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Network motifs: theory and experimental approaches

Key Points

  • Transcription regulation networks seem to be built of a few regulatory patterns called network motifs.

  • Each network motif can carry out defined information-processing functions. These functions have been experimentally studied in selected systems, mostly Escherichia coli.

  • Negative autoregulation can speed up responses and reduce fluctuations, whereas positive autoregulation slows responses and increases variations.

  • Coherent feedforward loops can show persistence detection, whereas incoherent feedforward loops show pulse generation and response acceleration.

  • Single-input modules can generate temporal programmes of expression.

  • Dense overlapping regulons can act as arrays of gates for combinatorial decision making.

  • Developmental networks display these network motifs, and additional motifs, such as two-point positive-feedforward loops for decision making and memory, and cascades for regulating slow multi-step processes.

  • Network motifs in systems that have been studied experimentally so far seem to be wired together in a 'modular' way that allows us to understand the dynamics of each individual motif, even when it is connected to the rest of the network.

  • Evolution seems to have converged on the same motifs in different systems and different organisms, suggesting that they are selected for again and again on the basis of their biological functions.

  • Other biological networks, such as signalling and neuronal networks, also show network motifs, some of which are similar to the motifs that are found in transcription networks.

Abstract

Transcription regulation networks control the expression of genes. The transcription networks of well-studied microorganisms appear to be made up of a small set of recurring regulation patterns, called network motifs. The same network motifs have recently been found in diverse organisms from bacteria to humans, suggesting that they serve as basic building blocks of transcription networks. Here I review network motifs and their functions, with an emphasis on experimental studies. Network motifs in other biological networks are also mentioned, including signalling and neuronal networks.

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Figure 1: Simple regulation and autoregulation.
Figure 2: Feedforward loops (FFLs).
Figure 3: The coherent type-1 feedforward loop (C1-FFL) and its dynamics.
Figure 4: The incoherent type-1 feeforward loop (I1-FFL) and its dynamics.
Figure 5: The single-input module (SIM) network motif and its dynamics.
Figure 6: The dense overlapping regulon (DOR) network motif.
Figure 7: Network motifs in developmental transcription networks.

References

  1. Alon, U. Introduction to Systems Biology: Design Principles Of Biological Circuits (CRC, Boca Raton, 2006).

    Google Scholar 

  2. Davidson, E. H. The Regulatory Genome: Gene Regulatory Networks In Development And Evolution, (Academic, Burlington, 2006).

    Google Scholar 

  3. Ptashne, M. & Gann, A. Genes & Signals (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2002).

    Google Scholar 

  4. Levine, M. & Davidson, E. H. Gene regulatory networks for development. Proc. Natl Acad. Sci. USA 102, 4936–4942 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thieffry, D., Huerta, A. M., Perez-Rueda, E. & Collado-Vides, J. From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli. Bioessays 20, 433–440 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Milo, R. et al. Network motifs: simple building blocks of complex networks. Science 298, 824–827 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Eichenberger, P. et al. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis. PLoS Biol. 2, e328 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mangan, S., Zaslaver, A. & Alon, U. The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J. Mol. Biol. 334, 197–204 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Odom, D. T. et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378–1381 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Saddic, L. A. et al. The LEAFY target LMI1 is a meristem identity regulator and acts together with LEAFY to regulate expression of CAULIFLOWER. Development 133, 1673–1682 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Swiers, G., Patient, R. & Loose, M. Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification. Dev. Biol. 294, 525–540 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Iranfar, N., Fuller, D. & Loomis, W. F. Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC. Dev. Biol. 290, 460–469 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Milo, R. et al. Superfamilies of designed and evolved networks. Science 303, 1538–1542 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Rosenfeld, N., Elowitz, M. B. & Alon, U. Negative autoregulation speeds the response times of transcription networks. J. Mol. Biol. 323, 785–793 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Savageau, M. A. Comparison of classical and autogenous systems of regulation in inducible operons. Nature 252, 546–549 (1974).

