Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage

This article has been updated

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Biogeographical structure of the M. tuberculosis Beijing lineage.
Figure 2: Phylogenetic reconstruction of the MTBC Beijing lineage and change in population size through time.
Figure 3: Proportions of MDR tuberculosis strains among the six CCs and BL of the Beijing lineage.
Figure 4: SNP-based Bayesian factor model analysis for detecting genes involved in positive selection in the Beijing lineage.

Accession codes

Primary accessions

European Nucleotide Archive

Referenced accessions

NCBI Reference Sequence

Change history

  • 10 February 2015

    In the version of this article initially published online, affiliation 3 was incomplete, and the middle initials of author Michael Blum were inadvertently omitted. These errors have been corrected for the print, PDF and HTML versions of this article.

References

  1. 1

    Global Tuberculosis Report. (World Health Organization, Geneva, 2013).

  2. 2

    Klopper, M. et al. Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerg. Infect. Dis. 19, 449–455 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Casali, N. et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat. Genet. 46, 279–286 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Stoffels, K. et al. From multidrug- to extensively drug-resistant tuberculosis: upward trends as seen from a 15-year nationwide study. PLoS ONE 8, e63128 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Niemann, S. et al. Mycobacterium tuberculosis Beijing lineage favors the spread of multidrug-resistant tuberculosis in the Republic of Georgia. J. Clin. Microbiol. 48, 3544–3550 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Mokrousov, I. Insights into the origin, emergence, and current spread of a successful Russian clone of Mycobacterium tuberculosis. Clin. Microbiol. Rev. 26, 342–360 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Munsiff, S.S. et al. Persistence of a highly resistant strain of tuberculosis in New York City during 1990–1999. J. Infect. Dis. 188, 356–363 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    Cowley, D. et al. Recent and rapid emergence of W-Beijing strains of Mycobacterium tuberculosis in Cape Town, South Africa. Clin. Infect. Dis. 47, 1252–1259 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Caminero, J.A. et al. Epidemiological evidence of the spread of a Mycobacterium tuberculosis strain of the Beijing genotype on Gran Canaria Island. Am. J. Respir. Crit. Care Med. 164, 1165–1170 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Ford, C.B. et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat. Genet. 45, 784–790 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Comas, I. & Gagneux, S. A role for systems epidemiology in tuberculosis research. Trends Microbiol. 19, 492–500 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Casali, N. et al. Microevolution of extensively drug-resistant tuberculosis in Russia. Genome Res. 22, 735–745 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Glynn, J.R., Whiteley, J., Bifani, P.J., Kremer, K. & van Soolingen, D. Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis: a systematic review. Emerg. Infect. Dis. 8, 843–849 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Bifani, P.J., Mathema, B., Kurepina, N.E. & Kreiswirth, B.N. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol. 10, 45–52 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Parwati, I., van Crevel, R. & van Soolingen, D. Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains. Lancet Infect. Dis. 10, 103–111 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    Hanekom, M. et al. Mycobacterium tuberculosis Beijing genotype: a template for success. Tuberculosis (Edinb.) 91, 510–523 (2011).

    Article  CAS  Google Scholar 

  17. 17

    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 

  18. 18

    Kato-Maeda, M. et al. Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig. Clin. Vaccine Immunol. 19, 1227–1237 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Weniger, T., Krawczyk, J., Supply, P., Niemann, S. & Harmsen, D. MIRU-VNTRplus: a web tool for polyphasic genotyping of Mycobacterium tuberculosis complex bacteria. Nucleic Acids Res. 38, W326–W331 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Plikaytis, B.B. et al. Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis. J. Clin. Microbiol. 32, 1542–1546 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Kalinowski, S.T. Counting alleles with rarefaction: private alleles and hierarchicalsampling design. Conserv. Genet. 5, 539–543 (2004).

