Summing up the noise in gene networks

Random fluctuations in genetic networks are inevitable as chemical reactions are probabilistic and many genes, RNAs and proteins are present in low numbers per cell. Such ‘noise’ affects all life processes and has recently been measured using green fluorescent protein (GFP). Two studies show that negative feedback suppresses noise, and three others identify the sources of noise in gene expression. Here I critically analyse these studies and present a simple equation that unifies and extends both the mathematical and biological perspectives.

[1]  E. Schrödinger.  What Is Life , 1946 .

[2]  A. Novick,et al.  ENZYME INDUCTION AS AN ALL-OR-NONE PHENOMENON. , 1957, Proceedings of the National Academy of Sciences of the United States of America.

[3]  U N Singh,et al.  Polyribosomes and unstable messenger RNA: a stochastic model of protein synthesis. , 1969, Journal of theoretical biology.

[4]  M. Savageau.  Biochemical systems analysis. II. The steady-state solutions for an n-pool system using a power-law approximation. , 1969, Journal of theoretical biology.

[5]  M. Savageau,et al.  Parameter Sensitivity as a Criterion for Evaluating and Comparing the Performance of Biochemical Systems , 1971, Nature.

[6]  P. Maloney,et al.  Distribution of suboptimally induces -D-galactosidase in Escherichia coli. The enzyme content of individual cells. , 1973, Journal of molecular biology.

[7]  M. Savageau.  Comparison of classical and autogenous systems of regulation in inducible operons , 1974, Nature.

[8]  W. Schieve,et al.  Stochastic model of linear, continuous protein synthesis in bacterial populations. , 1977, Journal of theoretical biology.

[9]  O. Berg.  A model for the statistical fluctuations of protein numbers in a microbial population. , 1978, Journal of theoretical biology.

[10]  N. Kampen,et al.  Stochastic processes in physics and chemistry , 1981 .

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

[12]  H. Westerhoff,et al.  Thermodynamics and Control of Biological Free-Energy Transduction , 1987 .

[13]  S. Leibler,et al.  Physical aspects of the growth and regulation of microtubule structures. , 1993, Physical review letters.

[14]  O. Berg.  Periodic selection and hitchhiking in a bacterial population. , 1995, Journal of theoretical biology.

[15]  W. Ebeling.  Stochastic Processes in Physics and Chemistry , 1995 .

[16]  J. Peccoud,et al.  Markovian Modeling of Gene-Product Synthesis , 1995 .

[17]  H. Kacser,et al.  The control of flux. , 1995, Biochemical Society transactions.

[18]  A. Arkin,et al.  Stochastic mechanisms in gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Araceli M. Huerta,et al.  From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli. , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[20]  A. Løbner-Olesen,et al.  Distribution of minichromosomes in individual Escherichia coli cells: implications for replication control , 1999, The EMBO journal.

[21]  M. Ehrenberg,et al.  Stochastic focusing: fluctuation-enhanced sensitivity of intracellular regulation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[22]  D. Chattoraj,et al.  Control of plasmid DNA replication by iterons: no longer paradoxical , 2000, Molecular microbiology.

[23]  M. Ehrenberg,et al.  Fluctuations and quality of control in biological cells: zero-order ultrasensitivity reinvestigated. , 2000, Biophysical journal.

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

[25]  M. Thattai,et al.  Intrinsic noise in gene regulatory networks , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Ehrenberg,et al.  Noise in a minimal regulatory network: plasmid copy number control , 2001, Quarterly Reviews of Biophysics.

[27]  T. Kepler,et al.  Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. , 2001, Biophysical journal.

[28]  R. Zwanzig.  Nonequilibrium statistical mechanics , 2001, Physics Subject Headings (PhySH).

[29]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[30]  P. Swain,et al.  Intrinsic and extrinsic contributions to stochasticity in gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Jeffrey Mervis.  Big Facilities Account Is Big Headache for NSF , 2002, Science.

[32]  Ertugrul M. Ozbudak,et al.  Regulation of noise in the expression of a single gene , 2002, Nature Genetics.

[33]  Johan Paulsson,et al.  Multileveled selection on plasmid replication. , 2002, Genetics.

[34]  S. Leibler,et al.  Mechanisms of noise-resistance in genetic oscillators , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  X. Xie,et al.  Single-molecule approach to dispersed kinetics and dynamic disorder: Probing conformational fluctuation and enzymatic dynamics , 2002 .

[36]  Peter G Wolynes,et al.  Stochastic gene expression as a many-body problem , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Elf,et al.  Fast evaluation of fluctuations in biochemical networks with the linear noise approximation. , 2003, Genome research.

[38]  Andrew D Rutenberg,et al.  Pattern formation inside bacteria: fluctuations due to the low copy number of proteins. , 2003, Physical review letters.

[39]  Mads Kærn,et al.  Noise in eukaryotic gene expression , 2003, Nature.

[40]  Johan Paulsson,et al.  Near-critical phenomena in intracellular metabolite pools. , 2003, Biophysical journal.

[41]  E. Schrödinger,et al.  What is life? : the physical aspect of the living cell , 1946 .

[42]  Jeffrey W. Smith,et al.  Stochastic Gene Expression in a Single Cell , 2022 .