Evolution of 'design' principles in biochemical networks.

Computer modelling and simulation are commonly used to analyse engineered systems. Biological systems differ in that they often cannot be accurately characterised, so simulations are far from exact. Nonetheless, we argue in this paper that evolution results in recurring, dynamic organisational principles in biological systems, and that simulation can help to identify them and analyse their dynamic properties. As a specific example, we present a dynamic model of the galactose utilisation pathway in yeast, and highlight several features of the model that embody such 'design principles'.

[1]  T. Kodadek,et al.  A single GAL4 dimer can maximally activate transcription under physiological conditions. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G. Odell,et al.  Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches. , 2002, The Journal of experimental zoology.

[3]  S. Johnston,et al.  Nondissociation of GAL4 and GAL80 in vivo after galactose induction. , 1992, Science.

[4]  M Ptashne,et al.  Cooperative DNA binding of the yeast transcriptional activator GAL4. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Maynard Frank Wolfe,et al.  Rube Goldberg: Inventions! , 2000 .

[6]  P. J. Bhat,et al.  Expression of human inositol monophosphatase suppresses galactose toxicity in Saccharomyces cerevisiae: possible implications in galactosemia. , 1999, Biochimica et biophysica acta.

[7]  D. Timson,et al.  Kinetic analysis of yeast galactokinase: implications for transcriptional activation of the GAL genes. , 2002, Biochimie.

[8]  J. Coleman,et al.  DNA binding and bending by the transcription factors GAL4(62*) and GAL4(149*) , 1994, Protein science : a publication of the Protein Society.

[9]  L. Serrano,et al.  Engineering stability in gene networks by autoregulation , 2000, Nature.

[10]  E. Davidson,et al.  Transcriptional regulatory cascades in development: Initial rates, not steady state, determine network kinetics , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  E. O’Shea,et al.  Global analysis of protein expression in yeast , 2003, Nature.

[12]  Henry Petroski,et al.  Design Paradigms: Case Histories of Error and Judgment in Engineering , 1994 .

[13]  G. Crabtree,et al.  Cell signaling can direct either binary or graded transcriptional responses , 2001, The EMBO journal.

[14]  Jens Nielsen,et al.  Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network , 2000, Nature Biotechnology.

[15]  G. Odell,et al.  The segment polarity network is a robust developmental module , 2000, Nature.

[16]  Michael A. Gibson,et al.  Modeling the Activity of Single Genes , 1999 .

[17]  Eberhard O. Voit,et al.  Computational Analysis of Biochemical Systems: A Practical Guide for Biochemists and Molecular Biologists , 2000 .

[18]  D. Timson,et al.  Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry. , 2002, The Biochemical journal.

[19]  S. Leibler,et al.  Robustness in simple biochemical networks , 1997, Nature.

[20]  E. Davidson.  Genomic Regulatory Systems: Development and Evolution , 2005 .

[21]  Stephen G Oliver,et al.  Dynamics of Protein Turnover, a Missing Dimension in Proteomics* , 2002, Molecular & Cellular Proteomics.

[22]  J. Hopper,et al.  Gene activation by interaction of an inhibitor with a cytoplasmic signaling protein , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Ramos,et al.  Characteristics of galactose transport in Saccharomyces cerevisiae cells and reconstituted lipid vesicles , 1989, Journal of bacteriology.

[24]  V. Iyer,et al.  Absolute mRNA levels and transcriptional initiation rates in Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Kacser,et al.  A universal method for achieving increases in metabolite production. , 1993, European journal of biochemistry.

[26]  S. Majumdar,et al.  UDPgalactose 4-epimerase from Saccharomyces cerevisiae. A bifunctional enzyme with aldose 1-epimerase activity. , 2004, European journal of biochemistry.

[27]  D. Fell.  Understanding the Control of Metabolism , 1996 .

[28]  J. Fridovich-Keil,et al.  Subcellular localization of galactose-1-phosphate uridylyltransferase in the yeast Saccharomyces cerevisiae. , 2000, Molecular genetics and metabolism.

