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High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi

Nature Genetics volume 40, pages 987993 (2008) | Download Citation


Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. We generated whole-genome sequences for 19 Typhi isolates using 454 (Roche) and Solexa (Illumina) technologies. Isolates, including the previously sequenced CT18 and Ty2 isolates, were selected to represent major nodes in the phylogenetic tree. Comparative analysis showed little evidence of purifying selection, antigenic variation or recombination between isolates. Rather, evolution in the Typhi population seems to be characterized by ongoing loss of gene function, consistent with a small effective population size. The lack of evidence for antigenic variation driven by immune selection is in contrast to strong adaptive selection for mutations conferring antibiotic resistance in Typhi. The observed patterns of genetic isolation and drift are consistent with the proposed key role of asymptomatic carriers of Typhi as the main reservoir of this pathogen, highlighting the need for identification and treatment of carriers.

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This work was supported by the Wellcome Trust. M.A. and C.J.M. are supported in Ireland by grant 05/FE1/B882 from the Scientific Foundation Ireland and C.J.M. was supported in Berlin by a Wellcome Trust grant to J. Farrar. We gratefully acknowledge the support of the Sanger Institute core sequencing and informatics groups. Isolates were provided by the Oxford University Clinical Research Unit (CT18, J185SM, AG3); B. Holmes at the National Collection of Type Cultures (M223); the Wellcome Trust Sanger Institute (404ty, Ty2); and F.-X.W. (all other isolates).

Author information

Author notes

    • Ian Goodhead

    Present address: School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK.


  1. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

    • Kathryn E Holt
    • , Julian Parkhill
    • , Ian Goodhead
    • , Richard Rance
    • , Stephen Baker
    • , John Wain
    •  & Gordon Dougan
  2. Environmental Research Institute, University College Cork, Lee Road, Cork, Ireland.

    • Camila J Mazzoni
    •  & Mark Achtman
  3. Max-Planck-Institut für Infektionsbiologie, Department of Molecular Biology, Charitéplatz 1, 10117, Berlin, Germany.

    • Camila J Mazzoni
    • , Philippe Roumagnac
    •  & Mark Achtman
  4. Université Mixte de Recherche 6191 Centre National de la Recherche Scientifique - Commissariat à l'Énergie Atomique-Aix-Marseille Université, Commissariat à l'Énergie Atomique Cadarache, 13108 Saint Paul lez Durance, France.

    • Philippe Roumagnac
  5. Institut Pasteur, Laboratoire des Bactéries Pathogènes Entériques, 28 rue du docteur Roux, 75724 Paris cedex 15, France.

    • François-Xavier Weill
  6. Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam.

    • Stephen Baker
    •  & Christiane Dolecek
  7. Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.

    • Duncan J Maskell


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G.D., J.P., M.A., P.R. and J.W. designed the study; F.-X.W. and C.D. contributed isolates for analysis; I.G. and R.R. performed 454 and Solexa sequencing; K.E.H. and S.B. performed validation experiments; D.J.M. co-supervises the PhD studies of K.E.H. and contributed to experimental design; K.E.H. and C.J.M. analysed data and K.E.H., J.P., P.R. and G.D. wrote the manuscript.

Corresponding author

Correspondence to Kathryn E Holt.

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