Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes.
Helicobacter pylori infection is a risk factor for the development of gastric adenocarcinoma, a disease that has a high incidence in East Asia. Genes that are highly divergent in East Asian H. pylori strains compared to non-Asian strains are predicted to encode proteins that differ in functional act...
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doaj-89d341403dec422e81557c249e8888132020-11-25T01:33:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5512010.1371/journal.pone.0055120Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes.Stacy S DuncanPieter L ValkMark S McClainCarrie L ShafferJason A MetcalfSeth R BordensteinTimothy L CoverHelicobacter pylori infection is a risk factor for the development of gastric adenocarcinoma, a disease that has a high incidence in East Asia. Genes that are highly divergent in East Asian H. pylori strains compared to non-Asian strains are predicted to encode proteins that differ in functional activity and could represent novel determinants of virulence. To identify such proteins, we undertook a comparative analysis of sixteen H. pylori genomes, selected equally from strains classified as East Asian or non-Asian. As expected, the deduced sequences of two known virulence determinants (CagA and VacA) are highly divergent, with 77% and 87% mean amino acid sequence identities between East Asian and non-Asian groups, respectively. In total, we identified 57 protein sequences that are highly divergent between East Asian and non-Asian strains, but relatively conserved within East Asian strains. The most highly represented functional groups are hypothetical proteins, cell envelope proteins and proteins involved in DNA metabolism. Among the divergent genes with known or predicted functions, population genetic analyses indicate that 86% exhibit evidence of positive selection. McDonald-Kreitman tests further indicate that about one third of these highly divergent genes, including cagA and vacA, are under diversifying selection. We conclude that, similar to cagA and vacA, most of the divergent genes identified in this study evolved under positive selection, and represent candidate factors that may account for the disproportionately high incidence of gastric cancer associated with East Asian H. pylori strains. Moreover, these divergent genes represent robust biomarkers that can be used to differentiate East Asian and non-Asian H. pylori strains.http://europepmc.org/articles/PMC3561388?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stacy S Duncan Pieter L Valk Mark S McClain Carrie L Shaffer Jason A Metcalf Seth R Bordenstein Timothy L Cover |
spellingShingle |
Stacy S Duncan Pieter L Valk Mark S McClain Carrie L Shaffer Jason A Metcalf Seth R Bordenstein Timothy L Cover Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. PLoS ONE |
author_facet |
Stacy S Duncan Pieter L Valk Mark S McClain Carrie L Shaffer Jason A Metcalf Seth R Bordenstein Timothy L Cover |
author_sort |
Stacy S Duncan |
title |
Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. |
title_short |
Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. |
title_full |
Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. |
title_fullStr |
Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. |
title_full_unstemmed |
Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. |
title_sort |
comparative genomic analysis of east asian and non-asian helicobacter pylori strains identifies rapidly evolving genes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Helicobacter pylori infection is a risk factor for the development of gastric adenocarcinoma, a disease that has a high incidence in East Asia. Genes that are highly divergent in East Asian H. pylori strains compared to non-Asian strains are predicted to encode proteins that differ in functional activity and could represent novel determinants of virulence. To identify such proteins, we undertook a comparative analysis of sixteen H. pylori genomes, selected equally from strains classified as East Asian or non-Asian. As expected, the deduced sequences of two known virulence determinants (CagA and VacA) are highly divergent, with 77% and 87% mean amino acid sequence identities between East Asian and non-Asian groups, respectively. In total, we identified 57 protein sequences that are highly divergent between East Asian and non-Asian strains, but relatively conserved within East Asian strains. The most highly represented functional groups are hypothetical proteins, cell envelope proteins and proteins involved in DNA metabolism. Among the divergent genes with known or predicted functions, population genetic analyses indicate that 86% exhibit evidence of positive selection. McDonald-Kreitman tests further indicate that about one third of these highly divergent genes, including cagA and vacA, are under diversifying selection. We conclude that, similar to cagA and vacA, most of the divergent genes identified in this study evolved under positive selection, and represent candidate factors that may account for the disproportionately high incidence of gastric cancer associated with East Asian H. pylori strains. Moreover, these divergent genes represent robust biomarkers that can be used to differentiate East Asian and non-Asian H. pylori strains. |
url |
http://europepmc.org/articles/PMC3561388?pdf=render |
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