[29]  P. J. Bhat,et al.  Quantitative Model for Gal4p‐Mediated Expression of the Galactose/Melibiose Regulon in Saccharomyces cerevisiae , 1999, Biotechnology progress.

[30]  I. Rayment,et al.  Structure and Function of Enzymes of the Leloir Pathway for Galactose Metabolism* , 2003, Journal of Biological Chemistry.

[31]  John H. Lienhard.  The Engines of Our Ingenuity: An Engineer Looks at Technology and Culture , 2000 .

[32]  M. Parthun,et al.  A transcriptionally active form of GAL4 is phosphorylated and associated with GAL80 , 1992, Molecular and cellular biology.

[33]  R. Nusse,et al.  Convergence of Wnt, beta-catenin, and cadherin pathways. , 2004, Science.

[34]  P. J. Bhat,et al.  Quantitative Analysis of GAL Genetic Switch of Saccharomyces cerevisiae Reveals That Nucleocytoplasmic Shuttling of Gal80p Results in a Highly Sensitive Response to Galactose* , 2003, Journal of Biological Chemistry.

[35]  P. Frey.  The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  P. Dey.  UDP-galactose 4′-epimerase from vicia faba seeds , 1984 .

[37]  C. Hollenberg,et al.  Galactose induction in yeast involves association of Gal80p with Gal1p or Gal3p , 1999, Molecular and General Genetics MGG.

[38]  Hans V. Westerhoff,et al.  Intracellular Glucose Concentration in Derepressed Yeast Cells Consuming Glucose Is High Enough To Reduce the Glucose Transport Rate by 50% , 1998, Journal of bacteriology.

[39]  H. Kurata,et al.  Feedback regulation of the heat shock response in E. coli , 2001, Proceedings of the 40th IEEE Conference on Decision and Control (Cat. No.01CH37228).

[40]  Gerald R. Fink,et al.  Guide to yeast genetics and molecular biology , 1993 .

[41]  P. Brown,et al.  Yeast microarrays for genome wide parallel genetic and gene expression analysis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  E. Boles,et al.  Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression. , 1997, European journal of biochemistry.

[43]  J. Hopper,et al.  Yeast regulatory gene GAL3: carbon regulation; UASGal elements in common with GAL1, GAL2, GAL7, GAL10, GAL80, and MEL1; encoded protein strikingly similar to yeast and Escherichia coli galactokinases , 1988, Molecular and cellular biology.

[44]  M. Schell,et al.  Purification and properties of galactokinase from Saccharomyces cerevisiae. , 1977, The Journal of biological chemistry.

[45]  K Lai,et al.  Overexpression of human UDP-glucose pyrophosphorylase rescues galactose-1-phosphate uridyltransferase-deficient yeast. , 2000, Biochemical and biophysical research communications.

[46]  John D. Storey,et al.  Precision and functional specificity in mRNA decay , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Y. Nogi,et al.  The enzymes of the galactose cluster in Saccharomyces cerevisiae. II. Purification and characterization of uridine diphosphoglucose 4-epimerase. , 1980, The Journal of biological chemistry.

[48]  C Jayaprakash,et al.  The role of dimerization in noise reduction of simple genetic networks. , 2003, Journal of theoretical biology.

[49]  R. Nusse,et al.  Convergence of Wnt, ß-Catenin, and Cadherin Pathways , 2004, Science.

[50]  J. Nielsen,et al.  In vivo dynamics of galactose metabolism in Saccharomyces cerevisiae: metabolic fluxes and metabolite levels. , 2001, Biotechnology and bioengineering.

[51]  T. Fukasawa,et al.  Controlled transcription of the yeast regulatory gene GAL80. , 1985, Gene.

[52]  Linda R. Petzold,et al.  Improved leap-size selection for accelerated stochastic simulation , 2003 .

[53]  A. Kotyk.  Mobility of the free and of the loaded monosaccharide carrier in Saccharomyces cerevisiae. , 1967, Biochimica et biophysica acta.

