Operon Theory

9 Key excerpts on "Operon Theory"

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  Emergent Collective Properties, Networks and Information in Biology

  • J. Ricard, Giorgio Bernardi(Authors)
  • 2006(Publication Date)
  • Elsevier Science

    (Publisher)

  1. An overview of the archetype of gene networks: the bacterial operons E. coli can grow on lactose as a sole source of carbon. An enzyme, -galactosidase, hydrolyzes lactose to glucose and galactose. In fact, the presence of lactose in the growth medium induces the synthesis of new molecules of -galactosidase. Two other proteins, a membrane protein called galactoside permease and a thiogalacto- sidase transacetylase, are also synthesized together with -galactosidase. Moreover, as soon as -galactosidase appears, the two other proteins are synthesized in constant proportions whatever be the experimental conditions. J. Ricard Emergent Collective Properties, Networks, and Information in Biology ß 2006 Elsevier B.V. All rights reserved DOI: 10.1016/S0167-7306(05)40010-1 1.1. The operon as a coordinated unit of gene expression The basic concepts of how regulation is achieved in bacteria relies upon the seminal work of Jacob and Monod [1–3]. They proposed that two types of DNA sequences exist in bacteria: sequences coding for trans-acting products, and cis-acting sequences. Any gene product, usually a protein, that recognizes its target is defined as trans-acting. Cis-acting sequences are DNA sequences that are active as such in the chromosome [4]. Among the trans-acting sequences is a so-called regulator gene which is expressed as mRNA itself translated as a protein. In the Jacob–Monod model, this protein can be identified to the repressor that binds to a specific region of the DNA called operator (Fig. 1). This process prevents RNA polymerase from binding to its specific site called promoter hence impeding the transcription of a battery of structural genes, viz. those that, in E. coli, code for -galactosidase, permease, and transacetylase. In bacteria, the promoter and operator can be A Regulatory region Structural genes RNA pol.

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  Further Milestones in Biochemistry

  • M.G. Ord, L.A. Stocken(Authors)
  • 1997(Publication Date)
  • Elsevier Science

    (Publisher)

  Chapter 8 REGULATION OF EXPRESSION OF MICROBIAL GENES Patricia H. Clarke Introduction 239 Adaptation 240 Genes and Enzymes 246 From Growth to Enzyme Adaptation 251 Enzyme Adaptation in 1953 253 The Permease Concept 256 Towards the Operon Theory 258 The Operon Model: 1961 262 Other Operons 265 Complex Operon Regulation 270 Manipulating Genes 272 References 273 INTRODUCTION In 1961 Francois Jacob^^ and Jacques Monod^^ published the review Genetic Regulatory Mechanisms in the Synthesis of Proteins in the third volume of the still infant Journal of Molecular Biology and opened up an entirely new way of thinking about genes and enzymes. Most of the paper was concerned with experiments with the bacterial enzyme, )3-galactosidase, but the authors pointed out that their model of bacterial gene regulation had much wider implications: Enzymatic adaptation, as studied in microorganisms, offers a valuable model for the interpretation of biochemical coordination within tissues and between organs in higher organisms. 239 240 PATRICIA H. CURKE It was to be many years before the Jacob-Monod model could be tested in higher organisms and many surprises and complexities would appear. But questions about adaptation in microorganisms, particularly in relation to bacterial metabolism, had long been exercising microbial biochemists. During the 1950s a series of papers on the )8-galactosidase of Escherichia coli had emerged from the Pasteur^ Institute in Paris and rumors were rife about a new and exciting theory. The definitive review had been eagerly awaited. In essence, the model proposed that the expression of a structural gene for an enzyme was prevented by repression by the product of its regulator gene unless, and until, an appropriate inducing molecule appeared in the growth environment. The two authors had already presented their ideas at several well-attended lectures and Frangois Jacob delighted the audience at one lecture with the following analogy.

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  Eukaryotic Gene Regulation

  Volume I

  • Gerald M. Kolodny(Author)
  • 2018(Publication Date)
  • CRC Press

    (Publisher)

  Such considerations made clear from the onset that a “quantum jump” is involved in passing from the organization of prokaryotic regulation to eukaryotic systems. Not only is the effort of section greatly increased, but in addition, we touch the limits of the feasibility of a system of direct selection which, as in any mechanism subject to physical reality, is limited by problems of resolution vs. noise. Therefore, every one of the early models of eukaryotic gene regulation tried to cope with the problem of the high selectivity necessary to handle the high numbers of genes involved and to propose means of reducing the selection effort, i.e., the energy a cell or organism has to spend for regulation (cf. discussion in References 5, 6, 12, and 13).

