title: Membrane porters of ATP-binding cassette transport systems are polyphyletic.
abstract: The ATP-binding cassette (ABC) superfamily consists of both importers and exporters. These transporters have, by tradition, been classified according to the ATP hydrolyzing constituents, which are monophyletic. The evolutionary origins of the transmembrane porter proteins/domains are not known. Using five distinct computer programs, we here provide convincing statistical data suggesting that the transmembrane domains of ABC exporters are polyphyletic, having arisen at least three times independently. ABC1 porters arose by intragenic triplication of a primordial two-transmembrane segment (TMS)-encoding genetic element, yielding six TMS proteins. ABC2 porters arose by intragenic duplication of a dissimilar primordial three-TMS-encoding genetic element, yielding a distinctive protein family, nonhomologous to the ABC1 proteins. ABC3 porters arose by duplication of a primordial four-TMS-encoding genetic element, yielding either eight- or 10-TMS proteins. We assign each of 48 of the 50 currently recognized families of ABC exporters to one of the three evolutionarily distinct ABC types. Currently available high-resolution structural data for ABC porters are fully consistent with our findings. These results provide guides for future structural and mechanistic studies of these important transport systems.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Maxim
authors.initials: M
authors.lastname: Dukarevich
authors.forename: Eric I
authors.initials: EI
authors.lastname: Sun
authors.forename: Ming Ren
authors.initials: MR
authors.lastname: Yen
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000145:classification / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D001692:Biological Transport / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D008565:Membrane Proteins