title: Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese.
abstract: The Beijing family is the most successful genotype of Mycobacterium tuberculosis and responsible for more than a quarter of the global tuberculosis epidemic. As the predominant genotype in East Asia, the Beijing family has been emerging in various areas of the world and is often associated with disease outbreaks and antibiotic resistance. Revealing the origin and historical dissemination of this strain family is important for understanding its current global success. Here we characterized the global diversity of this family based on whole-genome sequences of 358 Beijing strains. We show that the Beijing strains endemic in East Asia are genetically diverse, whereas the globally emerging strains mostly belong to a more homogenous subtype known as "modern" Beijing. Phylogeographic and coalescent analyses indicate that the Beijing family most likely emerged around 30,000 y ago in southern East Asia, and accompanied the early colonization by modern humans in this area. By combining the genomic data and genotyping result of 1,793 strains from across China, we found the "modern" Beijing sublineage experienced massive expansions in northern China during the Neolithic era and subsequently spread to other regions following the migration of Han Chinese. Our results support a parallel evolution of the Beijing family and modern humans in East Asia. The dominance of the "modern" Beijing sublineage in East Asia and its recent global emergence are most likely driven by its hypervirulence, which might reflect adaption to increased human population densities linked to the agricultural transition in northern China.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Laboratory of Infection and Immunity, School of Basic Medical Science, West China Center of Medical Sciences, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Genomics and Health Unit, FISABIO Public Health, Valencia 46020, Spain; CIBER (Centros de Investigación Biomédica en Red) in Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid 28029, Spain;
authors.forename: Iñaki
authors.initials: I
authors.lastname: Comas
authors.affiliation: Department of Tuberculosis Control, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi 530028, China;
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing 100013, China;
authors.forename: Bing
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China;
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China;
authors.forename: Lanhai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
authors.forename: Chongguang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
authors.forename: Mingyu
authors.initials: M
authors.lastname: Gan
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China;
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Tuberculosis Control, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi 530028, China;
authors.forename: Feiying
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel 4002, University of Basel, Basel CH-4003, Switzerland; qiangao@shmu.edu.cn sebastien.gagneux@unibas.ch meijiansh@aliyun.com gxlrshu@163.com wankanglin@icdc.cn.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; qiangao@shmu.edu.cn sebastien.gagneux@unibas.ch meijiansh@aliyun.com gxlrshu@163.com wankanglin@icdc.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Tuberculosis Control, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi 530028, China; qiangao@shmu.edu.cn sebastien.gagneux@unibas.ch meijiansh@aliyun.com gxlrshu@163.com wankanglin@icdc.cn.
authors.forename: Rushu
authors.initials: R
authors.lastname: Lan
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China qiangao@shmu.edu.cn sebastien.gagneux@unibas.ch meijiansh@aliyun.com gxlrshu@163.com wankanglin@icdc.cn.
authors.forename: Kanglin
authors.initials: K
authors.lastname: Wan
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; qiangao@shmu.edu.cn sebastien.gagneux@unibas.ch meijiansh@aliyun.com gxlrshu@163.com wankanglin@icdc.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D002681:China; D005006:Ethnicity; D005798:Genes, Bacterial; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D014376:Tuberculosis / Q000208:ethnology / Q000382:microbiology*
keywords: Han Chinese; MTBC Beijing family; expansion; origin