Genomic differentiation within East Asian Helicobacter pylori
Genomic differentiation within East Asian Helicobacter pylori
ABSTRACT The East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidence and the population structure of Helicobacter pylori in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in H. pylori between these areas to identify sequence polymorphisms associated with increased cancer risk. We analysed 381 H. pylori genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of Single Nucleotide Polymorphisms (SNPs) with a highest fixation index (Fst) between subpopulations were examined by mapping amino-acid changes on 3D protein structure, solved or modelled. 329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven sub-regional clusters were found within hspEAsia, related to sub-populations with various ethnicities, geographies and gastric cancer risks. Sub-population-specific amino-acid changes were found in multi-drug exporters (hefC), transporters (frpB-4), outer membrane proteins (hopI), and several genes involved in host interaction, such as catalase, involved in H2O2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits including frpB-4, hefC, alpB/hopB, and hofC. were also differentiated within the Americas, indicating that a handful of genes may be key to local geographic adaptation. H. pylori within East Asia are not homogeneous but have become differentiated geographically at multiple loci that have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.
He Lihua、Cha Jeong-Heon、Falush Daniel、Yahara Koji、Zhang Jianzhong、Yamaoka Yoshio、Thorell Kaisa、Murakami Kazunari、TEAMHp、You Yuanhai、Kobayashi Ichizo、Katsura Yukako
State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionDepartment of Oral Biology, BK21 Plus Project, Yonsei University College of DentistryThe Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesAntimicrobial Resistance Research Center, National Institute of Infectious DiseasesState Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionDepartment of Environmental and Preventive Medicine, Oita University Faculty of MedicineDepartment of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg||Department of Clinical Microbiology, Sahlgrenska University Hospital, V?stra G?taland RegionDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityTEAMHp (Team for East Asian Genomics of Helicobacter pyloriState Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionI2BC, University of Paris-Saclay||Department of Infectious Diseases, Kyorin University School of Medicine||Department of Computational Biology and Medical Sciences (formerly Department of Medical Genome Sciences), Graduate School of Frontier Sciences, University of Tokyo||Institute of Medical Science, University of Tokyo||Research Center for Micro-Nano Technology, Hosei UniversityPrimate Research Institute, Kyoto University
肿瘤学基础医学微生物学
population genomicsFstmultidrug efflux pumpouter membrane proteinflagellin glycosylationbacterial pathogenesisgastric cancer
He Lihua,Cha Jeong-Heon,Falush Daniel,Yahara Koji,Zhang Jianzhong,Yamaoka Yoshio,Thorell Kaisa,Murakami Kazunari,TEAMHp,You Yuanhai,Kobayashi Ichizo,Katsura Yukako.Genomic differentiation within East Asian Helicobacter pylori[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.06.05.447026.点此复制
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