title: Evolutionary relationships of ATP-Binding Cassette (ABC) uptake porters.
abstract: BACKGROUND
  The ATP-Binding Cassette (ABC) functional superfamily includes integral transmembrane exporters that have evolved three times independently, forming three families termed ABC1, ABC2 and ABC3, upon which monophyletic ATPases have been superimposed for energy-coupling purposes [e.g., J Membr Biol 231(1):1-10, 2009]. The goal of the work reported in this communication was to understand how the integral membrane constituents of ABC uptake transporters with different numbers of predicted or established transmembrane segments (TMSs) evolved. In a few cases, high resolution 3-dimensional structures were available, and in these cases, their structures plus primary sequence analyses allowed us to predict evolutionary pathways of origin.
  
  
  RESULTS
  All of the 35 currently recognized families of ABC uptake proteins except for one (family 21) were shown to be homologous using quantitative statistical methods. These methods involved using established programs that compare native protein sequences with each other, after having compared each sequence with thousands of its own shuffled sequences, to gain evidence for homology. Topological analyses suggested that these porters contain numbers of TMSs ranging from four or five to twenty. Intragenic duplication events occurred multiple times during the evolution of these porters. They originated from a simple primordial protein containing 3 TMSs which duplicated to 6 TMSs, and then produced porters of the various topologies via insertions, deletions and further duplications. Except for family 21 which proved to be related to ABC1 exporters, they are all related to members of the previously identified ABC2 exporter family. Duplications that occurred in addition to the primordial 3 → 6 duplication included 5 → 10, 6 → 12 and 10 → 20 TMSs. In one case, protein topologies were uncertain as different programs gave discrepant predictions. It could not be concluded with certainty whether a 4 TMS ancestral protein or a 5 TMS ancestral protein duplicated to give an 8 or a 10 TMS protein. Evidence is presented suggesting but not proving that the 2TMS repeat unit in ABC1 porters derived from the two central TMSs of ABC2 porters. These results provide structural information and plausible evolutionary pathways for the appearance of most integral membrane constituents of ABC uptake transport systems.
  
  
  CONCLUSIONS
  Almost all integral membrane uptake porters of the ABC superfamily belong to the ABC2 family, previously established for exporters. Most of these proteins can have 5, 6, 10, 12 or 20 TMSs per polypeptide chain. Evolutionary pathways for their appearance are proposed.
authors: Department of Molecular Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors: Wei Hao
authors: WH
authors: Zheng
authors: Åke
authors: Å
authors: Västermark
authors: Maksim A
authors: MA
authors: Shlykov
authors: Vamsee
authors: V
authors: Reddy
authors: Eric I
authors: EI
authors: Sun
authors: Milton H
authors: MH
authors: Saier
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D018528:ATP-Binding Cassette Transporters
references: Bioinformatics. 2006 Jul 1;22(13):1658-9
references: 16731699
references: Bioinformatics. 2007 Nov 1;23(21):2947-8
references: 17846036
references: J Bacteriol. 1992 Apr;174(7):2305-11
references: 1551849
references: EMBO J. 2003 Nov 17;22(22):5983-93
references: 14609945
references: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D181-6
references: 16381841
references: Res Microbiol. 2005 Mar;156(2):270-7
references: 15748994
references: J Mol Microbiol Biotechnol. 2009;17(4):163-76
references: 19776645
references: Science. 1981 Oct 9;214(4517):149-59
references: 7280687
references: J Mol Microbiol Biotechnol. 2006;11(6):345-60
references: 17114898
references: Science. 2008 Jul 11;321(5886):246-50
references: 18511655
references: J Mol Microbiol Biotechnol. 2002 Jul;4(4):375-7
references: 12125818
references: J Mol Biol. 2001 Jan 19;305(3):567-80
references: 11152613
references: Methods Mol Biol. 2010;637:47-64
references: 20419429
references: J Membr Biol. 2009 Sep;231(1):1-10
references: 19806386
references: Methods Enzymol. 1983;91:524-45
references: 6855599
references: BMC Evol Biol. 2004 Sep 17;4:33
references: 15377393
references: Mol Microbiol. 2003 Jun;48(5):1145-56
references: 12787345
references: J Mol Microbiol Biotechnol. 2001 Apr;3(2):285-6
references: 11321584
references: Microbiology (Reading). 2004 Jan;150(Pt 1):1-3
references: 14702390
references: Science. 2007 Jan 19;315(5810):373-7
references: 17158291
references: FEBS J. 2012 Jun;279(11):2036-46
references: 22568782
references: FEMS Microbiol Rev. 2011 Jan;35(1):3-67
references: 20497229
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W465-8
references: 19429891
references: Bioinformatics. 2001 Sep;17(9):849-50
references: 11590105
references: Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95
references: 6546423
references: Science. 2008 Jul 11;321(5886):250-3
references: 18621668
references: J Membr Biol. 2011 Mar;240(2):89-110
references: 21347612
references: J Mol Microbiol Biotechnol. 2001 Oct;3(4):501-2
references: 11545267
references: J Mol Microbiol Biotechnol. 2003;5(1):1-6
references: 12673055
references: J Mol Evol. 1999 Jan;48(1):22-41
references: 9873074
references: J Membr Biol. 2009 Jun;229(3):115-30
references: 19548020
references: Crit Rev Biochem Mol Biol. 2002;37(5):287-337
references: 12449427
references: J Bacteriol. 2009 Jan;191(1):42-51
references: 18931129
references: J Mol Microbiol Biotechnol. 1999 Nov;1(2):281-7
references: 10943557
references: J Biol Chem. 2009 Apr 10;284(15):9637-41
references: 19074771
references: Microbiol Rev. 1994 Mar;58(1):71-93
references: 8177172
references: Microbiol Rev. 1993 Jun;57(2):320-46
references: 8336670
references: Nature. 2007 Nov 22;450(7169):515-21
references: 18033289
references: Science. 2007 Sep 7;317(5843):1387-90
references: 17673622