Complete genome sequence of Yersinia pestis strains Antiqua and Nepal516: evidence of gene reduction in an emerging pathogen

Abstract

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.

FIG. 1.

Circular representation of the strain Antiqua (A) and strain Nepal516 (B) chromosomes. The different rings represent (from outer to inner) all genes color-coded by functional category (rings 1 and 2), IS elements (IS100, IS285, IS1541, IS1661) (rings 3 and 4), deviation from average G+C content (ring 5), and GC skew (ring 6).

FIG. 2.

Phylogenetic ordering of Yersinia by SNP analysis. The number of sSNPs and the number of nsSNPs (in parentheses) are illustrated at the corresponding positions.

FIG. 3.

Functional distribution of genes bearing SNPs. The numbers of genome-specific nsSNPs (A) and sSNPs (B) were grouped into COG functional classes. These were subcategorized based on what genome(s) they were found in (light orange, 91001; red, CO92; dark red, KIM; blue, Antiqua; light blue, Nepal516; green, KIM and Nepal516; and yellow, Antiqua and CO92). C, energy production; D, cell division; E, amino acid metabolism; F, nucleotide metabolism; G, carbohydrate metabolism; H, coenzyme metabolism; I, lipid metabolism; J, translation; K, transcription; L, DNA replication or repair; M, cell wall/membrane biogenesis; N, cell motility; O, posttranslational modification; P, inorganic ion metabolism; Q, secondary metabolite biosynthesis, transport and catabolism; R, general function prediction only; S, function unknown; T, signal transduction; U, intracellular trafficking and secretion; V, defense mechanism.