The molecular clock of Mycobacterium tuberculosis


Autoři: Fabrizio Menardo aff001;  Sebastian Duchêne aff003;  Daniela Brites aff001;  Sebastien Gagneux aff001
Působiště autorů: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland aff001;  University of Basel, Basel, Switzerland aff002;  Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia aff003
Vyšlo v časopise: The molecular clock of Mycobacterium tuberculosis. PLoS Pathog 15(9): e1008067. doi:10.1371/journal.ppat.1008067
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008067

Souhrn

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.

Klíčová slova:

Biology and life sciences – Organisms – Bacteria – Actinobacteria – Mycobacterium tuberculosis – Evolutionary biology – Evolutionary systematics – Phylogenetics – Phylogenetic analysis – Evolutionary processes – Evolutionary rate – Molecular evolution – Taxonomy – Population biology – Population metrics – Population size – Population growth – Computer and information sciences – Data management – Medicine and health sciences – Infectious diseases – Bacterial diseases – Tuberculosis – Extensively drug-resistant tuberculosis – Tropical diseases


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