title: High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi.
abstract: 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. kh2@sanger.ac.uk
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Camila J
authors.initials: CJ
authors.lastname: Mazzoni
authors.forename: Philippe
authors.initials: P
authors.lastname: Roumagnac
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.forename: Ian
authors.initials: I
authors.lastname: Goodhead
authors.forename: Richard
authors.initials: R
authors.lastname: Rance
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D001435:Bacteriophages / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D044404:Genomic Islands; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D012485:Salmonella typhi / Q000145:classification / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D014435:Typhoid Fever / Q000382:microbiology