    Article  CAS  PubMed  Google Scholar 

  19. Becskei, A. & Serrano, L. Engineering stability in gene networks by autoregulation. Nature 405, 590–593 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Camas, F. M., Blazquez, J. & Poyatos, J. F. Autogenous and nonautogenous control of response in a genetic network. Proc. Natl Acad. Sci. USA 103, 12718–12723 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zaslaver, A. et al. A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nature Methods 3, 623–628 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Kaern, M., Elston, T. C., Blake, W. J. & Collins, J. J. Stochasticity in gene expression: from theories to phenotypes. Nature Rev. Genet. 6, 451–464 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Dublanche, Y., Michalodimitrakis, K., Kummerer, N., Foglierini, M. & Serrano, L. Noise in transcription negative feedback loops: simulation and experimental analysis. Mol. Syst. Biol. 2, 41 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kalir, S., Mangan, S. & Alon, U. The coherent feed-forward loop with a SUM input function prolongs flagella production in Escherichia coli. Mol. Syst. Biol. 1, 2005.0006 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maeda, Y. T. & Sano, M. Regulatory dynamics of synthetic gene networks with positive feedback. J. Mol. Biol. 359, 1107–1124 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Becskei, A., Seraphin, B. & Serrano, L. Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J. 20, 2528–2535 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kramer, B. P. & Fussenegger, M. Hysteresis in a synthetic mammalian gene network. Proc. Natl Acad. Sci. USA 102, 9517–9522 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wolf, D. M. & Arkin, A. P. Motifs, modules and games in bacteria. Curr. Opin. Microbiol. 6, 125–134 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Yuh, C. H., Bolouri, H. & Davidson, E. H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science 279, 1896–1902 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Buchler, N. E., Gerland, U. & Hwa, T. On schemes of combinatorial transcription logic. Proc. Natl Acad. Sci. USA 100, 5136–5141 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kalir, S. & Alon, U. Using a quantitative blueprint to reprogram the dynamics of the flagella gene network. Cell 117, 713–720 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Setty, Y., Mayo, A. E., Surette, M. G. & Alon, U. Detailed map of a cis-regulatory input function. Proc. Natl Acad. Sci. USA 100, 7702–7707 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ma, H. W. et al. An extended regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic A cids Res. 32, 6643–6649 (2004).

    Article  CAS  Google Scholar 

  34. Mangan, S. & Alon, U. Structure and function of the feed-forward loop network motif. Proc. Natl Acad. Sci. USA 100, 11980–11985 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Basu, S., Mehreja, R., Thiberge, S., Chen, M. T. & Weiss, R. Spatiotemporal control of gene expression with pulse-generating networks. Proc. Natl Acad. Sci. USA 101, 6355–6360 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mangan, S., Zaslaver, A. & Alon, U. The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli. J. Mol. Biol. 356, 1073–1081 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Hornstein, E. & Shomron, N. Canalization of development by microRNAs. Nature Genet. 38, S20–S24 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V. & Mendell, J. T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839–843 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Johnston, R. J. Jr. et al. An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans. Development 133, 3317–3328 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Ghosh, B., Karmakar, R. & Bose, I. Noise characteristics of feed forward loops. Phys. Biol. 2, 36–45 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Wall, M. E., Dunlop, M. J. & Hlavacek, W. S. Multiple functions of a feed-forward-loop gene circuit. J. Mol. Biol. 349, 501–514 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Hayot, F. & Jayaprakash, C. A feedforward loop motif in transcriptional regulation: induction and repression. J. Theor. Biol. 234, 133–143 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Ishihara, S., Fujimoto, K. & Shibata, T. Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripes. Genes Cells 10, 1025–1038 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Topological generalizations of network motifs. Phys. Rev. E 70, 031909 (2004).

    Article  CAS  Google Scholar 

  45. Dobrin, R., Beg, Q. K., Barabasi, A. L. & Oltvai, Z. N. Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network. BMC Bioinformatics 5, 10 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ronen, M., Rosenberg, R., Shraiman, B. I. & Alon, U. Assigning numbers to the arrows: parameterizing a gene regulation network by using accurate expression kinetics. Proc. Natl Acad. Sci. USA 99, 10555–10560 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zaslaver, A. et al. Just-in-time transcription program in metabolic pathways. Nature Genet. 36, 486–491 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Kalir, S. et al. Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science 292, 2080–2083 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Laub, M. T., McAdams, H. H., Feldblyum, T., Fraser, C. M. & Shapiro, L. Global analysis of the genetic network controlling a bacterial cell cycle. Science 290, 2144–2148 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. McAdams, H. H. & Shapiro, L. A bacterial cell-cycle regulatory network operating in time and space. Science 301, 1874–1877 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Spellman, P. T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273–3297 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ingram, P. J., Stumpf, M. P., Stark, J. Network motifs: structure does not determine function. BMC Genomics 5, 108 (2006).

    Article  CAS  Google Scholar 

  53. Pilpel, Y., Sudarsanam, P. & Church, G. M. Identifying regulatory networks by combinatorial analysis of promoter elements. Nature Genet. 29, 153–159 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Beer, M. & Tavazoie, S. Predicting gene expression from sequence. Cell 117, 185–198 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Rosenfeld, N. & Alon, U. Response delays and the structure of transcription networks. J. Mol. Biol. 329, 645–654 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Babu, M. M., Luscombe, N. M., Aravind, L., Gerstein, M. & Teichmann, S. A. Structure and evolution of transcriptional regulatory networks. Curr. Opin. Struct. Biol. 14, 283–291 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Yu, H., Luscombe, N. M., Qian, J. & Gerstein, M. Genomic analysis of gene expression relationships in transcriptional regulatory networks. Trends Genet. 19, 422–427 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Luscombe, N. M. et al. Genomic analysis of regulatory network dynamics reveals large topological changes. Nature 431, 308–312 (2004).

    Article  CAS  PubMed  Google Scholar 

  59. Amit, I. et al. A module of negative feedback regulators defines growth factor signaling. Nature Genet. 39, 503–512 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Davidson, E. H. et al. A genomic regulatory network for development. Science 295, 1669–1678 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Longabaugh, W. J., Davidson, E. H. & Bolouri, H. Computational representation of developmental genetic regulatory networks. Dev. Biol. 283, 1–16 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Johnston, R. J. Jr, Chang, S., Etchberger, J. F., Ortiz, C. O. & Hobert, O. MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl Acad. Sci. USA 102, 12449–12454 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Xiong, W. & Ferrell, J. E. Jr. A positive-feedback-based bistable 'memory module' that governs a cell fate decision. Nature 426, 460–465 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. Brandman, O., Ferrell, J. E. Jr, Li, R. & Meyer, T. Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science 310, 496–498 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Bolouri, H. & Davidson, E. H. Transcriptional regulatory cascades in development: initial rates, not steady state, determine network kinetics. Proc. Natl Acad. Sci. USA 100, 9371–9376 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hooshangi, S., Thiberge, S. & Weiss, R. Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc. Natl Acad. Sci. USA 102, 3581–3586 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rappaport, N., Winter, S. & Barkai, N. The ups and downs of biological timers. Theor. Biol. Med. Model. 2, 22 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Conant, G. C. & Wagner, A. Convergent evolution of gene circuits. Nature Genet. 34, 264–266 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Dekel, E. & Alon, U. Optimality and evolutionary tuning of the expression level of a protein. Nature 436, 588–592 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Ihmels, J. et al. Rewiring of the yeast transcriptional network through the evolution of motif usage. Science 309, 938–940 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Madan Babu, M., Teichmann, S. A. & Aravind, L. Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 358, 614–633 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Dekel, E., Mangan, S. & Alon, U. Environmental selection of the feed-forward loop circuit in gene-regulation networks. Phys. Biol. 2, 81–88 (2005).

