Genome sequence of Yersinia pestis KIM

Abstract

We present the complete genome sequence of Yersinia pestis KIM, the etiologic agent of bubonic and pneumonic plague. The strain KIM, biovar Mediaevalis, is associated with the second pandemic, including the Black Death. The 4.6-Mb genome encodes 4,198 open reading frames (ORFs). The origin, terminus, and most genes encoding DNA replication proteins are similar to those of Escherichia coli K-12. The KIM genome sequence was compared with that of Y. pestis CO92, biovar Orientalis, revealing homologous sequences but a remarkable amount of genome rearrangement for strains so closely related. The differences appear to result from multiple inversions of genome segments at insertion sequences, in a manner consistent with present knowledge of replication and recombination. There are few differences attributable to horizontal transfer. The KIM and E. coli K-12 genome proteins were also compared, exposing surprising amounts of locally colinear "backbone," or synteny, that is not discernible at the nucleotide level. Nearly 54% of KIM ORFs are significantly similar to K-12 proteins, with conserved housekeeping functions. However, a number of E. coli pathways and transport systems and at least one global regulator were not found, reflecting differences in lifestyle between them. In KIM-specific islands, new genes encode candidate pathogenicity proteins, including iron transport systems, putative adhesins, toxins, and fimbriae.

FIG. 1.

Circular genome map of KIM. The KIM genome has 4,198 ORFs, 2,254 of which are homologous to K-12 genes at the protein level (40% identity; alignments including at least 60% of both proteins). The outer circle shows the distribution of backbone ORFs: ORFs with the same replication orientations and on the same replichores (blue); ORFs with the same replication orientations but on different replichores (green); and ORFs with different replication orientations (red). The short ticks represent ORFs that have moved out of their normal K-12 context range. The second circle shows both the backbone (blue) and nonbackbone (pink) ORFs and their orientations. The arrows in the third and fourth circles show the locations and the orientations of tRNA (green) and rRNA (red) operons, respectively (not shown to scale). The fifth circle shows insertion element distribution: IS100 (red), IS1541A (blue), IS285 (green), and IS1661 (yellow). The short ticks represent partial IS elements. The sixth circle gives the scale in base pairs. The seventh circle shows highly skewed octamer Chi distribution: red and yellow indicate its distribution on the two DNA strands. The inner circle shows the C-G skew that is calculated for each sliding window of 10 kb along the genome. The maps were created by GenVision (DNASTAR).

FIG. 2.

Comparison of KIM and CO92 at the DNA level. The outer circles show the CO92 C-G skew. The second circle shows CO92 IS elements: IS100 (red), IS1541A (blue), IS285 (green), and IS1661 (yellow); short ticks represent partial IS elements. The third circle shows CO92 rRNA operons. The fourth circle shows the CO92 genome in 27 blocks (numbered according to KIM genome order), regions that are conserved by both locations and orientations (red), a single intrareplichore inversion region (yellow), multiple-inversion regions (various blues), and genome-specific sequences (green). The inner four circles show KIM rRNA operons, the KIM genome in blocks, KIM IS elements, and KIM C-G skew. Colors are coded as for CO92.

FIG. 3.

The most parsimonious series of inversions for each of the multiple-inversion regions (Fig. 2). Each horizontal arrow represents a DNA block (not shown to scale) and its orientation. Blue and red indicate opposite replication orientations of the same block. The replication origin and terminus are marked by a small brown downward arrow. The green crossed double arrows stand for interreplichore inversions, and the orange crossed double arrows stand for intrareplichore inversions. The small red arrows (not shown to scale) on some of the blocks indicate rRNA operon locations.

FIG. 4.

Comparison of KIM and K-12 at the protein level. (a) Synteny of KIM and K-12 genomes. The backbone genes on each genome can be arranged in three different ways: genes in the same replication orientations and on the same replichores (blue), genes in the same replication orientations but on different replichores (green), and genes in different replication orientations (red). (b) Arrangement of backbone genes. x axis, the average ori distances of orthologous genes; y axis, the offset of ori distances of orthologous genes. Colors are coded as for panel a.

FIG. 5.

Accessibility of DNA for recombination near replication forks. On the left, the theta structure of the replicating chromosome is shown, with arrows indicating that the nonreplicating DNA is bound with proteins in nucleoids (in the middle). The two replichores are colored green and blue, and a region of homology is indicated by thickened segments. A recombination event between homologous regions would result in the interreplichore inversion shown on the right.