The rhomboids: a near ubiquitous family of intramembrane serine proteases evolved via multiple horizontal gene transfers

BACKGROUND: The rhomboid family consists of polytopic membrane proteins, which show a level of evolutionary conservation that is unique among membrane proteins. The rhomboids are present in nearly all sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator Rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes. RESULTS: Phylogenetic tree analysis suggests that, despite the broad distribution in all three kingdoms of life, the rhomboid family was not present in the last universal common ancestor of the extant life forms, but instead evolved in bacteria and has been acquired by archaea and eukaryotes via several independent horizontal gene transfer events. In eukaryotes, two distinct, ancient horizontal acquisitions apparently gave rise to the two major subfamilies typified by Rhomboid and PARL (presenilin-associated Rhomboid-like protein), respectively. The subsequent evolution of the rhomboid family in eukaryotes proceeded via multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity. CONCLUSIONS: Although the near universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates bacterial origin with subsequent dissemination via horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario of origin of intracellular membrane proteases from membrane transporters is proposed.