title: Whole-genome association study on tissue tropism phenotypes in group A Streptococcus.
abstract: Group A Streptococcus (GAS) has a rich evolutionary history of horizontal transfer among its core genes. Yet, despite extensive genetic mixing, GAS strains have discrete ecological phenotypes. To further our understanding of the molecular basis for ecological phenotypes, comparative genomic hybridization of a set of 97 diverse strains to a GAS pangenome microarray was undertaken, and the association of accessory genes with emm genotypes that define tissue tropisms for infection was determined. Of the 22 nonprophage accessory gene regions (AGRs) identified, only 3 account for all statistically significant linkage disequilibrium among strains having the genotypic biomarkers for throat versus skin infection specialists. Networked evolution and population structure analyses of loci representing each of the AGRs reveal that most strains with the skin specialist and generalist biomarkers form discrete clusters, whereas strains with the throat specialist biomarker are highly diverse. To identify coinherited and coselected accessory genes, the strength of genetic associations was determined for all possible pairwise combinations of accessory genes among the 97 GAS strains. Accessory genes showing very strong associations provide the basis for an evolutionary model, which reveals that a major transition between many throat and skin specialist haplotypes correlates with the gain or loss of genes encoding fibronectin-binding proteins. This study employs a novel synthesis of tools to help delineate the major genetic changes associated with key adaptive shifts in an extensively recombined bacterial species.
authors.affiliation: New York Medical College, Department of Microbiology & Immunology, Valhalla, NY 10595, USA. debra_bessen@nymc.edu
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bessen
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kumar
authors.forename: Gerod S
authors.initials: GS
authors.lastname: Hall
authors.forename: David R
authors.initials: DR
authors.lastname: Riley
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Sergio
authors.initials: S
authors.lastname: Lizano
authors.forename: Candace N
authors.initials: CN
authors.lastname: Ford
authors.forename: W Michael
authors.initials: WM
authors.lastname: McShan
authors.forename: Scott V
authors.initials: SV
authors.lastname: Nguyen
authors.forename: Julie C
authors.initials: JC
authors.lastname: Dunning Hotopp
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010614:Pharynx / Q000382:microbiology; D010802:Phylogeny; D012867:Skin / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018523:Tropism
chemical_list: D001426:Bacterial Proteins