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Research Paper |
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, L-441, 7000 East Avenue, Livermore, CA 94550, USA1
United States Army Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA2
Author for correspondence: Gary L. Andersen. Tel: +1 925 423 2525. Fax: +1 925 422 2282. e-mail: Andersen2{at}LLNL.GOV
Yersinia pestis, the causative agent of bubonic plague, emerged recently (<20000 years ago) as a clone of Yersinia pseudotuberculosis. There is scant evidence of genome diversity in Y. pestis, although it is possible to differentiate three biovars (antiqua, mediaevalis or orientalis) based on two biochemical tests. There are a few examples of restriction fragment length polymorphisms (RFLPs) within Y. pestis; however, their genetic basis is poorly understood. In this study, six difference regions (DFRs) were identified in Y. pestis, by using subtractive hybridization, which ranged from 4·6 to 19 kb in size. Four of the DFRs are flanked by insertion sequences, and their sequences show similarity to bacterial genes encoding proteins for flagellar synthesis, ABC transport, insect toxicity and bacteriophage functions. The presence or absence of these DFRs (termed the DFR profile) was demonstrated in 78 geographically diverse strains of Y. pestis. Significant genome plasticity was observed among these strains and suggests the acquisition and deletion of these DNA regions during the recent evolution of Y. pestis. Y. pestis biovar orientalis possesses DFR profiles that are different from antiqua and mediaevalis biovars, reflecting the recent origins of this biovar. Whereas some DFR profiles are specific for antiqua and mediaevalis, some DFR profiles are shared by both biovars. Furthermore, the progenitor of Y. pestis, Y. pseudotuberculosis (an enteric pathogen), possesses its own DFR profile. The DFR profiles detailed here demonstrate genome plasticity within Y. pestis, and they imply evolutionary relationships among the three biovars of Y. pestis, as well as between Y. pestis and Y. pseudotuberculosis.
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Abbreviations: DFR, difference region; RFLP, restriction fragment length polymorphism; SSH, suppression subtractive hybridization
The GenBank accession numbers for the sequences reported in this paper can be found in Table 1; the GenBank accession number for DFR4 is AF426171.
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