  FIGURE 7. Integration of information transfer into the general circuitry of the cell. Individual circuits within the chain of 1IT are integrated into other metabolic chains of the cell; at one or several points, an individual biochemical reaction links a given information carrier to, e.g., energy metabolism, transport mechanism, architecture (morphology), etc. Of particular importance are reactions integrating the progress of specific information transfer into the general network of control. In consequence, all these phenomena are linked, and changes in dynamic equilibrium in any of these chains — at any level — modulated by the biochemical equilibrium governing the joining reaction, may influence the chain of information transfer.

  There is a logical argument excluding a priori the possibility that every gene is under control of an individual, exclusive, and specific regulator: the escalating properties of a system where regulators have to be regulated themselves emphasizes the necessity for schemes allowing reduction in the number of regulative signals relative to the number of genes to be controlled. Principles of convergence in selection have to be adopted which allow the control of several genes by a single signal. The bacterial operon is one solution to this problem: the operator/repressor signal has pleiotropic effects in governing simultaneously several genes. The condition for function, in this case, is the physical linkage of the battery of genes which constitute a program built into “hardware”.

  The inexistence in eukaryotes of the classical operon calls for the action of pleiotropic regulatory signals involved in the control of several genes at the level of DNA, of pre-mRNA, and of mRNA. Since individual genes must eventually be singled out, e.g., globin a chain message from globin (β chain message, one has to assume that combinations of such pleiotropic signals will provide, eventually, individual signification. This assumption leads immediately to the logical deduction that a specific regulative code

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  Molecular Pathology

  • Antoni Horst(Author)
  • 2018(Publication Date)
  • CRC Press

    (Publisher)

  Chapter 4 GENE REGULATION I. GENE REGULATION IN PROKARYOTES

  As a rule proteins can be divided into two: (1) constitutive synthesized by cells in fixed amounts, independent of need, and (2) inducible or repressible whose synthesis is dependent on the regulatory mechanisms of adequate genes. Generally, the first group is necessary for basic life processes, and the second group for specific functions, e.g., enzymes necessary for degradation of lactose by E. coli are useless in a medium without this sugar, but in a medium containing lactose (without these enzymes lactose cannot be utilized).

  First, Jacob and Monod1 performed experiments upon inducible and repressible enzyme systems in bacteria. These systems were well-known for over 60 years when it was observed that in the presence of a specific substrate (e.g., lactose) enzymes necessary for their degradation were synthesized, and in the absence of the substrate, these enzymes disappeared. This effect, named “enzymatic adaptation” was the subject of many experiments and speculations until the experiments of Jacob and Monod threw some light upon the essence of this phenomenon.

  The main idea of these experiments was the operon model comprising enzymes which catalyze the given biochemical reaction, directed by a specific regulatory mechanism. Enzymes are synthesized on the basis of genes which determine their structure, therefore named “structural genes”. The regulatory mechanism is composed of specific regulatory genes, preceding the structural genes. The structural genes and the regulatory genes compose a unit, named “operon”. The regulatory genes occur normally far from the structural genes.

  The regulatory genes make some kind of switching mechanism which turns on and off a whole set of structural genes of the given operon. Turning “on” causes transcription of the structural genes, and turning “off” stops their transcription. Transcription of structural genes in a bacterial operon follows in an uninterrupted manner, and a polycistronic mRNA is synthesized, i.e., a long RNA molecule containing mRNAs for the entire set of enzymes, necessary to perform the given biochemical reaction. The polycistronic character of the synthesized mRNA tells us: mutation in the regulatory region causes partial or total inhibition of expression of all enzymes in the operon; mutation in the early region of transcription causes inhibition of transcription of all the following (located downstream) genes of the operon; transcription of all the structural genes is coordinated.

