title: Genome sequence of the deep-rooted Yersinia pestis strain Angola reveals new insights into the evolution and pangenome of the plague bacterium.
abstract: To gain insights into the origin and genome evolution of the plague bacterium Yersinia pestis, we have sequenced the deep-rooted strain Angola, a virulent Pestoides isolate. Its ancient nature makes this atypical isolate of particular importance in understanding the evolution of plague pathogenicity. Its chromosome features a unique genetic make-up intermediate between modern Y. pestis isolates and its evolutionary ancestor, Y. pseudotuberculosis. Our genotypic and phenotypic analyses led us to conclude that Angola belongs to one of the most ancient Y. pestis lineages thus far sequenced. The mobilome carries the first reported chimeric plasmid combining the two species-specific virulence plasmids. Genomic findings were validated in virulence assays demonstrating that its pathogenic potential is distinct from modern Y. pestis isolates. Human infection with this particular isolate would not be diagnosed by the standard clinical tests, as Angola lacks the plasmid-borne capsule, and a possible emergence of this genotype raises major public health concerns. To assess the genomic plasticity in Y. pestis, we investigated the global gene reservoir and estimated the pangenome at 4,844 unique protein-coding genes. As shown by the genomic analysis of this evolutionary key isolate, we found that the genomic plasticity within Y. pestis clearly was not as limited as previously thought, which is strengthened by the detection of the largest number of isolate-specific single-nucleotide polymorphisms (SNPs) currently reported in the species. This study identified numerous novel genetic signatures, some of which seem to be intimately associated with plague virulence. These markers are valuable in the development of a robust typing system critical for forensic, diagnostic, and epidemiological studies.
authors.affiliation: Institute for Genome Sciences and Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Eppinger
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Worsham
authors.forename: Mikeljon P
authors.initials: MP
authors.lastname: Nikolich
authors.forename: David R
authors.initials: DR
authors.lastname: Riley
authors.forename: Yinong
authors.initials: Y
authors.lastname: Sebastian
authors.forename: Sherry
authors.initials: S
authors.lastname: Mou
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.forename: Luther E
authors.initials: LE
authors.lastname: Lindler
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D005075:Biological Evolution; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005838:Genotype; D014943:Global Health; D006168:Guinea Pigs; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000453:epidemiology / Q000382:microbiology*; D010957:Plasmids / Q000235:genetics; D014774:Virulence; D015010:Yersinia pestis / Q000145:classification* / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins