title: Natural selection and evolution of streptococcal virulence genes involved in tissue-specific adaptations.
abstract: The molecular mechanisms underlying niche adaptation in bacteria are not fully understood. Primary infection by the pathogen group A streptococcus (GAS) takes place at either the throat or the skin of its human host, and GAS strains differ in tissue site preference. Many skin-tropic strains bind host plasminogen via the plasminogen-binding group A streptococcal M protein (PAM) present on the cell surface; inactivation of genes encoding either PAM or streptokinase (a plasminogen activator) leads to loss of virulence at the skin. Unlike PAM, which is present in only a subset of GAS strains, the gene encoding streptokinase (ska) is present in all GAS isolates. In this study, the evolution of the virulence genes known to be involved in skin infection was examined. Most genetic diversity within ska genes was localized to a region encoding the plasminogen-docking domain (beta-domain). The gene encoding PAM displayed strong linkage disequilibrium (P << 0.01) with a distinct phylogenetic cluster of the ska beta-domain-encoding region. Yet, ska alleles of distant taxa showed a history of intragenic recombination, and high intrinsic levels of recombination were found among GAS strains having different tissue tropisms. The data suggest that tissue-specific adaptations arise from epistatic coselection of bacterial virulence genes. Additional analysis of ska genes showed that approximately 4% of the codons underwent strong diversifying selection. Horizontal acquisition of one ska lineage from a commensal Streptococcus donor species was also evident. Together, the data suggest that new phenotypes can be acquired through interspecies recombination between orthologous genes, while constrained functions can be preserved; in this way, orthologous genes may provide a rich and ready source for new phenotypes and thereby play a facilitating role in the emergence of new niche adaptations in bacteria.
authors.affiliation: Department of Ecology & Evolutionary Biology, Yale University, New Haven, Connecticut, USA.
authors.forename: Awdhesh
authors.initials: A
authors.lastname: Kalia
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bessen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D012867:Skin / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity*; D013300:Streptokinase / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C084529:plasminogen-binding protein, bacteria; D013300:Streptokinase