China’s tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis

Abstract

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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Fig. 1: Genotyping results of countrywide collected MTBC strains in China.
Fig. 2: Low genetic diversity in China’s MTBC population.
Fig. 3: Single origins of the four indigenous genotypes.
Fig. 4: Historical expansions of indigenous MTBC genotypes.
Fig. 5: Global dispersal of Chinese indigenous genotypes.
Fig. 6: Contour maps showing the countrywide prevalence of indigenous sublineages.

Data availability

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).

References

  1. 1.

    Bos, K. I. et al. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514, 494–497 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Global Tuberculosis Report 2017 (World Health Organization, 2017).

  3. 3.

    Narain, J. P., Raviglione, M. C. & Kochi, A. HIV-associated tuberculosis in developing countries: epidemiology and strategies for prevention. Tuber. Lung Dis. 73, 311–321 (1992).

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Steffen, R., Rickenbach, M., Wilhelm, U., Helminger, A. & Schar, M. Health problems after travel to developing countries. J. Infect. Dis. 156, 84–91 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Fusegawa, H. et al. Outbreak of tuberculosis in a 2000-year-old Chinese population. Kansenshogaku Zasshi 77, 146–149 (2003).

    Article  PubMed  Google Scholar 

  6. 6.

    Prasad, P. V. General medicine in Atharvaveda with special reference to Yaksma (consumption/tuberculosis). Bull. Indian Inst. Hist. Med. Hyderabad 32, 1–14 (2002).

    CAS  PubMed  Google Scholar 

  7. 7.

    Suzuki, T. & Inoue, T. Earliest evidence of spinal tuberculosis from the Aneolithic Yayoi period in Japan. Int. J. Osteoarchaeol. 17, 392–402 (2007).

    Article  Google Scholar 

  8. 8.

    Li, X. et al. Archaeological and palaeopathological study on the third/second century bc grave from Turfan, China: individual health history and regional implications. Quat. Int. 290, 335–343 (2013).

    Article  Google Scholar 

  9. 9.

    Packard, R. M. White Plague, Black Labor: Tuberculosis and the Political Economy of Health and Disease in South Africa (Univ. California Press, Berkeley, 1989).

  10. 10.

    Dubos, R. J. & Dubos, J. The White Plague: Tuberculosis, Man, and Society (Rutgers Univ. Press, New Brunswick, 1952).

  11. 11.

    Stead, W. W. The origin and erratic global spread of tuberculosis. How the past explains the present and is the key to the future. Clin. Chest Med. 18, 65–77 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Zhang, Z. Epidemic Chronology of Ancient China [in Chinese] (Fujian Science and Technology Press, Fuzhou, 2007).

  13. 13.

    Bates, J. H. & Stead, W. W. The history of tuberculosis as a global epidemic. Med. Clin. North Am. 77, 1205–1217 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Perry, E. J. & Selden, M. Chinese Society: Change, Conflict and Resistance (Routledge, London, 2003).

  15. 15.

    Wang, F. & Zuo, X. Inside China’s cities: institutional barriers and opportunities for urban migrants. Am. Econ. Rev. 89, 276–280 (1999).

    Article  Google Scholar 

  16. 16.

    O’Neill, M. B. et al. Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia. Preprint at https://www.biorxiv.org/content/early/2017/10/27/210161 (2017).

  17. 17.

    Pepperell, C. S. et al. Dispersal of Mycobacterium tuberculosis via the Canadian fur trade. Proc. Natl Acad. Sci. USA 108, 6526–6531 (2011).

    Article  PubMed  Google Scholar 

  18. 18.

    Hershberg, R. et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol. 6, e311 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Wirth, T. et al. Origin, spread and demography of the Mycobacterium tuberculosis complex. PLoS. Pathog. 4, e1000160 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Gagneux, S. & Small, P. M. Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect. Dis. 7, 328–337 (2007).

    Article  PubMed  Google Scholar 

  21. 21.

    Stucki, D. et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat. Genet. 48, 1535–1543 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Linz, B. et al. An African origin for the intimate association between humans and Helicobacter pylori. Nature 445, 915–918 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Pepperell, C. S. et al. The role of selection in shaping diversity of natural M. tuberculosis populations. PLoS Pathog. 9, e1003543 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Bjorn-Mortensen, K. et al. Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland. Sci. Rep. 6, 33180 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Lee, R. S. et al. Population genomics of Mycobacterium tuberculosis in the Inuit. Proc. Natl Acad. Sci. USA 112, 13609–13614 (2015).

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Comas, I. et al. Population genomics of Mycobacterium tuberculosis in Ethiopia contradicts the virgin soil hypothesis for human tuberculosis in Sub-Saharan Africa. Curr. Biol. 25, 3260–3266 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Holt, K. E. et al. Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam. Nat. Genet. 50, 849–856 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Van Soolingen, D. et al. Predominance of a single genotype of Mycobacterium tuberculosis in countries of east Asia. J. Clin. Microbiol. 33, 3234–3238 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Pang, Y. et al. Spoligotyping and drug resistance analysis of Mycobacterium tuberculosis strains from national survey in China. PLoS ONE 7, e32976 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Coll, F. et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat. Commun. 5, 4812 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Comas, I. et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat. Genet. 45, 1176–1182 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Ge, J. China Population History (Zhongguo Renkou Shi) (Fudan Univ. Press, Shanghai, 2000).

