title: Genetic features of Mycobacterium tuberculosis modern Beijing sublineage.
abstract: Mycobacterium tuberculosis (MTB) Beijing strains have caused a great concern because of their rapid emergence and increasing prevalence in worldwide regions. Great efforts have been made to investigate the pathogenic characteristics of Beijing strains such as hypervirulence, drug resistance and favoring transmission. Phylogenetically, MTB Beijing family was divided into modern and ancient sublineages. Modern Beijing strains displayed enhanced virulence and higher prevalence when compared with ancient Beijing strains, but the genetic basis for this difference remains unclear. In this study, by analyzing previously published sequencing data of 1082 MTB Beijing isolates, we determined the genetic changes that were commonly present in modern Beijing strains but absent in ancient Beijing strains. These changes include 44 single-nucleotide polymorphisms (SNPs) and two short genomic deletions. Through bioinformatics analysis, we demonstrated that these genetic changes had high probability of functional effects. For example, 4 genes were frameshifted due to premature stop mutation or genomic deletions, 19 nonsynonymous SNPs located in conservative codons, and there is a significant enrichment in regulatory network for all nonsynonymous mutations. Besides, three SNPs located in promoter regions were verified to alter downstream gene expressions. Our study precisely defined the genetic features of modern Beijing strains and provided interesting clues for future researches to elucidate the mechanisms that underlie this sublineage's successful expansion. These findings from the analysis of the modern Beijing sublineage could provide us a model to understand the dynamics of pathogenicity of MTB.
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: 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: Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Dong
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: Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Zhu
authors.initials: Z
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: Mingyun
authors.initials: M
authors.lastname: Gan
authors.affiliation: Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention, Shanghai 200336, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention, Shanghai 200336, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
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: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000068476:Beijing; D019295:Computational Biology; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000472:pathogenicity; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion