Schematic diagram of the molecular evolution of streptococcal SAgs, SEs and SSLs. This model was based on the results of this study. S. aureus and Streptococcus are shown in blue and orange, respectively, with the two lineages of SAgs consisting of those derived from these two species. The first step of SAg diversification consisted of the mobilization of ancestral SAgs (ancestral selW and ssl-like genes in S. aureus, and speG and smez in Streptococcus) by mobile elements. During their repeated transfer among bacteria, genes that might have been incorporated into mobile elements diversified, were transferred to Streptococcus and became ancestral to streptococcal SAgs, similar to S. aureus SAgs such as speA and ssa. In streptococcal lineages, the ancestral bacterium of GAS and SDSE harbored ancestral speG and smez. After speciation of GAS and SDSE, smez was lost from the SDSE lineage during massive genome rearrangements, whereas speG in SDSE was inherited from ancestral GAS and SDSE. In the GAS lineage, horizontal transfer of SAgs by streptococcal phages was linked to their diversification.