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Evolutionary conservation of motif constituents in the yeast protein interaction network


Understanding why some cellular components are conserved across species but others evolve rapidly is a key question of modern biology1,2,3. Here we show that in Saccharomyces cerevisiae, proteins organized in cohesive patterns of interactions are conserved to a substantially higher degree than those that do not participate in such motifs. We find that the conservation of proteins in distinct topological motifs correlates with the interconnectedness and function of that motif and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate.

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Figure 1: Relationship between the topology of a protein interaction network and the evolutionary conservation of individual proteins.


  1. 1

    Hasty, J., McMillen, D. & Collins, J.J. Engineered gene circuits. Nature 420, 224–230 (2002).

    CAS  Article  Google Scholar 

  2. 2

    Kitano, H. Systems biology: a brief overview. Science 295, 1662–1664 (2002).

    CAS  Article  Google Scholar 

  3. 3

    Rao, C.V., Wolf, D.M. & Arkin, A.P. Control, exploitation and tolerance of intracellular noise. Nature 420, 231–237 (2002).

    CAS  Article  Google Scholar 

  4. 4

    Hartwell, L.H., Hopfield, J.J., Leibler, S. & Murray, A.W. From molecular to modular cell biology. Nature 402, C47–C52 (1999).

    CAS  Article  Google Scholar 

  5. 5

    Oltvai, Z.N. & Barabási, A.-L. Life's complexity pyramid. Science 298, 763–764 (2002).

    CAS  Article  Google Scholar 

  6. 6

    Shen-Orr, S.S., Milo, R., Mangan, S. & Alon, U. Network motifs in the transcriptional regulation network of Escherichia coli. Nat. Genet. 31, 64–68 (2002).

    CAS  Article  Google Scholar 

  7. 7

    Milo, R., Shen-Orr, S.S., Itzkovitz, S., Kashtan, N. & Alon, U. Network motifs: simple building blocks of complex networks. Science 298, 824–827 (2002).

    CAS  Article  Google Scholar 

  8. 8

    Lee, T.I. et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804 (2002).

    CAS  Article  Google Scholar 

  9. 9

    Xenarios, I. et al. DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res. 30, 303–305 (2002).

    CAS  Article  Google Scholar 

  10. 10

    Von Mering, C. et al. Comparative assessment of large-scale data sets of protein protein interactions. Nature 417, 399–403 (2002).

    CAS  Article  Google Scholar 

  11. 11

    Remm, M., Storm, C.E.V. & Sonnhammer, E.L. Automatic clustering of orthologs and in-paralogs from pairwise species comparisons. J. Mol. Biol. 314, 1041–1052 (2001).

    CAS  Article  Google Scholar 

  12. 12

    Watts, D.J. & Strogatz, S.H. Collective dynamics of 'small-world' networks. Nature 393, 440–442 (1998).

    CAS  Article  Google Scholar 

  13. 13

    Ravasz, E., Somera, A.L., Mongru, D.A., Oltvai, Z.N. & Barabási, A.-L. Hierarchical organization of modularity in metabolic networks. Science 297, 1551–1555 (2002).

    CAS  Article  Google Scholar 

  14. 14

    Rives, A.W. & Galitski, T. Modular organization of cellular networks. Proc. Natl. Acad. Sci. USA 100, 1128–1133 (2003).

    CAS  Article  Google Scholar 

  15. 15

    Mewes, H.W. et al. MIPS: a database for genomes and protein sequences. Nucleic Acids Res. 30, 31–34 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Hurst, L.D. & Smith, N.G. Do essential genes evolve slowly? Curr. Biol. 9, 747–750 (1999).

    CAS  Article  Google Scholar 

  17. 17

    Hirsh, A.E. & Fraser, H.B. Protein dispensability and rate of evolution. Nature 411, 1046–1049 (2001).

    CAS  Article  Google Scholar 

  18. 18

    Hirsh, A.E. & Fraser, H.B. Genomic function (communication arising): rate of evolution and gene dispensability. Nature 421, 497–498 (2003).

    CAS  Article  Google Scholar 

  19. 19

    Fraser, H.B., Hirsh, A.E., Steinmetz, L.M., Scharfe, C. & Feldman, M.W. Evolutionary rate in the protein interaction network. Science 296, 750–752 (2002).

    CAS  Article  Google Scholar 

  20. 20

    Pal, C., Papp, B. & Hurst, L.D. Genomic function (communication arising): rate of evolution and gene dispensability. Nature 421, 496–497 (2003).

    CAS  Article  Google Scholar 

  21. 21

    Jordan, I.K., Rogozin, I.B., Wolf, Y.I. & Koonin, E.V. Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res. 12, 962–968 (2002).

    CAS  Article  Google Scholar 

  22. 22

    Snel, B., Bork, P. & Huynen, M.A. The identification of functional modules from the genomic association of genes. Proc. Natl. Acad. Sci. USA 99, 5890–5895 (2002).

    CAS  Article  Google Scholar 

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Research at the University of Notre Dame and Northwestern University was supported by grants from the US National Institutes of Health (National Institute of General Medical Sciences) and the Department of Energy Genomes to Life Program. Research at the University of Notre Dame was also supported by the National Science Foundation.

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Correspondence to Z N Oltvai or A-L Barabási.

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The authors declare no competing financial interests.

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Wuchty, S., Oltvai, Z. & Barabási, AL. Evolutionary conservation of motif constituents in the yeast protein interaction network. Nat Genet 35, 176–179 (2003).

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