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Journal of Bacteriology, June 2006, p. 4453-4463, Vol. 188, No. 12
0021-9193/06/$08.00+0     doi:10.1128/JB.00124-06

Complete Genome Sequence of Yersinia pestis Strains Antiqua and Nepal516: Evidence of Gene Reduction in an Emerging Pathogen

Patrick S. G. Chain,^1,2, Ping Hu,^3, Stephanie A. Malfatti,^1,2 Lyndsay Radnedge,^1, Frank Larimer,^2,4 Lisa M. Vergez,^1,2 Patricia Worsham,⁵ May C. Chu,⁶ and Gary L. Andersen^3*

Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550,¹ Joint Genome Institute, Walnut Creek, California,² Center for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, California 94720,³ Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831,⁴ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,⁵ Centers for Disease Control and Prevention, Fort Collins, Colorado 80522⁶

Received 23 January 2006/ Accepted 3 April 2006

Yersinia pestis, the causative agent of bubonic and pneumonic plagues, has undergone detailed study at the molecular level. To further investigate the genomic diversity among this group and to help characterize lineages of the plague organism that have no sequenced members, we present here the genomes of two isolates of the "classical" antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua and Nepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open reading frames, respectively. Though both strains belong to one of the three classical biovars, they represent separate lineages defined by recent phylogenetic studies. We compare all five currently sequenced Y. pestis genomes and the corresponding features in Yersinia pseudotuberculosis. There are strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. We found 453 single nucleotide polymorphisms in protein-coding regions, which were used to assess the evolutionary relationships of these Y. pestis strains. Gene reduction analysis revealed that the gene deletion processes are under selective pressure, and many of the inactivations are probably related to the organism's interaction with its host environment. The results presented here clearly demonstrate the differences between the two biovar antiqua lineages and support the notion that grouping Y. pestis strains based strictly on the classical definition of biovars (predicated upon two biochemical assays) does not accurately reflect the phylogenetic relationships within this species. A comparison of four virulent Y. pestis strains with the human-avirulent strain 91001 provides further insight into the genetic basis of virulence to humans.

Supplemental material for this article may be found at http://jb.asm.org/.

These authors contributed equally to this work.

Present address: Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA 94080.

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