title: Evolutionary dynamics of Clostridium difficile over short and long time scales.
abstract: Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. However, the genetic basis for the emergence of C. difficile as a human pathogen is unclear. Whole genome sequencing was used to analyze genetic variation and virulence of a diverse collection of thirty C. difficile isolates, to determine both macro and microevolution of the species. Horizontal gene transfer and large-scale recombination of core genes has shaped the C. difficile genome over both short and long time scales. Phylogenetic analysis demonstrates C. difficile is a genetically diverse species, which has evolved within the last 1.1-85 million years. By contrast, the disease-causing isolates have arisen from multiple lineages, suggesting that virulence evolved independently in the highly epidemic lineages.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sebaihia
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stabler
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Dawson
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Martin
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Helena M B
authors.initials: HM
authors.lastname: Seth-Smith
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Richard
authors.initials: R
authors.lastname: Rance
authors.forename: Karen
authors.initials: K
authors.lastname: Brooks
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Christine
authors.initials: C
authors.lastname: Burrows
authors.forename: Louise
authors.initials: L
authors.lastname: Clark
authors.forename: Craig
authors.initials: C
authors.lastname: Corton
authors.forename: Vicky
authors.initials: V
authors.lastname: Murray
authors.forename: Graham
authors.initials: G
authors.lastname: Rose
authors.forename: Scott
authors.initials: S
authors.lastname: Thurston
authors.forename: Andries
authors.initials: A
authors.lastname: van Tonder
authors.forename: Danielle
authors.initials: D
authors.lastname: Walker
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
mesh_terms: D016360:Clostridioides difficile / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D018014:Gene Transfer Techniques; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013997:Time Factors; D014774:Virulence