A Novel Translational Reprogramming of the Insertion Sequence IS1239 by 1-bp Deletion Resulted in Polymorphism of C-Terminal Amino Acid Sequences in the Pathogenic Bacterium Streptococcus pyogenes.

The insertion sequence family IS1239 has been found to mediate multiple asymmetric rearrangements in the pathogenic bacterium, Group A Streptococcus pyogenes (GAS), but not symmetric rearrangements as observed commonly in other bacteria. Sequence characterizations showed that the copies of IS1239 in GAS encode variable C-termini by utilizing flanking sequences downstream the insertion sites. We found that the variability of the C-termini was caused by translational reprogramming from a 1-bp frame-shift deletion at the 3'-terminus of the gene. The translational reprogramming results in extension and polymorphism of the C-terminal sequences, which was only observed in GAS. Selection analyses indicated that the C-terminal region of IS1239 proteins in GAS is under relaxed selection constraints, thus allowing more sequence changes in this region without affecting the transposition activity of this enzyme. We also showed that the insertion of IS1239 and the formation of flexible C-termini exhibit signatures related to evolutionary selection based on three lines of evidence: (i) copies of IS1239 in GAS were inserted in conserved genomic regions compared to those from Streptococcus pneumoniae; (ii) copies of IS1239 in GAS are more frequently inserted in the neighboring regions of tRNAs, rRNAs, or ribosomal proteins, but rarely interrupt their normal coding; (iii) the sites predicted to be under relaxed selective constraints in GAS lineage are enriched in regions outside the functional domains and near the 1-bp deletion which induced the polymorphism of C-termini of IS1239 in GAS.