title: Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.
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.
authors.affiliation: Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Merker
authors.affiliation: 1] Laboratoire Biologie Intégrative des Population, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, Paris, France. [2] Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Blin
authors.affiliation: 1] Laboratoire Biologie Intégrative des Population, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, Paris, France. [2] Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mona
authors.affiliation: Université Joseph Fourier, Centre National de la Recherche Scientifique, Laboratoire Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duforet-Frebourg
authors.affiliation: 1] INSERM U1019, Center for Infection and Immunity of Lille, Lille, France. [2] Centre National de la Recherche Scientifique, UMR 8204, Lille, France. [3] Université Lille Nord, Center for Infection and Immunity of Lille, Lille, France. [4] Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lecher
authors.affiliation: 1] INSERM U1019, Center for Infection and Immunity of Lille, Lille, France. [2] Centre National de la Recherche Scientifique, UMR 8204, Lille, France. [3] Université Lille Nord, Center for Infection and Immunity of Lille, Lille, France. [4] Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.affiliation: Université Joseph Fourier, Centre National de la Recherche Scientifique, Laboratoire Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, Grenoble, France.
authors.forename: Michael G B
authors.initials: MG
authors.lastname: Blum
authors.affiliation: National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rüsch-Gerdes
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, St. Petersburg, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Mokrousov
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Eman
authors.initials: E
authors.lastname: Aleksic
authors.affiliation: Genoscreen, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Allix-Béguec
authors.affiliation: Medical Department, Médecins sans Frontières Switzerland, Geneva, Switzerland.
authors.forename: Annick
authors.initials: A
authors.lastname: Antierens
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Ballif
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit-Tuberculosis, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barletta
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Beck
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.affiliation: Clinical Research Department, Epicentre, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Borroni
authors.affiliation: Department of Microbiology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Isolina
authors.initials: I
authors.lastname: Campos-Herrero
authors.affiliation: Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cirillo
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: Cox
authors.affiliation: 1] Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia. [2] Department of Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia. [3] Central Clinical School, Monash University, Melbourne, Victoria, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Crowe
authors.affiliation: National Tuberculosis Reference Laboratory, Phthysiopneumology Institute, Chisinau, Republic of Moldova.
authors.forename: Valeriu
authors.initials: V
authors.lastname: Crudu
authors.affiliation: Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Diel
authors.affiliation: 1] Public Health England National Mycobacterial Reference Laboratory and Clinical Tuberculosis and Human Immunodeficiency Virus Group, Queen Mary's School of Medicine and Dentistry, London, UK. [2] Department of Infectious Diseases, Imperial College, London, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
authors.affiliation: Tuberculosis and Mycobacteria, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Maryse
authors.initials: M
authors.lastname: Fauville-Dufaux
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Solomon
authors.initials: S
authors.lastname: Ghebremichael
authors.affiliation: Department of Science and Technology/National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research/Medical Research Council, Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Hanekom
authors.affiliation: Department of Diagnostics and Vaccinology, Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Jiao
authors.affiliation: US Agency for International Development Quality Health Care Project, Bishkek, Kyrgyzstan.
authors.forename: Stobdan
authors.initials: S
authors.lastname: Kalon
authors.affiliation: Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kohl
authors.affiliation: Samara Oblast Tuberculosis Service, Samara, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Kontsevaya
authors.affiliation: Statens Serum Institute, International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Lillebæk
authors.affiliation: Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Maeda
authors.affiliation: 1] Public Health England National Mycobacterial Reference Laboratory and Clinical Tuberculosis and Human Immunodeficiency Virus Group, Queen Mary's School of Medicine and Dentistry, London, UK. [2] Department of Infectious Diseases, Imperial College, London, UK.
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.affiliation: Statens Serum Institute, International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: World Health Organization Supranational Tuberculosis Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, France.
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.affiliation: Instituto de Investigación Sanitaria Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Samper
authors.affiliation: Clinical Research Department, Epicentre, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sanchez-Padilla
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Savic
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Isdore Chola
authors.initials: IC
authors.lastname: Shamputa
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Adong
authors.initials: A
authors.lastname: Shen
authors.affiliation: Central Tuberculosis Laboratory, Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Li-Hwei
authors.initials: LH
authors.lastname: Sng
authors.affiliation: Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
authors.forename: Petras
authors.initials: P
authors.lastname: Stakenas
authors.affiliation: Tartu University Hospital United Laboratories, Mycobacteriology, Tartu, Estonia.
authors.forename: Kadri
authors.initials: K
authors.lastname: Toit
authors.affiliation: Medical Department, Médecins sans Frontières, Paris, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Varaine
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Vukovic
authors.affiliation: Genoscreen, Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Wahl
authors.affiliation: Department of Science and Technology/National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research/Medical Research Council, Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Robin
authors.initials: R
authors.lastname: Warren
authors.affiliation: 1] INSERM U1019, Center for Infection and Immunity of Lille, Lille, France. [2] Centre National de la Recherche Scientifique, UMR 8204, Lille, France. [3] Université Lille Nord, Center for Infection and Immunity of Lille, Lille, France. [4] Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France. [5] Genoscreen, Lille, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
authors.affiliation: 1] Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany. [2] German Center for Infection Research, Borstel Site, Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.affiliation: 1] Laboratoire Biologie Intégrative des Population, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, Paris, France. [2] Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wirth
mesh_terms: D005075:Biological Evolution; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D005838:Genotype; D014943:Global Health; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D010802:Phylogeny; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*