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  Biochemistry

  An Integrative Approach with Expanded Topics

  • John T. Tansey(Author)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  When bacteria face various environmental challenges (for example, changes in nutrient levels, osmolarity, or temperature), they can respond by synthesizing different sigma factors, and as many as 14 such factors have been identified. For example, when presented with increased temperature in its environment, the cell produces s32, a sigma factor with a molecular weight of 32 kDa. This factor binds to the heat shock promoter sequences, activating transcription in these genes, which in turn produce proteins that the cell uses to respond to this challenge. Sigma factors are involved in the pathogenicity, or virulence, of bacteria and can globally influence the genes being expressed. Particular sigma factors can upregulate the genes involved in resistance to stressful environments, such as heat, low pH, or the high concentrations of hydrogen peroxide sometimes seen in abscessed tissue. For example, a common problem associated with cystic fibrosis is bacterial infections that produce significant amounts of mucus. A specific sigma factor has been found that upregulates genes involved in producing secreted polysaccharides (alginate) associated with this mucus.

  17.2.2 Operons regulate small groups of genes that code for proteins with a common purpose

  Often, the cell needs to respond to a challenge that requires a more focused approach than simply changing the types of sigma factors synthesized. One such instance would be a shift in the availability of different food sources. An organism would be at a disadvantage if it were forced to produce all the enzymes needed to metabolize a diverse array of carbohydrates at all times or if it were unable to switch from one carbon source to another (for example, from glucose to lactose). Operons provide one way in which prokaryotes can respond to such a challenge.

  An operon is an organization of genes that code for proteins involved in a common purpose, such as the metabolism of a specific carbohydrate or amino acid (Figure 17.2 ). Within an operon, the promoter region serves as a control site to regulate the synthesis of a single mRNA that codes for all the genes for proteins involved in the specific metabolic pathway. The promoter region binds to RNA polymerase. The operator region binds to repressor proteins encoded by genes upstream of the promoter to regulate transcription of the structural genes that follow in the message. The operon allows the regulation (either positive or negative) of related genes to be accomplished by a single control region, rather than multiple control sequences regulating multiple independent genes. The end result is a single polycistronic message , that is, a message that contains multiple start and stop sites and codes for more than one protein. Operons also have regions upstream of the control sites that code for a regulatory protein (the repressor). Often, these proteins will bind a metabolite involved in the pathway specific to the operon and regulate the expression of the operon structural genes either positively or negatively. By binding different regulatory elements, genes can be either up- or downregulated, as appropriate. The remainder of this section examines two examples of operons: the lac operon and the trp

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  Molecular Genetics of Bacteria

  • Jeremy W. Dale, Simon F. Park(Authors)
  • 2013(Publication Date)
  • Wiley

    (Publisher)

  lacI gene which codes for a repressor protein, are connected with the inducibility of the operon which is described later in this chapter.

  In some cases, coordinated control of several genes is achieved by a single operator site that regulates two promoters facing in opposite directions (Figure 3.5 ). In one example, the genes ilvC (coding for an enzyme needed for isoleucine and valine biosynthesis) and ilvY (which codes for a regulatory protein) are transcribed in opposite directions (they are divergent genes), but transcription of both genes is controlled by a single operator. Since there is a single operator, and the genes are therefore coordinately controlled, this is also referred to as an operon, even though there are two distinct mRNA molecules. This provides an exception to the general rule that genes in an operon are transcribed into a single mRNA.

  Figure 3.4 Structure of the lac operon.

  Figure 3.5 Structure of operons and regulons.

  Not all coordinately controlled genes are arranged in operons. In some cases, groups of genes at different sites on the chromosome are regulated in a concerted fashion. Such a set of genes or operons, expressed from separate promoter sites but controlled by the same regulatory molecule, is called a regulon (Figure 3.5 ). For example, arginine biosynthesis requires eight genes (argA–H ), but (in E. coli ) only three of these (argC, argB , and argH ) form an operon with a single promoter. A fourth gene (argE ) is divergently transcribed from an adjacent promoter (thus providing another example of a divergent operon as described above) while the remaining three genes (argA, argF , and argG

