title: Protein evolution in yeast transcription factor subnetworks.
abstract: When averaged over the full yeast protein-protein interaction and transcriptional regulatory networks, protein hubs with many interaction partners or regulators tend to evolve significantly more slowly due to increased negative selection. However, genome-wide analysis of protein evolution in the subnetworks of associations involving yeast transcription factors (TFs) reveals that TF hubs do not tend to evolve significantly more slowly than TF non-hubs. This result holds for all four major types of TF hubs: interaction hubs, regulatory in-degree and out-degree hubs, as well as co-regulatory hubs that jointly regulate target genes with many TFs. Furthermore, TF regulatory in-degree hubs tend to evolve significantly more quickly than TF non-hubs. Most importantly, the correlations between evolutionary rate (K(A)/K(S)) and degrees for TFs are significantly more positive than those for generic proteins within the same global protein-protein interaction and transcriptional regulatory networks. Compared to generic protein hubs, TF hubs operate at a higher level in the hierarchical structure of cellular networks, and hence experience additional evolutionary forces (relaxed negative selection or positive selection through network rewiring). The striking difference between the evolution of TF hubs and generic protein hubs demonstrates that components within the same global network can be governed by distinct organizational and evolutionary principles.
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Eric A
authors.initials: EA
authors.lastname: Franzosa
authors.forename: Xiang-Sun
authors.initials: XS
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
mesh_terms: D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D025941:Protein Interaction Mapping; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
references.citation: Science. 2007 Aug 10;317(5839):815-9
references.pmid: 17690298
references.citation: Science. 2005 Feb 4;307(5710):724-7
references.pmid: 15692050
references.citation: Mol Biol Evol. 2007 May;24(5):1113-21
references.pmid: 17347158
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14338-43
references.pmid: 16176987
references.citation: PLoS Biol. 2004 Dec;2(12):e398
references.pmid: 15534694
references.citation: Mol Biol Evol. 2004 Jan;21(1):108-16
references.pmid: 14595100
references.citation: BMC Evol Biol. 2007 Jan 29;7:9
references.pmid: 17257443
references.citation: Genome Biol. 2005;6(12):R103
references.pmid: 16356266
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5483-8
references.pmid: 15800036
references.citation: Genome Biol. 2009;10(4):R35
references.pmid: 19358738
references.citation: Science. 2002 Oct 25;298(5594):799-804
references.pmid: 12399584
references.citation: Science. 2006 Dec 22;314(5807):1938-41
references.pmid: 17185604
references.citation: Nucleic Acids Res. 1998 Jan 1;26(1):73-9
references.pmid: 9399804
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D446-51
references.pmid: 16381908
references.citation: Science. 2008 Mar 28;319(5871):1797-9
references.pmid: 18369141
references.citation: Science. 2000 Nov 10;290(5494):1151-5
references.pmid: 11073452
references.citation: Mol Biol Evol. 2000 Jan;17(1):32-43
references.pmid: 10666704
references.citation: Nature. 2004 Sep 16;431(7006):308-12
references.pmid: 15372033
references.citation: Science. 2009 Jan 23;323(5913):498-501
references.pmid: 19164747
references.citation: Nucleic Acids Res. 1987 Feb 11;15(3):1281-95
references.pmid: 3547335
references.citation: Cell. 2008 Jun 27;133(7):1135-7
references.pmid: 18585345
references.citation: Nat Rev Genet. 2004 Feb;5(2):101-13
references.pmid: 14735121
references.citation: Mol Biol Evol. 2009 Oct;26(10):2387-95
references.pmid: 19597162
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13532-7
references.pmid: 16157877
references.citation: BMC Evol Biol. 2004 May 27;4:13
references.pmid: 15165289
references.citation: Nucleic Acids Res. 2009 Oct;37(18):5943-58
references.pmid: 19661283
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9
references.pmid: 16381927
references.citation: BMC Evol Biol. 2003 May 23;3:11
references.pmid: 12769820
references.citation: Mol Biol Evol. 2006 Feb;23(2):327-37
references.pmid: 16237209
references.citation: Genome Biol. 2004;5(2):206
references.pmid: 14759249
references.citation: Nature. 2004 Jun 10;429(6992):661-4
references.pmid: 15190353
references.citation: BMC Evol Biol. 2003 Jan 6;3:1
references.pmid: 12515583
references.citation: Nature. 2006 Sep 28;443(7110):415-20
references.pmid: 17006507
references.citation: BMC Evol Biol. 2003 Oct 02;3:21
references.pmid: 14525624
references.citation: J Evol Biol. 2009 Dec;22(12):2430-7
references.pmid: 19878412
references.citation: Science. 2002 Apr 26;296(5568):750-2
references.pmid: 11976460
references.citation: Science. 2005 Aug 5;309(5736):938-40
references.pmid: 16081737
references.citation: Cell. 2003 Nov 14;115(4):389-99
references.pmid: 14622594
references.citation: Mol Biol Evol. 2006 Sep;23(9):1751-61
references.pmid: 16782762
references.citation: Science. 2006 May 19;312(5776):1054-9
references.pmid: 16709784
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17614-9
references.pmid: 17101967
references.citation: Curr Opin Struct Biol. 2004 Jun;14(3):283-91
references.pmid: 15193307
references.citation: Genes Dev. 2006 Feb 15;20(4):435-48
references.pmid: 16449570
references.citation: BMC Evol Biol. 2004 Jun 01;4:14
references.pmid: 15171796
references.citation: Comput Appl Biosci. 1997 Oct;13(5):555-6
references.pmid: 9367129
references.citation: PLoS Comput Biol. 2009 Jun;5(6):e1000413
references.pmid: 19521505
references.citation: Nature. 2007 Sep 6;449(7158):54-61
references.pmid: 17805289
references.citation: Nature. 2004 Jul 1;430(6995):88-93
references.pmid: 15190252
references.citation: Genetics. 2001 Jun;158(2):927-31
references.pmid: 11430355
references.citation: Curr Biol. 2007 Jun 19;17(12):1007-13
references.pmid: 17540568
references.citation: Nature. 2008 Apr 17;452(7189):840-5
references.pmid: 18421347
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Nature. 2001 Jun 28;411(6841):1046-9
references.pmid: 11429604
references.citation: J Exp Zool B Mol Dev Evol. 2004 Jul 15;302(4):392-411
references.pmid: 15287103
references.citation: Curr Opin Biotechnol. 2006 Oct;17(5):481-7
references.pmid: 16962765
references.citation: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7203-8
references.pmid: 15883364
references.citation: Nature. 2006 Sep 28;443(7110):401-2
references.pmid: 17006502
references.citation: Mol Cell. 2008 Mar 14;29(5):552-62
references.pmid: 18342603
references.citation: Nat Rev Genet. 2006 May;7(5):337-48
references.pmid: 16619049
references.citation: Nature. 2004 Sep 2;431(7004):99-104
references.pmid: 15343339
references.citation: PLoS Biol. 2008 Feb;6(2):e38
references.pmid: 18303948
references.citation: Genes Dev. 2002 Dec 1;16(23):3017-33
references.pmid: 12464632