
Kan Yu
Kan Yu
Mao-Shui Wang
Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
Frontiers in Microbiology
molecular clock
Mycobacterium tuberculosis
single nucleotide polymorphism
heterogeneity
systematic review
title Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
title_full Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
title_fullStr Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
title_full_unstemmed Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
title_short Clinical Mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 SNP per genome per year
title_sort clinical mycobacterium tuberculosis isolates exhibit a molecular clock rate below 1 snp per genome per year
topic molecular clock
Mycobacterium tuberculosis
single nucleotide polymorphism
heterogeneity
systematic review
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591792/full
work_keys_str_mv AT junliwang clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT junliwang clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT junliwang clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT yalichen clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT cuipingguan clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT kanyu clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT kanyu clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT kanyu clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear
AT maoshuiwang clinicalmycobacteriumtuberculosisisolatesexhibitamolecularclockratebelow1snppergenomeperyear