Abstract
Systems analysis has historically been performed in many areas of biology, including ecology, developmental biology and immunology. More recently, the genomics revolution has catapulted molecular biology into the realm of systems biology. In unicellular organisms and well-defined cell lines of higher organisms, systems approaches are making definitive strides toward scientific understanding and biotechnological applications. We argue here that two distinct lines of inquiry in molecular biology have converged to form contemporary systems biology.
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References
Umbarger, H.E. & Brown, B. Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases. J. Bacteriol. 73, 105–12 (1957).
Yates, R.A. & Pardee, A.B. Control by uracil of formation of enzymes required for orotate synthesis. J. Biol. Chem. 227, 677–692 (1957).
Beckwith, J.R. Regulation of the lac operon. Recent studies on the regulation of lactose metabolism in Escherichia coli support the operon model. Science 156, 597–604 (1967).
Hunkapiller, T. et al. Large-scale and automated DNA sequence determination. Science 254, 59–67 (1991).
Rowen, L., Magharias, G. & Hood, L. Sequencing the human genome. Science 278, 605–607 (1997).
Scherf, M., Klingenhoff, A. & Werner, T. Highly specific localization of promoter regions in large genomic sequences by PromoterInspector: a novel context analysis approach. J. Mol. Biol. 297, 599–606 (2000).
Uetz, P. et al. A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).
Ge, H., Walhout, A.J. & Vidal, M. Integrating 'omic' information: a bridge between genomics and systems biology. Trends Genet. 19, 551–560 (2003).
Palsson, B.O. In silico biology through 'omics'. Nat. Biotechnol. 20, 649–650 (2002).
Schrödinger, E. What is life? The physical aspects of the living cell. Based on Lectures Delivered under the Auspices of the Dublin Institute for Advanced Studies at Trinity College, Dublin, in February 1943. (Cambridge University Press, Cambridge, UK, 1944). http://home.att.net/∼p.caimi/oremia.html
Onsager, L. Reciprocal relations in irreversible processes. Phys. Rev. 37, 405–426 (1931).
Rottenberg, H., Caplan, S.R. & Essig, A. Stoichiometry and coupling: theories of oxidative phosphorylation. Nature 216, 610–611 (1967).
Westerhoff, H.V. & Van Dam, K. Thermodynamics and Control of Biological Free-Energy Transduction (Elsevier, Amsterdam, 1987).
Mitchell, P. Chemiosmotic Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191, 144–148 (1961).
Mitchell, P. Coupling in Oxidative and Photosynthetic Phosphorylation. (Glynn Research Ltd., Bodmin, UK, 1966).
Turing, A. The chemical basis of morphogenesis. Phil. Trans. Roy. Soc. London, Ser. B 237, 37–72 (1952).
Glansdorff, P. & Prigogine, I. Structure, Stabilité et Fluctuations (Masson, Paris, 1971).
Lawrence, P.A. The Making of a Fly (Blackwell, London, 1992).
Chance, B., Estabrook, R.W. & Ghosh, A. Damped sinusoidal oscillations of cytoplasmic reduced pyridine nucleotide in yeast cells. Proc. Natl. Acad. Sci. USA 51, 1244–1251 (1964).
Hess, B. & Boiteux, A. Oscillatory phenomena in biochemistry. Annu. Rev. Biochem. 40, 237–258 (1971).
Teusink, B., Bakker, B.M. & Westerhoff, H.V. Control of frequency and amplitudes is shared by all enzymes in three models for yeast glycolytic oscillations. Biochim. Biophys. Acta. 1275, 204–212 (1996).
Wolf, J. et al. Transduction of intracellular and intercellular dynamics in yeast glycolytic oscillations. Biophys. J. 78, 1145–1153 (2000).
Tyson, J.J. & Murray, J.D. Cyclic AMP waves during aggregation of Dictyostelium amoebae. Development 106, 421–426 (1989).
Goodwin, B.C. Oscillatory Organization in Cells, a Dynamic Theory of Cellular Control Processes (Academic Press, New York, 1963).
Garfinkel, D. et al. Computer applications to biochemical kinetics. Annu. Rev. Biochem. 39, 473–498 (1970).
Loomis, W. & Thomas, S. Kinetic analysis of biochemical differentiation in Dictyostelium discoideum. J. Biol. Chem. 251, 6252–6258 (1976).
Wright, B.E. The use of kinetic models to analyze differentiation. Behavioral Sci. 15, 37–45 (1970).
Heinrich, R., Rapoport, S.M. & Rapoport, T.A. Progr. Biophys. Mol. Biol. 32, 1–83 (1977).
Joshi, A. & Palsson, B.O. Metabolic dynamics in the human red cell. Part I—A comprehensive kinetic model. J. Theor. Biol. 141, 515–528 (1989).
Novak, B. & Tyson, J.J. Quantitative analysis of a molecular model of mitotic control in fission yeast. J. Theor. Biol. 173, 283–305 (1995).
Edwards, J.S. & Palsson, B.O. Systems properties of the Haemophilus influenzae Rd metabolic genotype. J. Biol. Chem. 274, 17410–17416 (1999).
Kacser, H. & Burns, J.A. In Rate Control of Biological Processes (ed., Davies, D.D.) 65–104 (Cambridge University Press, Cambridge, 1973).
Groen, A.K., Wanders, R.J.A., Van Roermund, C., Westerhoff, H.V. & Tager, J.M. Quantification of the contribution of various steps to the control of mitochondrial respiration. J. Biol. Chem. 257, 2754–2757 (1982).
Savageau, M.A. Biochemical Systems Analysis (Addison-Wesley, Reading, MA, 1976).
Westerhoff, H.V. & Chen, Y. How do enzyme activities control metabolite concentrations? An additional theorem in the theory of metabolic control. Eur. J. Biochem. 142, 425–430 (1984).
Westerhoff, H.V., Hofmeyr, J.H. & Kholodenko, B.N. Getting to the inside of cells using metabolic control analysis. Biophys. Chem. 50, 273–283 (1994).
Papin, J.A., Price, N.D., Wiback, S.J., Fell, D.A. & Palsson, B.O. Metabolic pathways in the post-genome era. Trends Biochem. Sci. 28, 250–258 (2003).
Kholodenko, B.N. & Westerhoff, H.V. (eds.) Metabolic Engineering in the Post Genomics Era (Horizon Bioscience, UK, 2004).
Bakker, B.M. et al. Network-based selectivity of antiparasitic inhibitors. Mol. Biol. Rep. 29, 1–5 (2002).
Ibarra, R.U., Edwards, J.S. & Palsson, B.O. Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth. Nature 420, 186–189 (2002).
Acknowledgements
We thank Adam Arkin for comments and Timothy Allen for editing. B.O.P. serves on the scientific advisory board of Genomatica, Inc.
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Westerhoff, H., Palsson, B. The evolution of molecular biology into systems biology. Nat Biotechnol 22, 1249–1252 (2004). https://doi.org/10.1038/nbt1020
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DOI: https://doi.org/10.1038/nbt1020
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