edoc

The molecular clock of Mycobacterium tuberculosis

Menardo, Fabrizio and Duchêne, Sebastian and Brites, Daniela and Gagneux, Sebastien. (2019) The molecular clock of Mycobacterium tuberculosis. PLoS Pathogens, 15 (9). e1008067.

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Official URL: https://edoc.unibas.ch/71984/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Menardo, Fabrizio and Brites, Daniela and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1553-7366
e-ISSN:1553-7374
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Sep 2019 07:24
Deposited On:30 Sep 2019 07:24

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