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  Microbiology

  • Dave Wessner, Christine Dupont, Trevor Charles, Josh Neufeld(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  In earlier chapters, we learned how researchers determined that DNA was the genetic material, discovered genetic mechanisms in bacteria, and revealed the structure of DNA. They also formulated the idea of gene regulation using this knowledge. Indeed, the 1965 Nobel Prize for Physiology or Medicine was awarded to François Jacob, André Lwoff, and Jacques Monod in recognition of their discoveries regarding genetic regulation in bacteria and bacteriophages. These French researchers, working at the Institut Pasteur in Paris, struck on a visionary idea: that cells only produced enzymes when they needed to. In their great example, they noted that Escherichia coli much preferred to use glucose than lactose, the milk sugar. Furthermore, the enzyme for degrading lactose was only detectable when lactose was present and glucose was absent. In following up on this idea, they proposed the operon concept, which describes a mechanism by which regulatory genes can direct cell metabolism by altering rates of transcription of structural genes. The discovery of gene regulation in E. coli had far-reaching impact on the understanding of the living world, as foreshadowed by the famous quote from Jacques Monod, “What is true for E. coli is also true for the elephant.” These types of insights made the Institut Pasteur a mecca for many young scientists from around the world. Through a series of elegant genetic experiments, and driven by intuition, these scientists showed for the first time that genes can be turned on and off. By studying the control of metabolism of lactose, and also the control of infection of E. coli by the lambda (λ) bacteriophage, they deduced the fundamental nature of gene regulation and discovered genes whose sole role was to regulate expression of other genes. Since these early discoveries, scientists have studied numerous gene regulatory systems in an assortment of microbes

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  Molecular Biology

  Structure and Dynamics of Genomes and Proteomes

  • Jordanka Zlatanova(Author)
  • 2023(Publication Date)
  • Garland Science

    (Publisher)

  We have already discussed the local control of individual operons. The DNA-binding proteins that regulate specific operons are usually highly specific to the regulatory regions of the respective operon and are present in relatively small amounts, sometimes only a few molecules per cell. A higher level of control is seen when sets of operons form regulons, whose expression is regionally controlled. The operons constituting a regulon participate in a common function, such as utilization of nitrogen or carbon, and share common regulators, either activators or repressors, that recognize DNA sequences common to all member operons and respond to nutrient or environmental conditions. The regulon regulators are more abundant than those of individual operons and bind to multiple targets. Regulation of the heat-shock regulon is an example (see Figure 9.11). This regulation involves the use of alternative σ factors in succession, with σ 32/H being the factor recognizing the promoters of heat-shock operons. Multiple regulons may also be controlled in coordination; sets of such regulons have been termed stimulons or modulons. Operons in a modulon may be under individual controls as well as under the control of common, pleiotropic, regulatory proteins. For example, the CAP modulon contains all regulons and operons, including the lac operon and the ara regulon, that are regulated by cAMP-bound CAP; each operon has other regulators as well. Finally, there are global controls of overall expression patterns (Figure 11.19). The global level of DNA supercoiling represents one such global control. Figure 11.19 Transcriptional regulatory network of E. coli. (A) Operons can be organized into modules; different modules are shown in different colors. The ten global regulators shown inside the oval form the core part of the network. The peripheral modules are connected mainly through the global regulators

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  Snyder and Champness Molecular Genetics of Bacteria

  • Tina M. Henkin, Joseph E. Peters(Authors)
  • 2020(Publication Date)
  • ASM Press

    (Publisher)

  ara operon expression in all but a few cells (panel C), and the proportion of fluorescent cells increases as the concentration of arabinose increases (panels B and A). Individual cells turn on expression during the incubation period (compare left to right for each concentration), rather than a general increase in fluorescence of every cell (see Fritz et al., Suggested Reading). © 2014 Fritz et al. CC-BY 4.0.

  THE DNA OF A CELL contains thousands to hundreds of thousands of genes, depending on whether the organism is a relatively simple single-celled bacterium or a complex multicellular eukaryote, like a human. All of the features of the organism are due, either directly or indirectly, to the products of these genes. However, all the cells of a multicellular organism do not always look or act the same, despite the fact that they share essentially the same genes. Even the cells of a single-celled bacterium can look or act differently depending on the conditions under which the cells find themselves, because the genes of a cell are expressed at different levels. The process by which the expression of genes is turned on and off at different times and under different conditions is called the regulation of gene expression .

  Cells regulate the expression of their genes for many reasons. A cell may express only the genes that it needs in a particular environment so that it does not waste energy making RNAs and proteins that are not needed at that time, or the cell may turn off genes whose products might interfere with other processes going on in the cell at the time. Cells also regulate their genes as part of developmental processes, such as sporulation. Genes can be expressed independently, as monocistronic units, or their expression can be coordinated through cotranscription in a polycistronic unit, or operon (see chapter 2 ). Groups of genes and operons can also be coordinately regulated via global regulatory mechanisms.

  As described in chapter 2

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