Evolutionary paths of streptococcal and staphylococcal superantigens

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pyogenes</it> (GAS) harbors several superantigens (SAgs) in the prophage region of its genome, although <it>speG</it> and <it>smez</it> are not located in this region. The diversity of SAgs is thought to arise during horizontal transfer, but their evolutionary pathways have not yet been determined. We recently completed sequencing the entire genome of <it>S. dysgalactiae</it> subsp. <it>equisimilis</it> (SDSE), the closest relative of GAS. Although <it>speG</it> is the only SAg gene of SDSE, <it>speG</it> was present in only 50% of clinical SDSE strains and <it>smez</it> in none. In this study, we analyzed the evolutionary paths of streptococcal and staphylococcal SAgs.</p> <p>Results</p> <p>We compared the sequences of the 12–60 kb <it>speG</it> regions of nine SDSE strains, five <it>speG</it>⁺ and four <it>speG</it>^<it>–</it>. We found that the synteny of this region was highly conserved, whether or not the <it>speG</it> gene was present. Synteny analyses based on genome-wide comparisons of GAS and SDSE indicated that <it>speG</it> is the direct descendant of a common ancestor of streptococcal SAgs, whereas <it>smez</it> was deleted from SDSE after SDSE and GAS split from a common ancestor. Cumulative nucleotide skew analysis of SDSE genomes suggested that <it>speG</it> was located outside segments of steeper slopes than the stable region in the genome, whereas the region flanking <it>smez</it> was unstable, as expected from the results of GAS. We also detected a previously undescribed staphylococcal SAg gene, <it>selW</it>, and a staphylococcal SAg -like gene, <it>ssl</it>, in the core genomes of all <it>Staphylococcus aureus</it> strains sequenced. Amino acid substitution analyses, based on dN/dS window analysis of the products encoded by <it>speG</it>, <it>selW</it> and <it>ssl</it> suggested that all three genes have been subjected to strong positive selection. Evolutionary analysis based on the Bayesian Markov chain Monte Carlo method showed that each clade included at least one direct descendant.</p> <p>Conclusions</p> <p>Our findings reveal a plausible model for the comprehensive evolutionary pathway of streptococcal and staphylococcal SAgs.</p>