Figure 3.

A hypothetical scenario for the origin and dissemination of the rhomboid family proteases. The figure schematically shows the proposed three stages of evolution of the rhomboid family: I - the progenitor of the rhomboid family functions as a transporter for a regulatory peptide in some bacterial lineage. II - the catalytic site of the intramembrane protease evolves allowing the switch to RIP as the mechanism of the regulatory peptide release. III - the emergence of RIP is followed by a burst of HGT. R, regulatory peptide; the transmembrane helices of rhomboid are designated as in Fig. 1, their topology in the membrane is based on that proposed in Ref. 7; the catalytic histidine and serine are shown and connected by a dotted line to indicate the proposed charge-relay system of the protease; possible ancillary catalytic residues are not shown.