    Article  CAS  Google Scholar 

  22. 22

    Supply, P., Niemann, S. & Wirth, T. On the mutation rates of spoligotypes and variable numbers of tandem repeat loci of Mycobacterium tuberculosis. Infect. Genet. Evol. 11, 251–252 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Reyes, J.F. & Tanaka, M.M. Mutation rates of spoligotypes and variable numbers of tandem repeat loci in Mycobacterium tuberculosis. Infect. Genet. Evol. 10, 1046–1051 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Ragheb, M.N. et al. The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection. BMC Genomics 14, 145 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    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 

  26. 26

    Walker, T.M. et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect. Dis. 13, 137–146 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Nieselt-Struwe, K. & von Haeseler, A. Quartet-mapping, a generalization of the likelihood-mapping procedure. Mol. Biol. Evol. 18, 1204–1219 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Namouchi, A., Didelot, X., Schock, U., Gicquel, B. & Rocha, E.P. After the bottleneck: genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection. Genome Res. 22, 721–734 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Roetzer, A. et al. Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study. PLoS Med. 10, e1001387 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Ford, C.B. et al. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat. Genet. 43, 482–486 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Comas, I. & Gagneux, S. The past and future of tuberculosis research. PLoS Pathog. 5, e1000600 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Colditz, G.A. et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. J. Am. Med. Assoc. 271, 698–702 (1994).

    Article  CAS  Google Scholar 

  33. 33

    Holden, C. Stalking a killer in Russia's prisons. Science 286, 1670 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Bifani, P.J. et al. Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. J. Am. Med. Assoc. 275, 452–457 (1996).

    Article  CAS  Google Scholar 

  35. 35

    Parish, T. et al. Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis. Infect. Immun. 71, 1134–1140 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Duforet-Frebourg, N., Bazin, E. & Blum, M.G. Genome scans for detecting footprints of local adaptation using a Bayesian factor model. Mol. Biol. Evol. 31, 2483–2495 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Maloney, E. et al. The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides. PLoS Pathog. 5, e1000534 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Sirakova, T.D., Fitzmaurice, A.M. & Kolattukudy, P. Regulation of expression of mas and fadD28, two genes involved in production of dimycocerosyl phthiocerol, a virulence factor of Mycobacterium tuberculosis. J. Bacteriol. 184, 6796–6802 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Ebrahimi-Rad, M. et al. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg. Infect. Dis. 9, 838–845 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Etienne, G. et al. Identification of the polyketide synthase involved in the biosynthesis of the surface-exposed lipooligosaccharides in mycobacteria. J. Bacteriol. 191, 2613–2621 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Ahmad, S., El-Shazly, S., Mustafa, A.S. & Al-Attiyah, R. Mammalian cell-entry proteins encoded by the mce3 operon of Mycobacterium tuberculosis are expressed during natural infection in humans. Scand. J. Immunol. 60, 382–391 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Li, X.Z., Zhang, L. & Nikaido, H. Efflux pump–mediated intrinsic drug resistance in Mycobacterium smegmatis. Antimicrob. Agents Chemother. 48, 2415–2423 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Meikle, V. et al. Identification of novel Mycobacterium bovis antigens by dissection of crude protein fractions. Clin. Vaccine Immunol. 16, 1352–1359 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    de Vos, M. et al. Putative compensatory mutations in the rpoC gene of rifampin-resistant Mycobacterium tuberculosis are associated with ongoing transmission. Antimicrob. Agents Chemother. 57, 827–832 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Comas, I. et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat. Genet. 44, 106–110 (2012).

    Article  CAS  Google Scholar 

  46. 46

    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 

  47. 47

    Fuller, D.Q. et al. The domestication process and domestication rate in rice: spikelet bases from the Lower Yangtze. Science 323, 1607–1610 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Fang, J. Atlas for Sustainability in Polynesian Island Cultures and Ecosystems (Sea Education Association, 2013).

  49. 49

    Laruelle, M. & Peyrouse, S. Cross-border minorities as cultural and economic mediators between China and Central Asia. China and Eurasia Forum Quarterly 7, 93–119 (2009).

    Google Scholar 

  50. 50

    Drolet, G.J. World War I and tuberculosis. A statistical summary and review. Am. J. Public Health Nations Health 35, 689–697 (1945).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Bryant, J.M. et al. Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data. BMC Infect. Dis. 13, 110 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    Aguilar, D. et al. Mycobacterium tuberculosis strains with the Beijing genotype demonstrate variability in virulence associated with transmission. Tuberculosis (Edinb.) 90, 319–325 (2010).

