title: Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis.
abstract: OBJECTIVE
  To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual.
  
  
  METHODS
  We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history.
  
  
  RESULTS
  The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years.
  
  
  CONCLUSIONS
  Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy.
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China Department of Immunology, Binzhou Medical University, Yantai, China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
authors.forename: Xavier
authors.initials: X
authors.lastname: Didelot
authors.affiliation: The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China.
authors.forename: Zhongbiao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Li
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: He
authors.affiliation: The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yuanhai
authors.initials: Y
authors.lastname: You
authors.affiliation: The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China.
authors.forename: Minqiao
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Minli
authors.initials: M
authors.lastname: Zhang
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Bo
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Daniel
authors.initials: D
authors.lastname: Falush
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Shengqi
authors.initials: S
authors.lastname: Wang
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, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D002908:Chronic Disease; D060085:Coinfection; D005756:Gastritis / Q000382:microbiology*; D023281:Genomics; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000145:classification* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: Helicobacter Pylori