title: Internal duplications in α-helical membrane protein topologies are common but the nonduplicated forms are rare.
abstract: Many α-helical membrane proteins contain internal symmetries, indicating that they might have evolved through a gene duplication and fusion event. Here, we have characterized internal duplications among membrane proteins of known structure and in three complete genomes. We found that the majority of large transmembrane (TM) proteins contain an internal duplication. The duplications found showed a large variability both in the number of TM-segments included and in their orientation. Surprisingly, an approximately equal number of antiparallel duplications and parallel duplications were found. However, of all 11 superfamilies with an internal duplication, only for one, the AcrB Multidrug Efflux Pump, the duplicated unit could be found in its nonduplicated form. An evolutionary analysis of the AcrB homologs indicates that several independent fusions have occurred, including the fusion of the SecD and SecF proteins into the 12-TM-protein SecDF in Brucella and Staphylococcus aureus. In one additional case, the Vitamin B12 transporter-like ABC transporters, the protein had undergone an additional fusion to form protein with 20 TM-helices in several bacterial genomes. Finally, homologs to all human membrane proteins were used to detect the presence of duplicated and nonduplicated proteins. This confirmed that only in rare cases can homologs with different duplication status be found, although internal symmetry is frequent among these proteins. One possible explanation is that it is frequent that duplication and fusion events happen simultaneously and that there is almost always a strong selective advantage for the fused form.
authors.affiliation: CBR,DBB,SBC, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Aron
authors.initials: A
authors.lastname: Hennerdal
authors.forename: Jenny
authors.initials: J
authors.lastname: Falk
authors.forename: Erik
authors.initials: E
authors.lastname: Lindahl
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
mesh_terms: D002002:Brucella / Q000378:metabolism; D019295:Computational Biology; D019143:Evolution, Molecular; D020440:Gene Duplication / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000378:metabolism
chemical_list: D008565:Membrane Proteins