A small number of high-burden countries account for the majority of tuberculosis cases worldwide. Detailed data are lacking from these regions. To explore the evolutionary history of Mycobacterium tuberculosis in China—the country with the third highest tuberculosis burden—we analysed a countrywide collection of 4,578 isolates. Little genetic diversity was detected, with 99.4% of the bacterial population belonging to lineage 2 and three sublineages of lineage 4. The deeply rooted phylogenetic positions and geographic restriction of these four genotypes indicate that their populations expanded in situ following a small number of introductions to China. Coalescent analyses suggest that these bacterial subpopulations emerged in China around 1,000 years ago, and expanded in parallel from the twelfth century onwards, and that the whole population peaked in the late eighteenth century. More recently, sublineage L2.3, which is indigenous to China and exhibited relatively high transmissibility and extensive global dissemination, came to dominate the population dynamics of M. tuberculosis in China. Our results indicate that historical expansion of four M. tuberculosis strains shaped the current tuberculosis epidemic in China, and highlight the long-term genetic continuity of the indigenous M. tuberculosis population.
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Sequencing reads have been submitted to the European Nucleotide Archive (EMBL-EBI) under study accession PRJEB23157. The geographic information for individual isolates is listed in Supplementary Table 3. The analysis scripts used in this study are available online at GitHub (https://github.com/StopTB/China_TB_Evolutionary_History).
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We thank T. M. Walker for sharing the geographic information of 3,651 MTBC isolates of multiple continents origin. We also thank Y.-X. Fu and X. Liu for advice on effective population size calculation and fruitful discussions, and D. Brites and C. Wang for help with clarifying technical details of data analysis during this work. This work was supported by the Natural Science Foundation of China (91631301 and 81661128043 to Q.G. and 81701975 to Q.L.). C.S.P. was supported by the National Institutes of Health (grant 1R01AI113287-01A1). S.G. was supported by the Swiss National Science Foundation (grants IZRJZ3_164171, 310030_166687, IZLSZ3_170834 and CRSII5_177163). This work was also supported by MINECO research grant SAF2016-77346-R (to I.C.), the European Research Council (638553-TB-ACCELERATE to I.C.), the National Science and Technology Major Project of China (2017ZX10201302 to Q.G., 2018ZX10103001 to Y.Z.), the Sanming Project of Medicine in Shenzhen (SZSM201611030 to Q.G.), JSGG20170413142559220 (to Q.G.), and National Basic Research programme of China (2014CB744403 to Y.Z.).
The authors declare no competing interests.
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Liu, Q., Ma, A., Wei, L. et al. China’s tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis. Nat Ecol Evol 2, 1982–1992 (2018). https://doi.org/10.1038/s41559-018-0680-6
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