    Article  CAS  Google Scholar 

  53. 53

    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 

  54. 54

    Gioffré, A. et al. Mutation in mce operons attenuates Mycobacterium tuberculosis virulence. Microbes Infect. 7, 325–334 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Stavrum, R. et al. Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex. PLoS ONE 6, e26295 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Ahidjo, B.A. et al. VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins. PLoS ONE 6, e21738 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Osório, N.S. et al. Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure. Mol. Biol. Evol. 30, 1326–1336 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    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  PubMed Central  Google Scholar 

  59. 59

    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 

  60. 60

    Supply, P. et al. Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. J. Clin. Microbiol. 39, 3563–3571 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Supply, P. et al. Proposal for standardization of optimized mycobacterial interspersed repetitive unit–variable number tandem repeat typing of Mycobacterium tuberculosis. J. Clin. Microbiol. 44, 4498–4510 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Kalinowski, S.T. HP-rare: a computer program for performing rarefaction on measures of allelic diversity. Mol. Ecol. Notes 5, 187–189 (2005).

    Article  CAS  Google Scholar 

  63. 63

    Beaumont, M.A. Detecting population expansion and decline using microsatellites. Genetics 153, 2013–2029 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Wilson, I.J., Weale, M.E. & Balding, D.J. Inferences from DNA data: population histories, evolutionary processes and forensic match probabilities. J. R. Stat. Soc. Ser. A Stat. Soc. 166, 155–188 (2003).

    Article  Google Scholar 

  65. 65

    Wilson, I.J. & Balding, D.J. Genealogical inference from microsatellite data. Genetics 150, 499–510 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Ohta, T. & Kimura, M. A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population. Genet. Res. 22, 201–204 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Metropolis, N., Rosenbluth, A.W., Rosenbluth, M.N., Teller, A.H. & Teller, E. Equations of state calculations by fast computing machine. J. Chem. Phys. 21, 1087–1091 (1953).

    Article  CAS  Google Scholar 

  68. 68

    Hastings, W.K. Monte Carlo sampling methods using Markov chains and their applications. Biometrika 57, 97–109 (1970).

    Article  Google Scholar 

  69. 69

    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 

  70. 70

    Blom, J. et al. Exact and complete short-read alignment to microbial genomes using Graphics Processing Unit programming. Bioinformatics 27, 1351–1358 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Schmidt, H.A., Strimmer, K., Vingron, M. & von Haeseler, A. TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 18, 502–504 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Guindon, S. & Gascuel, O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52, 696–704 (2003).

    Article  Google Scholar 

  73. 73

    Posada, D. & Crandall, K.A. MODELTEST: testing the model of DNA substitution. Bioinformatics 14, 817–818 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Hasegawa, M., Kishino, H. & Yano, T. Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J. Mol. Evol. 22, 160–174 (1985).

    Article  CAS  Google Scholar 

  75. 75

    Drummond, A.J., Rambaut, A., Shapiro, B. & Pybus, O.G. Bayesian coalescent inference of past population dynamics from molecular sequences. Mol. Biol. Evol. 22, 1185–1192 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Drummond, A.J. & Rambaut, A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol. Biol. 7, 214 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Casali, N. & Riley, L.W. A phylogenomic analysis of the Actinomycetales mce operons. BMC Genomics 8, 60 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Zhang, Z. et al. KaKs_Calculator: calculating Ka and Ks through model selection and model averaging. Genomics Proteomics Bioinformatics 4, 259–263 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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.

Author information

Affiliations

Authors

Contributions

I.M., P. Supply, S.N. and T.W. designed the study. M.M., P. Supply, S.N. and T.W. analyzed data and wrote the manuscript with comments from all authors. M.M., C.B., S. Mona and T.W. performed population genetics and phylogenetic analyses. M.M., N.D.-F., M.G.B.B. and T.W. conducted selection tests. T.A.K. performed whole-genome sequencing and SNP calling. P. Supply, M.M., E.W., S.L., S.R.-G., I.M., S.N., E.A., C.A.-B., A.A., E.A.-K., M. Ballif, F.B., H.P.B., C.E.B., M. Bonnet, E.B., I.C.-H., D.C., H.C., S.C., V.C., R.D., F.D., M.F.-D., S. Gagneux, S. Ghebremichael, M.H., S.H., W.-w.J., S.K., I.K., T.L., S. Maeda, V.N., M.R., N.R., S.S., E.S.-P., B.S., I.C.S., A.S., L.-H.S., P. Stakenas, K.T., F.V., D.V., C.W. and R.W. obtained mycobacterial genotyping data and drug susceptibility test results.

Corresponding authors

Correspondence to Philip Supply or Stefan Niemann or Thierry Wirth.

Ethics declarations

Competing interests

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 information

Supplementary Text and Figures

Supplementary Figures 1–10 and Supplementary Tables 2–10 and 12. (PDF 15198 kb)

Supplementary Table 1

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)

Supplementary Table 11

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)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing