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Effect of repeat copy number on variable-number tandem repeat mutations in Escherichia coli O157:H7

Vogler, Amy J. and Keys, Christine and Nemoto, Yoshimi and Colman, Rebecca E. and Jay, Zack and Keim, Paul (2006) Effect of repeat copy number on variable-number tandem repeat mutations in Escherichia coli O157:H7. Journal of Bacteriology, 188 (12). p. 29. ISSN 1098-5530


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Publisher’s or external URL: http://dx.doi.org/10.1128/jb.00001-06


Variable-number tandem repeat (VNTR) loci have shown a remarkable ability to discriminate among isolates of the recently emerged clonal pathogen Escherichia coli O157:H7, making them a very useful molecular epidemiological tool. However, little is known about the rates at which these sequences mutate, the factors that affect mutation rates, or the mechanisms by which mutations occur at these loci. Here, we measure mutation rates for 28 VNTR loci and investigate the effects of repeat copy number and mismatch repair on mutation rate using in vitro-generated populations for 10 E. coli O157:H7 strains. We find single-locus rates as high as 7.0 x 10-4 mutations/generation and a combined 28-locus rate of 6.4 x 10-4 mutations/generation. We observed single- and multirepeat mutations that were consistent with a slipped-strand mispairing mutation model, as well as a smaller number of large repeat copy number mutations that were consistent with recombination-mediated events. Repeat copy number within an array was strongly correlated with mutation rate both at the most mutable locus, O157-10 (r² = 0.565, P = 0.0196), and across all mutating loci. The combined locus model was significant whether locus O157-10 was included (r² = 0.833, P < 0.0001) or excluded (r² = 0.452, P < 0.0001) from the analysis. Deficient mismatch repair did not affect mutation rate at any of the 28 VNTRs with repeat unit sizes of >5 bp, although a poly(G) homomeric tract was destabilized in the mutS strain. Finally, we describe a general model for VNTR mutations that encompasses insertions and deletions, single- and multiple-repeat mutations, and their relative frequencies based upon our empirical mutation rate data.

Item Type: Article
Publisher’s Statement: Copyright © 2006, American Society for Microbiology.
ID number or DOI: 10.1128/JB.00001-06
Keywords: Animals; Buffaloes; Cattle; copy number; dna mismatch repair; Dynamics; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Escherichia coli O157; Evolution; Gene deletion; Gene Dosage; Genomes; Humans; instability; loci; microsatellite mutations; Minisatellite Repeats; mismatch repair; models; Molecular epidemiology; Mutation; Mutation (Biology); mutation rates; Pathogenic microorganisms; pathogens; Plague; sequence dna; Serial Passage; yersinia-pestis
Subjects: Q Science > QR Microbiology
NAU Depositing Author Academic Status: Faculty/Staff
Department/Unit: College of Engineering, Forestry, and Natural Science > Biological Sciences
Date Deposited: 12 Oct 2015 16:25
URI: http://openknowledge.nau.edu/id/eprint/818

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