    Article  CAS  PubMed  Google Scholar 

  74. Prill, R. J., Iglesias, P. A. & Levchenko, A. Dynamic properties of network motifs contribute to biological network organization. PLoS Biol. 3, e343 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics 20, 1746–1758 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Yeger-Lotem, E. et al. Network motifs in integrated cellular networks of transcription-regulation and protein–protein interaction. Proc. Natl Acad. Sci. USA 101, 5934–5939 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhang, L. V. et al. Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network. J. Biol. 4, 6 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Lahav, G. et al. Dynamics of the p53–Mdm2 feedback loop in individual cells. Nature Genet. 36, 147–150 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Friedman, N., Vardi, S., Ronen, M., Alon, U. & Stavans, J. Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria. PLoS Biol. 3, e238 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hoffmann, A., Levchenko, A., Scott, M. L. & Baltimore, D. The IκB–NF-κB signaling module: temporal control and selective gene activation. Science 298, 1241–1245 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Nelson, D. E. et al. Oscillations in NF-κB signaling control the dynamics of gene expression. Science 306, 704–708 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Barkai, N. & Leibler, S. Circadian clocks limited by noise. Nature 403, 267–268 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Tyson, J. J., Chen, K. C. & Novak, B. Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr. Opin. Cell Biol. 15, 221–231 (2003).

    Article  CAS  PubMed  Google Scholar 

  85. Tyson, J. J., Csikasz-Nagy, A. & Novak, B. The dynamics of cell cycle regulation. Bioessays 24, 1095–1109 (2002).

    Article  CAS  PubMed  Google Scholar 

  86. Pomerening, J. R., Sontag, E. D. & Ferrell, J. E. Jr. Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nature Cell Biol. 5, 346–351 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Suel, G. M., Garcia-Ojalvo, J., Liberman, L. M. & Elowitz, M. B. An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545–550 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Ptacek, J. et al. Global analysis of protein phosphorylation in yeast. Nature 438, 679–684 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Itzkovitz, S. et al. Coarse-graining and self-dissimilarity of complex networks. Phys. Rev. E 71, 016127 (2005).

    Article  CAS  Google Scholar 

  90. Ma'ayan, A. et al. Formation of regulatory patterns during signal propagation in a mammalian cellular network. Science 309, 1078–1083 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Hertz, J., Krogh, A. & Palmer, R. G. Introduction to the Theory of Neural Computation (Perseus Books, Boulder, 1991).

    Google Scholar 

  92. Bray, D. Protein molecules as computational elements in living cells. Nature 376, 307–312 (1995).

    Article  CAS  PubMed  Google Scholar 

  93. Lund, R. D. Synaptic patterns of the superficial layers of the superior colliculus of the rat. J. Comp. Neurol. 135, 179–208 (1969).

    Article  CAS  PubMed  Google Scholar 

  94. White, E. L. Cortical Circuits (Birkhauser, Boston, 1989).

    Book  Google Scholar 

  95. White, J., Southgate, E., Thomson, J. & Brenner, S. The nervous system of Caenorhabditis elegans. Philos.Trans. R. Soc. London B Biol. Sci. 314, 1 (1986).

    Article  CAS  PubMed  Google Scholar 

  96. Itzkovitz, S. & Alon, U. Subgraphs and network motifs in geometric networks. Phys. Rev. E 71, 026117 (2005).

    Article  CAS  Google Scholar 

  97. Sporns, O. & Kotter, R. Motifs in brain networks. PLoS Biol. 2, e369 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sakata, S., Komatsu, Y. & Yamamori, T. Local design principles of mammalian cortical networks. Neurosci. Res. 51, 309–315 (2005).

    Article  PubMed  Google Scholar 

  99. Song, S., Sjostrom, P. J., Reigl, M., Nelson, S. & Chklovskii, D. B. Highly nonrandom features of synaptic connectivity in local cortical circuits. PLoS Biol. 3, e68 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Alon, U. Biological networks: the tinkerer as an engineer. Science 301, 1866–1867 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I thank my laboratory members for stimulating discussions, especially R. Milo, S. Itzkovitz, S. Mangan, S. Shen-Orr and N. Kashtan. I thank M. Elowitz, M. Surette, S. Leibler and H. Westerhoff for discussions, and the Israel Science Foundation, the Human Frontiers Science Foundation, Minerva, National Institutes of Health (USA) and the Kahn Family Foundation for support

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Alon, U. Network motifs: theory and experimental approaches. Nat Rev Genet 8, 450–461 (2007). https://doi.org/10.1038/nrg2102

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