TY - JOUR
T1 - Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis
AU - Vogler, Amy J.
AU - Keys, Christine E.
AU - Allender, Christopher
AU - Bailey, Ira
AU - Girard, Jessica
AU - Pearson, Talima
AU - Smith, Kimothy L.
AU - Wagner, David M.
AU - Keim, Paul
N1 - Funding Information:
We thank Dr. May Chu from the Centers for Disease Control for providing the A1122 strain. We thank M. Schriefer, J. Petersen, K. Kubota, and M. Stanley from the Centers for Disease Control for sending us many of our Y. pestis DNAs that are included in our MLVA database. This work was supported by the Department of Energy NN20 CBNP, the Department of Homeland Security, the National Institutes of Health General Medical Sciences, and the Cowden Endowment in Microbiology.
PY - 2007/3/1
Y1 - 2007/3/1
N2 - VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing ∼96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.
AB - VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing ∼96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.
KW - Maximum likelihood analysis
KW - Microbial forensics
KW - Mutation rate
KW - Plague
KW - VNTR
KW - Yersinia pestis
UR - http://www.scopus.com/inward/record.url?scp=33846661637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846661637&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2006.11.007
DO - 10.1016/j.mrfmmm.2006.11.007
M3 - Article
C2 - 17161849
AN - SCOPUS:33846661637
SN - 0027-5107
VL - 616
SP - 145
EP - 158
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -