SYSTEMATIC REVIEW article

Front. Microbiol.

Sec. Infectious Agents and Disease

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1591792

This article is part of the Research TopicReviews in Molecular Evolution of Infectious Agents and DiseasesView all 4 articles

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

Provisionally accepted
Jun-Li  WangJun-Li Wang1Ya-Li  ChenYa-Li Chen2Cui-Ping  GuanCui-Ping Guan2Kan  YuKan Yu3Mao-Shui  WangMao-Shui Wang2*
  • 1Youjiang Medical University for Nationalities, Baise, Guangx, China
  • 2Shandong Public Health Clinical Center, Jinan, China
  • 3University of Western Australia, Perth, Western Australia, Australia

The final, formatted version of the article will be published soon.

Tuberculosis (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.A 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).The 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.

Keywords: molecular clock, Mycobacterium tuberculosis, Single nucleotide polymorphism, heterogeneity, Systematic review

Received: 11 Mar 2025; Accepted: 16 May 2025.

Copyright: © 2025 Wang, Chen, Guan, Yu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mao-Shui Wang, Shandong Public Health Clinical Center, Jinan, China

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