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Open Access Highly Accessed Research article

Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes

Mikihiko Kawai123, Yoshikazu Furuta12, Koji Yahara45, Takeshi Tsuru26, Kenshiro Oshima7, Naofumi Handa12, Noriko Takahashi12, Masaru Yoshida8, Takeshi Azuma8, Masahira Hattori7*, Ikuo Uchiyama3 and Ichizo Kobayashi126*

Author Affiliations

1 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan

2 Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan

3 National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi, 444-8585, Japan

4 Graduate School of Medicine, Kurume University, Kurume, Fukuoka, 830-0011, Japan

5 Fujitsu Kyushu Systems LTD, Fukuoka, Fukuoka 814-8589, Japan

6 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan

7 Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, 277-8561, Japan

8 Department of Gastroenterology, Graduate School of Medicine, Kobe University, Chuou-ku, Kobe, Hyogo, 650-0017, Japan

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BMC Microbiology 2011, 11:104  doi:10.1186/1471-2180-11-104

Published: 16 May 2011



The genome of Helicobacter pylori, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian H. pylori genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains.


A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including oipA, hopMN, babABC, sabAB and vacA-2) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (tipĪ±), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (miaA, tilS), a DNA recombinase/exonuclease that recognizes genome identity (addA), and DNA/RNA hybrid nucleases (rnhAB). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of cagA, vacA, homC (outer membrane protein), sotB (sugar transport), and a translation fidelity factor (miaA). Large divergence was seen in genes related to antibiotics: frxA (metronidazole resistance), def (peptide deformylase, drug target), and ftsA (actin-like, drug target).


These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define H. pylori East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.