Evolution of cagA Oncogene of Helicobacter pylori through Recombination

Helicobacter pylori is a gastric pathogen that infects half the human population and causes gastritis, ulcers, and cancer. The cagA gene product is a major virulence factor associated with gastric cancer. It is injected into epithelial cells, undergoes phosphorylation by host cell kinases, and pert...

Full description

Bibliographic Details
Main Authors:	Furuta, Yoshikazu, Yahara, Koji, Hatakeyama, Masanori, Kobayashi, Ichizo
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154945/

id	pubmed-3154945
recordtype	oai_dc
spelling	pubmed-31549452011-08-18 Evolution of cagA Oncogene of Helicobacter pylori through Recombination Furuta, Yoshikazu Yahara, Koji Hatakeyama, Masanori Kobayashi, Ichizo Research Article Helicobacter pylori is a gastric pathogen that infects half the human population and causes gastritis, ulcers, and cancer. The cagA gene product is a major virulence factor associated with gastric cancer. It is injected into epithelial cells, undergoes phosphorylation by host cell kinases, and perturbs host signaling pathways. CagA is known for its geographical, structural, and functional diversity in the C-terminal half, where an EPIYA host-interacting motif is repeated. The Western version of CagA carries the EPIYA segment types A, B, and C, while the East Asian CagA carries types A, B, and D and shows higher virulence. Many structural variants such as duplications and deletions are reported. In this study, we gained insight into the relationships of CagA variants through various modes of recombination, by analyzing all known cagA variants at the DNA sequence level with the single nucleotide resolution. Processes that occurred were: (i) homologous recombination between DNA sequences for CagA multimerization (CM) sequence; (ii) recombination between DNA sequences for the EPIYA motif; and (iii) recombination between short similar DNA sequences. The left half of the EPIYA-D segment characteristic of East Asian CagA was derived from Western type EPIYA, with Amerind type EPIYA as the intermediate, through rearrangements of specific sequences within the gene. Adaptive amino acid changes were detected in the variable region as well as in the conserved region at sites to which no specific function has yet been assigned. Each showed a unique evolutionary distribution. These results clarify recombination-mediated routes of cagA evolution and provide a solid basis for a deeper understanding of its function in pathogenesis. Public Library of Science 2011-08-11 /pmc/articles/PMC3154945/ /pubmed/21853141 http://dx.doi.org/10.1371/journal.pone.0023499 Text en Furuta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Furuta, Yoshikazu Yahara, Koji Hatakeyama, Masanori Kobayashi, Ichizo
spellingShingle	Furuta, Yoshikazu Yahara, Koji Hatakeyama, Masanori Kobayashi, Ichizo Evolution of cagA Oncogene of Helicobacter pylori through Recombination
author_facet	Furuta, Yoshikazu Yahara, Koji Hatakeyama, Masanori Kobayashi, Ichizo
author_sort	Furuta, Yoshikazu
title	Evolution of cagA Oncogene of Helicobacter pylori through Recombination
title_short	Evolution of cagA Oncogene of Helicobacter pylori through Recombination
title_full	Evolution of cagA Oncogene of Helicobacter pylori through Recombination
title_fullStr	Evolution of cagA Oncogene of Helicobacter pylori through Recombination
title_full_unstemmed	Evolution of cagA Oncogene of Helicobacter pylori through Recombination
title_sort	evolution of caga oncogene of helicobacter pylori through recombination
description	Helicobacter pylori is a gastric pathogen that infects half the human population and causes gastritis, ulcers, and cancer. The cagA gene product is a major virulence factor associated with gastric cancer. It is injected into epithelial cells, undergoes phosphorylation by host cell kinases, and perturbs host signaling pathways. CagA is known for its geographical, structural, and functional diversity in the C-terminal half, where an EPIYA host-interacting motif is repeated. The Western version of CagA carries the EPIYA segment types A, B, and C, while the East Asian CagA carries types A, B, and D and shows higher virulence. Many structural variants such as duplications and deletions are reported. In this study, we gained insight into the relationships of CagA variants through various modes of recombination, by analyzing all known cagA variants at the DNA sequence level with the single nucleotide resolution. Processes that occurred were: (i) homologous recombination between DNA sequences for CagA multimerization (CM) sequence; (ii) recombination between DNA sequences for the EPIYA motif; and (iii) recombination between short similar DNA sequences. The left half of the EPIYA-D segment characteristic of East Asian CagA was derived from Western type EPIYA, with Amerind type EPIYA as the intermediate, through rearrangements of specific sequences within the gene. Adaptive amino acid changes were detected in the variable region as well as in the conserved region at sites to which no specific function has yet been assigned. Each showed a unique evolutionary distribution. These results clarify recombination-mediated routes of cagA evolution and provide a solid basis for a deeper understanding of its function in pathogenesis.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154945/
_version_	1611470579251019776

Evolution of cagA Oncogene of Helicobacter pylori through Recombination

Similar Items