title: Simple sequence repeats and genome plasticity in Streptococcus agalactiae.
abstract: Simple sequence repeats (SSRs) and their role in phase variation have been extensively studied in Gram-negative organisms, where they have been associated with antigenic variation and other adaptation strategies. In this study, we apply comparative genomics in order to find evidence of slipped-strand mispairing in the human Gram-positive pathogen Streptococcus agalactiae. In two consecutive screenings, 2,233 (650 + 1,583) SSRs were identified in our reference genome 2603V/R, and these loci were examined in seven other S. agalactiae genomes. A total of 56 SSR loci were found to exhibit variation, where gain or loss of repeat units was observed in at least one other genome, resulting in aberrant genotypes. Homopolymeric adenine tracts predominated among the repeats that varied. Positional analysis revealed that long polyadenine tracts were overrepresented in the 5' ends of open reading frames (ORFs) and underrepresented in the 3' ends. Repeat clustering in ORFs was also examined, and the highest degree of clustering was observed for a capsule biosynthesis gene and a pilus sortase. A statistical analysis of observed over expected ratios suggested a selective pressure against long homopolymeric tracts. Altered phenotypes were verified for three genes encoding surface-attached proteins, in which frameshifts or fusions led to truncation of proteins and/or affected surface localization through loss or gain of the cell wall sorting signal. The data suggest that SSRs contributes to genome plasticity in S. agalactiae but that the bet-hedging strategy is different from Gram-negative organisms.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy. robert.janulczyk@novartis.com
authors.forename: Robert
authors.initials: R
authors.lastname: Janulczyk
authors.forename: Vega
authors.initials: V
authors.lastname: Masignani
authors.forename: Domenico
authors.initials: D
authors.lastname: Maione
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
mesh_terms: D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013292:Streptococcus agalactiae / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial