title: Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection.
abstract: Helicobacter pylori, a bacterial pathogen that can infect human stomach causing gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome diversity as the result of mutation and recombination. The bacteria often infect in childhood and persist for the life of the host. One of the reasons of the rapid evolution of H. pylori is that it changes its genome drastically for adaptation to a new host. To investigate microevolution and adaptation of the H. pylori genome, we undertook whole genome sequencing of the same or very similar sequence type in multi-locus sequence typing (MLST) with seven genes in members of the same family consisting of parents and children in Japan. Detection of nucleotide substitutions revealed likely transmission pathways involving children. Nonsynonymous (amino acid changing) mutations were found in virulence-related genes (cag genes, vacA, hcpDX, tnfα, ggt, htrA and the collagenase gene), outer membrane protein (OMP) genes and other cell surface-related protein genes, signal transduction genes and restriction-modification genes. We reconstructed various pathways by which H. pylori can adapt to a new human host, and our results raised the possibility that the mutational changes in virulence-related genes have a role in adaptation to a child host. Changes in restriction-modification genes might remodel the methylome and transcriptome to help adaptation. This study has provided insights into H. pylori transmission and virulence and has implications for basic research as well as clinical practice.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Minato-ku, Tokyo, Japan; Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo-shi, Hokkaido, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yonezawa
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Ishige
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Imai
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Shiwa
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Shibata-Hatta
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kanesaki
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan; Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Minato-ku, Tokyo, Japan; Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002648:Child; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial / Q000235:genetics*; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D058885:Multilocus Sequence Typing / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics; D014774:Virulence / Q000235:genetics*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial