Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.
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We gratefully acknowledge L. Cowan and J. Posey (US Centers for Disease Control and Prevention) for providing us with significant amounts of genotyping data for M. tuberculosis Beijing isolates. We thank T. Ubben, I. Radzio, T. Struwe-Sonnenschein and J. Zallet (Research Center Borstel) for excellent technical assistance. We acknowledge J. Peh for her assistance and support in the study and I. Comas for statistical advice. Parts of this work have been supported by grants from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 278864 in the framework of the European Union PathoNGenTrace project and grant agreement 223681 in the framework of the TB-PAN-NET project. We also thank Action Transversale du Muséum National d'Histoire Naturelle 'Les Microorganismes, Acteurs Clés dans les Ecosystèmes' for financial support. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
P. Supply is a consultant for Genoscreen. C.A.-B. and C.W. were or are employees of the same company. The other authors declare no competing financial interests.
Supplementary Figures 1–10 and Supplementary Tables 2–10 and 12. (PDF 15198 kb)
Genotyping results (24-locus MIRU-VNTR), country of origin, geolocalization and available phenotypic drug susceptibility test results for 4,987 analyzed clinical isolates from the MTBC Beijing lineage. (XLSX 897 kb)
Top Bayes factor variants. SNPs are given relative to the H37Rv reference sequence, and putative targets of selection are highlighted. The color codes along the logBF column correspond, respectively, to SNPs specific to the central Asia outbreak (blue), the European-Russian W148 outbreak (green) and the members of the modern Beijing lineage (orange). (XLSX 2913 kb)
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Merker, M., Blin, C., Mona, S. et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet 47, 242–249 (2015). https://doi.org/10.1038/ng.3195
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