Estimation of molecular clock of Mycobacterium tuberculosis based on whole genome sequencing data.
10.3760/cma.j.cn112338-20220408-00272
- Author:
Bi Lin TAO
1
;
Yu Ting WANG
1
;
Zhong Qi LI
1
;
Ji Zhou WU
1
;
Jian Ming WANG
2
Author Information
1. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
2. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China Department of Epidemiology, Gusu School, Nanjing Medical University, Nanjing 211166, China.
- Publication Type:Journal Article
- MeSH:
Genome, Bacterial;
Humans;
Mycobacterium tuberculosis/genetics*;
Recurrence;
Tuberculosis/microbiology*;
Whole Genome Sequencing
- From:
Chinese Journal of Epidemiology
2022;43(9):1462-1468
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To analyze the genomic mutation of Mycobacterium tuberculosis (M. tuberculosis) isolated in endogenous activation period and estimate the molecular clock based on the whole genome sequencing data. Methods: Literatures of the whole genome research of endogenous reactivated tuberculosis were retrieved, and the corresponding whole genome sequencing data were downloaded. We extracted the single nucleotide polymorphisms (SNPs) and strain isolation time of initial treatment and relapse of tuberculosis cases, explored the relationship between the different SNPs and interval between initial treatment and relapse by Poisson regression model, calculated the M. tuberculosis molecular clock, and estimated the mutation rate. Results: When the generation time of M. tuberculosis was 18 hours, the mutation rate in 0-2 years, i.e. short-term endogenous activation, was 6.47×10-10 (95%CI: 5.59×10-10-7.44×10-10), which was significantly higher than that in 2-14 years in long term endogenous activation (3.27×10-10, 95%CI: 2.88×10-10-3.69×10-10). The mutation rates of 0-, 1-, 2-, 3-, 5- and 7-14 years were 7.10×10-10, 6.06×10-10, 4.24×10-10, 5.34×10-10, 2.59×10-10 and 1.26×10-10 respectively. Conclusions: In the period of endogenous reactivation, the mutation rate of M. tuberculosis decreases with the interval time between initial treatment and relapse, which verifies the clinically observed phenomenon that the relapse often occurs within two years after the initial treatment of tuberculosis.
