title: Origin and evolution of dishevelled.
abstract: Dishevelled (Dsh or Dvl) is an important signaling protein, playing a key role in Wnt signaling and relaying cellular information for several developmental pathways. Dsh is highly conserved among metazoans and has expanded into a multigene family in most bilaterian lineages, including vertebrates, planarians, and nematodes. These orthologs, where explored, are known to have considerable overlap in function, but evidence for functional specialization continues to mount. We performed a comparative analysis of Dsh across animals to explore protein architecture and identify conserved and divergent features that could provide insight into functional specialization with an emphasis on invertebrates, especially nematodes. We find evidence of dynamic evolution of Dsh, particularly among nematodes, with taxa varying in ortholog number from one to three. We identify a new domain specific to some nematode lineages and find an unexpected nuclear localization signal conserved in many Dsh orthologs. Our findings raise questions of protein evolution in general and provide clues as to how animals have dealt with the complex intricacies of having a protein, such as Dsh, act as a central messenger hub connected to many different and vitally important pathways. We discuss our findings in the context of functional specialization and bring many testable hypotheses to light.
authors: Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
authors: Adler R
authors: AR
authors: Dillman
authors: Paul J
authors: PJ
authors: Minor
authors: Paul W
authors: PW
authors: Sternberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D000818:Animals; D002107:Caenorhabditis / Q000378:metabolism; D000072261:Dishevelled Proteins; D019143:Evolution, Molecular; D007448:Invertebrates / Q000378:metabolism; D009348:Nematoda / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010766:Phosphorylation; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D051153:Wnt Proteins
keywords: C. elegans; Nematoda; Wnt; dishevelled; protein evolution
references: J Biol. 2005;4(1):3
references: 15720724
references: Development. 2005 Oct;132(20):4421-36
references: 16192308
references: Cladistics. 1999 Dec;15(4):415-428
references: 34902941
references: Mech Dev. 1999 May;83(1-2):27-37
references: 10507837
references: Genome Res. 2010 Dec;20(12):1740-7
references: 20980554
references: Genome Res. 2003 Sep;13(9):2178-89
references: 12952885
references: Dev Biol. 2011 Dec 1;360(1):132-42
references: 21963539
references: Lab Invest. 2007 Feb;87(2):97-103
references: 17211410
references: Development. 2002 Dec;129(24):5827-38
references: 12421720
references: BMC Dev Biol. 2008 Jun 09;8:63
references: 18541012
references: Nat Rev Genet. 2007 Feb;8(2):126-38
references: 17230199
references: Cell. 1995 Oct 6;83(1):101-10
references: 7553861
references: Cell. 2012 Jul 20;150(2):351-65
references: 22817897
references: Genes Dev. 2010 Oct 1;24(19):2157-68
references: 20837657
references: Syst Biol. 2008 Oct;57(5):758-71
references: 18853362
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D302-5
references: 22053084
references: Curr Biol. 2011 Mar 8;21(5):377-83
references: 21353558
references: Genetics. 2002 Jun;161(2):747-62
references: 12072470
references: PLoS Biol. 2011 Apr;9(4):e1001050
references: 21526226
references: Nat Methods. 2012 Jul 30;9(8):772
references: 22847109
references: Genes Dev. 1994 Jan;8(1):118-30
references: 8288125
references: Dev Cell. 2005 Feb;8(2):167-78
references: 15691759
references: J Cell Biol. 2000 Jun 26;149(7):1433-42
references: 10871283
references: BMC Evol Biol. 2011 Nov 21;11:339
references: 22103856
references: Evol Dev. 2010 Sep-Oct;12(5):494-518
references: 20883218
references: J Morphol. 2007 Aug;268(8):649-63
references: 17514723
references: Science. 1998 Dec 11;282(5396):2041-6
references: 9851921
references: Genetics. 2012 Dec;192(4):1295-313
references: 23023003
references: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2813-8
references: 21282632
references: Cell. 1997 Sep 5;90(5):895-905
references: 9298901
references: Nucleic Acids Res. 2003 Jul 1;31(13):3537-9
references: 12824361
references: Science. 1998 Dec 11;282(5396):2033-41
references: 9851920
references: PLoS Genet. 2010 Aug 12;6(8):
references: 20711352
references: Dev Biol. 2006 May 15;293(2):316-29
references: 16631156
references: Mol Biol Evol. 2011 Oct;28(10):2731-9
references: 21546353
references: Genetics. 2013 Apr;193(4):1279-95
references: 23410827
references: PLoS Genet. 2008 Nov;4(11):e1000259
references: 19008950
references: PLoS One. 2007 Oct 10;2(10):e1031
references: 17925879
references: Cell. 2009 Jul 23;138(2):314-27
references: 19632181
references: Dev Dyn. 2009 Aug;238(8):2044-57
references: 19618470
references: Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):E812-20
references: 22411803
references: Syst Biol. 2003 Oct;52(5):696-704
references: 14530136
references: J Comp Neurol. 2009 Dec 10;517(5):616-32
references: 19824103
references: Dev Biol. 2009 Apr 15;328(2):245-56
references: 19389360
references: Cladistics. 1999 Dec;15(4):407-414
references: 34902938
references: Dev Biol. 2003 Jan 1;253(1):1-17
references: 12490194
references: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8038-43
references: 18524955
references: Cell Signal. 2010 May;22(5):717-27
references: 20006983
references: PLoS Genet. 2012;8(7):e1002764
references: 22807683
references: Genome Res. 2009 Mar;19(3):470-80
references: 19204328
references: Science. 1998 Dec 11;282(5396):2012-8
references: 9851916
references: Genes Dev. 1996 Sep 1;10(17):2189-97
references: 8804313
references: BMC Bioinformatics. 2004 Aug 19;5:113
references: 15318951
references: Nature. 2005 Jan 13;433(7022):156-60
references: 15650739
references: Annu Rev Genet. 2008;42:517-40
references: 18710302
references: J Comp Neurol. 2009 Jan 10;512(2):271-81
references: 19003904
references: Science. 2008 Jan 18;319(5861):323-7
references: 18063757
references: Cold Spring Harb Perspect Biol. 2012 Jul 01;4(7):a007922
references: 22751150
references: Nature. 1998 Mar 5;392(6671):71-5
references: 9510248
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8112-5
references: 12060757
references: Mol Biol Evol. 2006 Sep;23(9):1792-800
references: 16790472
references: J Nematol. 2012 Jun;44(2):191-205
references: 23482088
references: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):254-9
references: 21173231
references: Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):606-11
references: 9435239