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Evolutionary history of the Clostridium difficile pathogenicity Locus
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Dingle, Kate E., Elliott, Briony, Robinson, Esther, Griffiths, David, Eyre, David W., Stoesser, Nicole, Vaughan, Alison, Golubchik, Tanya, Fawley, Warren N., Wilcox, Mark H., Peto, Timothy E., Walker, A. Sarah, Riley, Thomas V., Crook, Derrick W. and Didelot, Xavier (2013) Evolutionary history of the Clostridium difficile pathogenicity Locus. Genome Biology and Evolution, 6 (1). pp. 36-52. doi:10.1093/gbe/evt204 ISSN 1759-6653.
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Official URL: http://dx.doi.org/10.1093/gbe/evt204
Abstract
The symptoms of Clostridium difficile infection are caused by toxins expressed from its 19 kb pathogenicity locus (PaLoc). Stable integration of the PaLoc is suggested by its single chromosomal location and the clade specificity of its different genetic variants. However, the PaLoc is variably present, even among closely related strains, and thus resembles a mobile genetic element. Our aim was to explain these apparently conflicting observations by reconstructing the evolutionary history of the PaLoc. Phylogenetic analyses and annotation of the regions spanning the PaLoc were performed using C. difficile population-representative genomes chosen from a collection of 1,693 toxigenic (PaLoc present) and nontoxigenic (PaLoc absent) isolates. Comparison of the core genome and PaLoc phylogenies demonstrated an eventful evolutionary history, with distinct PaLoc variants acquired clade specifically after divergence. In particular, our data suggest a relatively recent PaLoc acquisition in clade 4. Exchanges and losses of the PaLoc DNA have also occurred, via long homologous recombination events involving flanking chromosomal sequences. The most recent loss event occurred ∼30 years ago within a clade 1 genotype. The genetic organization of the clade 3 PaLoc was unique in containing a stably integrated novel transposon (designated Tn6218), variants of which were found at multiple chromosomal locations. Tn6218 elements were Tn916-related but nonconjugative and occasionally contained genes conferring resistance to clinically relevant antibiotics. The evolutionary histories of two contrasting but clinically important genetic elements were thus characterized: the PaLoc, mobilized rarely via homologous recombination, and Tn6218, mobilized frequently through transposition.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Journal or Publication Title: | Genome Biology and Evolution | ||||||
Publisher: | Oxford University Press | ||||||
ISSN: | 1759-6653 | ||||||
Official Date: | 11 December 2013 | ||||||
Dates: |
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Volume: | 6 | ||||||
Number: | 1 | ||||||
Page Range: | pp. 36-52 | ||||||
DOI: | 10.1093/gbe/evt204 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) |
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