Parallel independent evolution of pathogenicity within the genus Yersinia

Sandra Reuter; Thomas R. Connor; Lars Barquist; Danielle Walker; Theresa Feltwell; Simon R. Harris; Maria Fookes; Miquette E. Hall; Nicola K. Petty; Thilo M. Fuchs; Jukka Corander; Muriel Dufour; Tamara Ringwood; Cyril Savin; Christiane Bouchier; Liliane Martin; Minna Miettinen; Mikhail Shubin; Julia M. Riehm; Riikka Laukkanen-Ninios; Leila M. Sihvonen; Anja Siitonen; Mikael Skurnik; Juliana Pfrimer Falcão; Hiroshi Fukushima; Holger C. Scholz; Michael B. Prentice; Brendan W. Wren; Julian Parkhill; Elisabeth Carniel; Mark Achtman; Alan McNally; Nicholas R. Thomson

doi:10.1073/pnas.1317161111

Edited by Ralph R. Isberg, Howard Hughes Medical Institute and Tufts University School of Medicine, Boston, MA, and approved March 21, 2014 (received for review October 2, 2013)

Significance

Our past understanding of pathogen evolution has been fragmented because of tendencies to study human clinical isolates. To understand the evolutionary trends of pathogenic bacteria though, we need the context of their nonpathogenic relatives. Our unique and detailed dataset allows description of the parallel evolution of two key human pathogens: the causative agents of plague and Yersinia diarrhea. The analysis reveals an emerging pattern where few virulence-related functions are found in all pathogenic lineages, representing key “foothold” moments that mark the emergence of these pathogens. Functional gene loss and metabolic streamlining are equally complementing the evolution of Yersinia across the pathogenic spectrum.

Abstract

The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens.

Footnotes

↵¹S.R. and T.R.C. contributed equally to this work.
↵²To whom correspondence should be addressed. E-mail: nrt{at}sanger.ac.uk.

Author contributions: S.R., T.R.C., B.W.W., J.P., M.A., A.M., and N.R.T. designed research; S.R., T.R.C., L.B., D.W., T.F., S.R.H., M.F., M.E.H., N.K.P., J.C., M.M., M. Shubin, and N.R.T. performed research; T.M.F., M.D., T.R., C.S., C.B., L.M., J.M.R., R.L.-N., L.M.S., A.S., J.P.F., H.F., and H.C.S. were involved in isolate collection and typing; S.R., T.R.C., L.B., D.W., S.R.H., M.F., M.E.H., N.K.P., J.C., M.M., M. Shubin, and N.R.T. analyzed data; and S.R., T.R.C., L.B., S.R.H., T.M.F., M. Skurnik, M.B.P., B.W.W., J.P., E.C., M.A., A.M., and N.R.T. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequences reported in this paper have been deposited in the European Nucleotide Archive (ENA study nos. PRJEB2116, PRJEB2117) GenBank and SRA numbers are given in Table S1.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1317161111/-/DCSupplemental.

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