  33. 33.

    Wang, L. et al. Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data. Lancet 383, 2057–2064 (2014).

    Article  PubMed  Google Scholar 

  34. 34.

    Neher, R. A. & Hallatschek, O. Genealogies of rapidly adapting populations. Proc. Natl Acad. Sci. USA 110, 437–442 (2013).

    Article  PubMed  Google Scholar 

  35. 35.

    Magiorkinis, G. et al. Integrating phylodynamics and epidemiology to estimate transmission diversity in viral epidemics. PLoS Comput. Biol. 9, e1002876 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Guang-Hui, H. Historical Population Geography of Beijing [in Chinese] (Peking Univ. Press, Beijing, 1996).

  37. 37.

    Hou Ren-Zhi, T. X.-F. Historical Geography of Beijing City [in Chinese] (Beijing Yanshan Press, Beijing, 2000).

  38. 38.

    Huang, Q.-S. & Yang, G.-H. The placename of immigration in Sichuan and Huguang people migrate into Sichuan. J. Southwest China Normal Univ. 3, 023 (2005).

    Google Scholar 

  39. 39.

    Millward, J. A. Eurasian Crossroads: A History of Xinjiang (Columbia Univ. Press, New York, 2007).

  40. 40.

    Poston, D. L. Jr., Mao, M. X. & Yu, M.-Y. The global distribution of the overseas Chinese around 1990. Popul. Dev. Rev. 20, 631–645 (1994).

    Article  Google Scholar 

  41. 41.

    Li, P. S. The rise and fall of Chinese immigration to Canada: newcomers from Hong Kong special administrative region of China and mainland China, 1980–2000. Int. Migr. 43, 9–34 (2005).

    Article  Google Scholar 

  42. 42.

    King, H. & Locke, F. B. Chinese in the United States: a century of occupational transition. Int. Migr. Rev. 14, 15–42 (1980).

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Gagneux, S. et al. Variable host–pathogen compatibility in Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 103, 2869–2873 (2006).

    Article  CAS  PubMed  Google Scholar 

  44. 44.

    McNeill, W. H. Human migration in historical perspective. Popul. Dev. Rev. 10, 1–18 (1984).

    Article  Google Scholar 

  45. 45.

    Gan, F. Ancient Glass Research Along the Silk Road (World Scientific, Hackensack, 2009).

  46. 46.

    Kauz, R. Aspects of the Maritime Silk Road: From the Persian Gulf to the East China Sea (Harrassowitz, Wiesbaden, 2010).

  47. 47.

    McPherson, K. China and the Maritime Silk Route. In Proc. of the UNESCO Quanzhou International Seminar on China and the Maritime Routes of the Silk Roads 55–60 (People’s Publishing House, 1991).

  48. 48.

    Lin, J. Y. The Needham puzzle: why the industrial revolution did not originate in China. Econ. Dev. Cult. Change 43, 269–292 (1995).

    Article  Google Scholar 

  49. 49.

    Jones, E. L., Frost, L. & White, C. Coming Full Circle: An Economic History of the Pacific Rim (Westview Press, Colorado, 1993).

  50. 50.

    Yusuf, S. & Saich, A. China Urbanizes: Consequences, Strategies, and Policies (World Bank, Washington DC, 2008).

  51. 51.

    Millward, J., Dunnell, R. W., Elliott, M. C. & Forêt, P. New Qing Imperial History. Making of Inner Asian Empire at Qing Chengde (RoutledgeCurzon, New York, 2004).

  52. 52.

    Mote, F. W., Twitchett, D. & Fairbank, J. K. The Cambridge History of China: Volume 7, The Ming Dynasty, 1368–1644 (Cambridge Univ. Press, London, 1988).

  53. 53.

    Yang, C. et al. Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study. Clin. Infect. Dis. 61, 219–227 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Ackley, S. F., Liu, F., Porco, T. C. & Pepperell, C. S. Modeling historical tuberculosis epidemics among Canadian First Nations: effects of malnutrition and genetic variation. PeerJ 3, e1237 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Yang, C. et al. Mycobacterium tuberculosis Beijing strains favor transmission but not drug resistance in China. Clin. Infect. Dis. 55, 1179–1187 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    De Jong, B. C. et al. Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia. J. Infect. Dis. 198, 1037–1043 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Liu, Q. et al. Genetic features of Mycobacterium tuberculosis modern Beijing sublineage. Emerg. Microbes Infect. 5, e14 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Van Laarhoven, A. et al. Low induction of proinflammatory cytokines parallels evolutionary success of modern strains within the Mycobacterium tuberculosis Beijing genotype. Infect. Immun. 81, 3750–3756 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Ribeiro, S. C. et al. Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage. J. Clin. Microbiol. 52, 2615–2624 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Ates, L. S. et al. Mutations in ppe38 block PE_PGRS secretion and increase virulence of Mycobacterium tuberculosis. Nat. Microbiol. 3, 181–188 (2018).

    Article  CAS  PubMed  Google Scholar 

  61. 61.

    Kay, G. L. et al. Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe. Nat. Commun. 6, 6717 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Wirth, T. Massive lineage replacements and cryptic outbreaks of Salmonella Typhi in eastern and southern Africa. Nat. Genet. 47, 565–567 (2015).

    Article  CAS  PubMed  Google Scholar 

  63. 63.

    Wagner, D. M. et al. Yersinia pestis and the plague of Justinian 541–543 ad: a genomic analysis. Lancet Infect. Dis. 14, 319–326 (2014).

    Article  PubMed  Google Scholar 

  64. 64.

    Mutreja, A. et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 477, 462–465 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Vagene, A. J. et al. Salmonella enterica genomes from victims of a major sixteenth-century epidemic in Mexico. Nat. Ecol. Evol. 2, 520–528 (2018).

    Article  PubMed  Google Scholar 

  66. 66.

    Zhao, Y. et al. National survey of drug-resistant tuberculosis in China. N. Engl. J. Med. 366, 2161–2170 (2012).

    Article  CAS  PubMed  Google Scholar 

  67. 67.

    Liu, Q., Luo, T., Li, J., Mei, J. & Gao, Q. Triplex real-time PCR melting curve analysis for detecting Mycobacterium tuberculosis mutations associated with resistance to second-line drugs in a single reaction. J. Antimicrob. Chemother. 68, 1097–1103 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Farhat, M. R. et al. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat. Genet. 45, 1183–1189 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Comas, I., Homolka, S., Niemann, S. & Gagneux, S. Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PLoS ONE 4, e7815 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Luo, T. et al. Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc. Natl Acad. Sci. USA 112, 8136–8141 (2015).

    Article  CAS  PubMed  Google Scholar 

  71. 71.

    Merker, M. et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat. Genet. 47, 242–249 (2015).

    Article  CAS  PubMed  Google Scholar 

  72. 72.

    Barbier, M. & Wirth, T. The evolutionary history, demography, and spread of the Mycobacterium tuberculosis complex. Microbiol. Spectr. 4, TBTB2-0008-2016 (2016).

    Google Scholar 

  73. 73.

    Brudey, K. et al. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol. 6, 23 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Viegas, S. O. et al. Molecular diversity of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mozambique. BMC Microbiol. 10, 195 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Zhang, H. et al. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat. Genet. 45, 1255–1260 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. 76.

    Joshi, N. A. & Fass, J. N. Sickle: A Sliding-Window, Adaptive, Quality-Based Trimming Tool for FastQ Files (2011); https://github.com/najoshi/sickle

  77. 77.

    Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Gan, M., Liu, Q., Yang, C., Gao, Q. & Luo, T. Deep whole-genome sequencing to detect mixed infection of Mycobacterium tuberculosis. PLoS ONE 11, e0159029 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Tamura, K., Stecher, G., Peterson, D., Filipski, A. & Kumar, S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol. Biol. Evol. 30, 2725–2729 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Letunic, I. & Bork, P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 44, W242–W245 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    RStudio Team RStudio: Integrated Development for R (RStudio, 2015).

  84. 84.

    Paradis, E. pegas: an R package for population genetics with an integrated-modular approach. Bioinformatics 26, 419–420 (2010).

    Article  CAS  Google Scholar 

  85. 85.

    Hsieh, T., Ma, K. & Chao, A. iNEXT: an R package for rarefaction and extrapolation of species diversity (Hill numbers). Methods Ecol. Evol. 7, 1451–1456 (2016).

    Article  Google Scholar 

  86. 86.

    Yu, Y., Harris, A. J., Blair, C. & He, X. RASP (Reconstruct Ancestral State in Phylogenies): a tool for historical biogeography. Mol. Phylogenet. Evol. 87, 46–49 (2015).

    Article  PubMed  Google Scholar 

  87. 87.

    Drummond, A. J., Suchard, M. A., Xie, D. & Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969–1973 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Gignoux, C. R., Henn, B. M. & Mountain, J. L. Rapid, global demographic expansions after the origins of agriculture. Proc. Natl Acad. Sci. USA 108, 6044–6049 (2011).

    Article  PubMed  Google Scholar 

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Acknowledgements

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.).

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Q.L., Y.Z., C.S.P. and Q.G. designed and implemented the study. Y.P., B.W., Y.Z. and Q.G. collected and contributed the MTBC isolates analysed in this study. Q.L., A.M. and Y.Z. conducted the SNP genotyping work. M.L. and C.Y. conducted the MIRU-VNTR typing and analysis. Q.L., T.L., M.G. and T.Z. analysed the sequencing reads and performed the genetic analysis. L.W., H.-X.Z. and L.J. participated in the analysis of integrating tuberculosis history with Chinese human population history. Q.J. performed the statistical analysis. Q.L., I.C., S.G., C.S.P. and Q.G. drafted the manuscript. All authors critically reviewed and approved the final version of the manuscript.

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Correspondence to Yanlin Zhao or Caitlin S. Pepperell or Qian Gao.

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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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