[54]  P. J. Bhat,et al.  Transcriptional control of the GAL/MEL regulon of yeast Saccharomyces cerevisiae: mechanism of galactose‐mediated signal transduction , 2001, Molecular microbiology.

[55]  D. Lohr,et al.  Transcriptional regulation in the yeast GAL gene family: a complex genetic network , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[56]  W. Bentley,et al.  Green fluorescent protein in Saccharomyces cerevisiae: real-time studies of the GAL1 promoter. , 2000, Biotechnology and bioengineering.

[57]  Calculation of half-lives of proteins in vivo. Heterogeneity in the rate of degradation of yeast proteins , 1982, Molecular and Cellular Biochemistry.

[58]  H. Xu,et al.  Gal80‐Gal80 interaction on adjacent Gal4p binding sites is required for complete GAL gene repression , 2001, The EMBO journal.

[59]  D. Gillespie.  A General Method for Numerically Simulating the Stochastic Time Evolution of Coupled Chemical Reactions , 1976 .

[60]  J. C. Belmonte,et al.  Notch activity acts as a sensor for extracellular calcium during vertebrate left–right determination , 2004, Nature.

[61]  Roger E Bumgarner,et al.  Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. , 2001, Science.

[62]  P. J. Bhat.  Galactose-1-phosphate is a regulator of inositol monophosphatase: a fact or a fiction? , 2003, Medical hypotheses.

[63]  N. Proudfoot,et al.  Poly(A) signals control both transcriptional termination and initiation between the tandem GAL10 and GAL7 genes of Saccharomyces cerevisiae , 1998, The EMBO journal.

[64]  D. Sherrington.  Stochastic Processes in Physics and Chemistry , 1983 .

[65]  L. Elsas,et al.  GALT deficiency causes UDP-hexose deficit in human galactosemic cells. , 2003, Glycobiology.

[66]  J. Leatherwood,et al.  An amino-terminal fragment of GAL4 binds DNA as a dimer. , 1989, Journal of molecular biology.

[67]  T. Segawa,et al.  The enzymes of the galactose cluster in Saccharomyces cerevisiae. Purification and characterization of galactose-1-phosphate uridylyltransferase. , 1979, The Journal of biological chemistry.

[68]  I. Sadowski,et al.  Wild type GAL4 binds cooperatively to the GAL1-10 UASG in vitro. , 1993, The Journal of biological chemistry.

[69]  D A Fell,et al.  Physiological control of metabolic flux: the requirement for multisite modulation. , 1995, The Biochemical journal.

[70]  D. Lohr,et al.  GAL4/GAL80-dependent Nucleosome Disruption/Deposition on the Upstream Regions of the Yeast GAL1-10 and GAL80 Genes (*) , 1995, The Journal of Biological Chemistry.

[71]  L. Hood,et al.  A Genomic Regulatory Network for Development , 2002, Science.

[72]  Hamid Bolouri,et al.  A method for estimating stochastic noise in large genetic regulatory networks , 2005, Bioinform..

[73]  Adam Platt,et al.  The yeast galactose genetic switch is mediated by the formation of a Gal4p–Gal80p–Gal3p complex , 1998, The EMBO journal.

[74]  A. Laughon,et al.  Isolation and preliminary characterization of the GAL4 gene, a positive regulator of transcription in yeast. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[75]  R. J. Reece,et al.  The insertion of two amino acids into a transcriptional inducer converts it into a galactokinase. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[76]  D. Chasman,et al.  Interaction of GAL4 and GAL80 gene regulatory proteins in vitro , 1987, Molecular and cellular biology.

[77]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[78]  Hamid Bolouri,et al.  Control of internal and external noise in genetic regulatory networks. , 2004, Journal of theoretical biology.

[79]  J. Hofmeyr,et al.  Regulating the cellular economy of supply and demand , 2000, FEBS letters.

[80]  J. Hopper,et al.  Evidence for Gal3p's Cytoplasmic Location and Gal80p's Dual Cytoplasmic-Nuclear Location Implicates New Mechanisms for Controlling Gal4p Activity inSaccharomyces cerevisiae , 2000, Molecular and Cellular Biology.