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MBE Advance Access published online on August 4, 2007

Molecular Biology and Evolution, doi:10.1093/molbev/msm163
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Recent Gene Conversions Between Duplicated Glutamate Decarboxylase Genes (gadA and gadB) in Pathogenic Escherichia coli

Teresa M. Bergholz*, Cheryl L. Tarr{dagger}, Lisa. M. Christensen{ddagger}, David J. Betting{ddagger} and Thomas S. Whittam*

* Microbial Evolution Laboratory, National Food Safety & Toxicology Center, Michigan State University, East Lansing, MI 48824
{dagger} Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA,30333
{ddagger} Department of Biology, Pennsylvania State University, University Park, PA 16802, USA

Corresponding author. Mailing address: NFSTC, 165 Food Safety & Toxicology Building, Michigan State University, East Lansing, MI 48824. Phone: (517) 432-3100 ext 178. Fax: (517) 432-2310. Email: whittam{at}msu.edu

Received for publication May 13, 2007. Revision received July 29, 2007. Accepted for publication July 31, 2007.

Escherichia coli have evolved adaptive systems to resist strongly acidic habitats in part through the production of two biochemically identical isoforms of glutamate decarboxylase, encoded by the gadA and gadB genes. These genes occur in E. coli and other members of the genospecies (e.g. Shigella spp.) and originated as part of a genomic fitness island acquired early in Escherichia evolution. The present duplicated gad loci are widely spaced on the E. coli chromosome and the two genes are 97% similar in sequence. Comparison of the nucleotide sequences of the gadA and gadB in 16 strains of pathogenic E. coli revealed 3.8% and 5.0% polymorphism in the two genes, respectively. Alignment of the homologous genes identified a total of 120 variable sites, including 21 fixed nucleotide differences between the loci within the first 82 codons of the genes. Twenty-three phylogenetically informative sites were polymorphic for the same nucleotides in both genes suggesting recent gene conversions or intergenic recombination. Phylogenetic analysis based on the synonymous substitutions per synonymous site indicated two cases in which specific gadA and gadB alleles were more closely related to one another than to other alleles at the corresponding locus. The results indicate that at least three gene conversion events have occurred after the gad gene duplication in the evolution of E. coli. Despite multiple gene conversion events, the upstream regulatory regions and the 5' end of each gene remains distinct, suggesting that maintaining functionally different gad genes is important in this acid resistance mechanism in pathogenic E. coli.


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