Journal of Molecular Biology
Regular articleConcerted evolution between duplicated genetic elements in Helicobacter pylori1
Introduction
Concerted evolution represents the co-evolution of DNA sequences within members of a related family, such that they maintain high levels of similarity among themselves, as they diverge from the same family members in other species or strains.1, 2 Numerous examples of concerted evolution exist among gene family members from eukaryotic organisms; however, there have been fewer examples of concerted evolution in bacteria.3, 4, 5, 6 Gene conversion is one mechanism facilitating concerted evolution, as it involves the replacement of one family member by the other, such as occurs with the pilin genes in Neisseria gonorrhoeae.7, 8
Helicobacter pylori is a microaerophilic, Gram-negative bacterial species that colonizes the human stomach, and plays a role in the development of peptic ulcer disease and gastric adenocarcinoma.9 The H. pylori genome contains a 32 member family of outer membrane proteins (OMP family), including babA and babB, with substantial N and C-terminal identity, likely the result of gene duplication events followed by the diversification of individual family members.10, 11, 12 Gene duplications can lead to their own long-term maintenance, the creation of new gene functions, silencing of duplicated copies, or to molecular interactions preventing their diversification.1, 3, 4, 13, 14, 15 Within the H. pylori OMP family, both new gene function and long-term maintenance of duplicate copies occur.12
To better understand the evolution of the H. pylori OMP family, we studied babA and babB from strains from several geographic locales. BabA is an adhesin, responsible for binding to the human blood group antigen Lewis B.16 Prior studies have suggested that the 5′ and 3′ regions of babA and babB have evolved similarly, that the babA and babB central portions possess different allele groups, and that the OMP family may be subject to gene conversion events.12, 16, 17, 18 We used a sliding window approach to identify segments of both genes subject to differential selective pressures, followed by examination of phylogenetic relationships and nucleotide substitution patterns within the identified segments. We sought to explore whether babA and babB segments are evolving in concert, to develop an experimental system to assess gene conversion in H. pylori, and to determine whether parallel patterns of evolution exist for both genes.
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Geographic variation within babA and babB
We determined H. pylori babA and babB sequences from 23 strains, representing a variety of babA and babB allele groups, from several geographic locales (Table 1).17 As expected, phylogenetic analysis shows independent branches for babA and babB (Figure 1), and for each gene there is a clear separation between USA and Asian strains. Within each grouping of Asian and Western strains, the allele group status of each strain appears to be the major determinant of position. The babB sequences from
Discussion
Analysis of the outer membrane protein family (OMP family) provides additional insights into H. pylori evolution. Although recombination has been important in the evolution of other H. pylori genes, including vacA and flaA, possible recombinational events involving babA and babB have not obscured evidence of geographic isolation of the strains in this study.24, 25 That there exists a phylogenetic division of the Asian and Western babA and babB sequences suggests the isolation of the H. pylori
Strains and growth conditions
A total of 23 H. pylori strains were obtained from patients from several locales (Table 1). Strains were cultured at 37°C in a 5% (v/v) CO2 atmosphere on trypticase soy agar plates with 5% (v/v) sheep blood, and stored frozen at −70°C. Genomic DNA was prepared from each strain after 48-72 hours growth on trypticase soy agar plates with 5% sheep blood, and vacA allelic types and the presence of cagA were determined by PCR using established primers.35, 36, 37, 38
Nucleotide sequence analysis of babA and babB
Sequences of babA were amplified
Acknowledgements
This work was supported, in part, by the National Institutes of Health (RO1 DK53707, RO1 GM63270 and the Cancer Center Core grant CA 68485), the Medical Scientist Training Program, the UNCF-Merck Science Initiative, and the Gates Millenium Scholars Program. We thank Richard Meinersmann and Carolina Arias for their contributions.
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Edited by J. Miller