Logo of compfungenJournal's HomeManuscript SubmissionAims and ScopeAuthor GuidelinesEditorial BoardHome
Comp Funct Genomics. 2004 Feb; 5(1): 79–84.
PMCID: PMC2447317

The Evolution of Protein Interaction Networks in Regulatory Proteins


Interactions between proteins are essential for intracellular communication. They form complex networks which have become an important source for functional analysis of proteins. Combining phylogenies with network analysis, we investigate the evolutionary history of interaction networks from the bHLH, NR and bZIP transcription-factor families. The bHLH and NR networks show a hub-like structure with varying γ values. Mutation and gene duplication play an important role in adding and removing interactions. We conclude that in several of the protein families that we have studied, networks have primarily arisen by the development of heterodimerizing transcription factors, from an ancestral gene which interacts with any of the newly emerging proteins but also homodimerizes.

Full Text

The Full Text of this article is available as a PDF (101K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. [PubMed]
  • Apic G, Gough J, Teichmann SA. Domain combinations in archaeal, eubacterial and eukaryotic proteomes. J Mol Biol. 2001 Jul 6;310(2):311–325. [PubMed]
  • Atchley WR, Fitch WM. A natural classification of the basic helix-loop-helix class of transcription factors. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5172–5176. [PMC free article] [PubMed]
  • Bornberg-Bauer E, Rivals E, Vingron M. Computational approaches to identify leucine zippers. Nucleic Acids Res. 1998 Jun 1;26(11):2740–2746. [PMC free article] [PubMed]
  • Brannetti B, Via A, Cestra G, Cesareni G, Helmer-Citterich M. SH3-SPOT: an algorithm to predict preferred ligands to different members of the SH3 gene family. J Mol Biol. 2000 Apr 28;298(2):313–328. [PubMed]
  • Bu Dongbo, Zhao Yi, Cai Lun, Xue Hong, Zhu Xiaopeng, Lu Hongchao, Zhang Jingfen, Sun Shiwei, Ling Lunjiang, Zhang Nan, et al. Topological structure analysis of the protein-protein interaction network in budding yeast. Nucleic Acids Res. 2003 May 1;31(9):2443–2450. [PMC free article] [PubMed]
  • Escriva H, Safi R, Hänni C, Langlois MC, Saumitou-Laprade P, Stehelin D, Capron A, Pierce R, Laudet V. Ligand binding was acquired during evolution of nuclear receptors. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6803–6808. [PMC free article] [PubMed]
  • Ito Takashi, Ota Kazuhisa, Kubota Hiroyuki, Yamaguchi Yoshihiro, Chiba Tomoko, Sakuraba Kazumi, Yoshida Mikio. Roles for the two-hybrid system in exploration of the yeast protein interactome. Mol Cell Proteomics. 2002 Aug;1(8):561–566. [PubMed]
  • Jeong H, Mason SP, Barabási AL, Oltvai ZN. Lethality and centrality in protein networks. Nature. 2001 May 3;411(6833):41–42. [PubMed]
  • Laudet V. Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J Mol Endocrinol. 1997 Dec;19(3):207–226. [PubMed]
  • Ledent V, Vervoort M. The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis. Genome Res. 2001 May;11(5):754–770. [PMC free article] [PubMed]
  • Newman John R S, Keating Amy E. Comprehensive identification of human bZIP interactions with coiled-coil arrays. Science. 2003 Jun 27;300(5628):2097–2101. [PubMed]
  • O'Shea EK, Rutkowski R, Kim PS. Mechanism of specificity in the Fos-Jun oncoprotein heterodimer. Cell. 1992 Feb 21;68(4):699–708. [PubMed]
  • Pastor-Satorras Romualdo, Smith Eric, Solé Ricard V. Evolving protein interaction networks through gene duplication. J Theor Biol. 2003 May 21;222(2):199–210. [PubMed]
  • Rzhetsky A, Gomez SM. Birth of scale-free molecular networks and the number of distinct DNA and protein domains per genome. Bioinformatics. 2001 Oct;17(10):988–996. [PubMed]
  • Salwinski Lukasz, Eisenberg David. Computational methods of analysis of protein-protein interactions. Curr Opin Struct Biol. 2003 Jun;13(3):377–382. [PubMed]
  • Schächter Vincent. Bioinformatics of large-scale protein interaction networks. Biotechniques. 2002 Mar;Suppl:16–27. [PubMed]
  • Schwikowski B, Uetz P, Fields S. A network of protein-protein interactions in yeast. Nat Biotechnol. 2000 Dec;18(12):1257–1261. [PubMed]
  • Vazquez Alexei, Flammini Alessandro, Maritan Amos, Vespignani Alessandro. Global protein function prediction from protein-protein interaction networks. Nat Biotechnol. 2003 Jun;21(6):697–700. [PubMed]
  • Villanueva Josep, Fernández-Ballester Gregorio, Querol Enrique, Aviles Francesc X, Serrano Luis. Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling. J Mol Biol. 2003 Jul 25;330(5):1039–1048. [PubMed]
  • Vinson Charles, Myakishev Max, Acharya Asha, Mir Alain A, Moll Jonathan R, Bonovich Maria. Classification of human B-ZIP proteins based on dimerization properties. Mol Cell Biol. 2002 Sep;22(18):6321–6335. [PMC free article] [PubMed]
  • Wagner Andreas. How the global structure of protein interaction networks evolves. Proc Biol Sci. 2003 Mar 7;270(1514):457–466. [PMC free article] [PubMed]
  • Wiens Matthias, Batel Renato, Korzhev Michael, Müller Werner E G. Retinoid X receptor and retinoic acid response in the marine sponge Suberites domuncula. J Exp Biol. 2003 Sep;206(Pt 18):3261–3271. [PubMed]
  • Wolf Yuri I, Karev Georgy, Koonin Eugene V. Scale-free networks in biology: new insights into the fundamentals of evolution? Bioessays. 2002 Feb;24(2):105–109. [PubMed]
  • Wuchty S. Scale-free behavior in protein domain networks. Mol Biol Evol. 2001 Sep;18(9):1694–1702. [PubMed]

Articles from Comparative and Functional Genomics are provided here courtesy of Hindawi Publishing Corporation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...