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© 2014 Pearson Education, Inc. Differential Expression of Genes Prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions In multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell types RNA molecules play many roles in regulating gene expression in eukaryotes

Differential Expression of Genes Prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions In multicellular

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Differential Expression of GenesProkaryotes and eukaryotes precisely regulate gene expression in response to environmental conditionsIn multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell typesRNA molecules play many roles in regulating gene expression in eukaryotes 2014 Pearson Education, Inc.1Concept 18.1: Bacteria often respond to environmental change by regulating transcriptionNatural selection has favored bacteria that produce only the products needed by that cellA cell can regulate the production of enzymes by feedback inhibition or by gene regulationOne mechanism for control of gene expression in bacteria is the operon model 2014 Pearson Education, Inc.Operons: The Basic ConceptA cluster of functionally related genes can be coordinately controlled by a single on-off switchThe switch is a segment of DNA called an operator usually positioned within the promoterAn operon is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control 2014 Pearson Education, Inc.3 The operon can be switched off by a protein repressorThe repressor prevents gene transcription by binding to the operator and blocking RNA polymeraseThe repressor is the product of a separate regulatory gene 2014 Pearson Education, Inc.4 The repressor can be in an active or inactive form, depending on the presence of other moleculesA corepressor is a molecule that cooperates with a repressor protein to switch an operon offFor example, E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan 2014 Pearson Education, Inc.5 By default the trp operon is on and the genes for tryptophan synthesis are transcribedWhen tryptophan is present, it binds to the trp repressor protein, which turns the operon off The repressor works only in the presence of its corepressor tryptophan; thus the trp operon is turned off (repressed) if tryptophan levels are high 2014 Pearson Education, Inc.6

Figure 18.3aPromoterDNAtrpRRegulatory geneRNApolymerasemRNA53ProteinInactiverepressormRNA 5(a) Tryptophan absent, repressor inactive, operon onPromotertrp operonGenes of operontrpEtrpDtrpCtrpBtrpAOperatorStart codonPolypeptide subunits that make upenzymes for tryptophan synthesisEDCB A 2014 Pearson Education, Inc.7Figure 18.3a The trp operon in E. coli: regulated synthesis of repressible enzymes (part 1: tryptophan absent)

Figure 18.3bDNAmRNAProteinActiverepressortrpRtrpETryptophan(corepressor)(b) Tryptophan present, repressor active, operon off35NoRNAmade 2014 Pearson Education, Inc.8Figure 18.3b The trp operon in E. coli: regulated synthesis of repressible enzymes (part 2: tryptophan present)Repressible and Inducible Operons:Two Types of Negative Gene RegulationA repressible operon is one that is usually on; binding of a repressor to the operator shuts off transcriptionThe trp operon is a repressible operonAn inducible operon is one that is usually off;a molecule called an inducer inactivates the repressor and turns on transcription 2014 Pearson Education, Inc. The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactoseBy itself, the lac repressor is active and switches the lac operon offA molecule called an inducer inactivates the repressor to turn the lac operon on 2014 Pearson Education, Inc.10

Figure 18.4aPromoterDNARegulatory genemRNA53OperatorRNApolymeraseActiverepressorNo RNAmadeIacZ(a) Lactose absent, repressor active, operon offProteinlacI 2014 Pearson Education, Inc.11Figure 18.4a The lac operon in E. coli: regulated synthesis of inducible enzymes (part 1: lactose absent)

Figure 18.4blacZlacYlacA(b) Lactose present, repressor inactive, operon on5DNARNA polymerasemRNA3ProteinInactiverepressorAllolactose(inducer)mRNA 5

lacIStart codonPermeaseTransacetylase-Galactosidaselac operon 2014 Pearson Education, Inc.12Figure 18.4b The lac operon in E. coli: regulated synthesis of inducible enzymes (part 2: lactose present)Video: Cartoon Rendering of the lac Repressor from E. coli

2014 Pearson Education, Inc. Inducible enzymes usually function in catabolic pathways; their synthesis is induced by achemical signalRepressible enzymes usually function in anabolic pathways; their synthesis is repressed by high levels of the end productRegulation of the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor 2014 Pearson Education, Inc.14Positive Gene RegulationSome operons are also subject to positive control through a stimulatory protein, such as catabolite activator protein (CAP), an activator of transcriptionWhen glucose (a preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP (cAMP)Activated CAP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription 2014 Pearson Education, Inc.15 When glucose levels increase, CAP detaches from the lac operon, and transcription returns to a normal rateCAP helps regulate other operons that encode enzymes used in catabolic pathways 2014 Pearson Education, Inc.16

Figure 18.5aDNAPromoterOperatorCAP-binding sitecAMPActiveCAPInactiveCAPRNApolymerasebinds and transcribeslacIAllolactoseInactive lacrepressor(a) Lactose present, glucose scarce (cAMP level high):abundant lac mRNA synthesizedlacZ 2014 Pearson Education, Inc.17Figure 18.5a Positive control of the lac operon by catabolite activator protein (CAP) (part 1: glucose scarce)

Figure 18.5bPromoterDNAlacZCAP-binding siteRNApolymerase lesslikely to bindOperatorInactiveCAPInactive lacrepressor(b) Lactose present, glucose present (cAMP level low):little lac mRNA synthesizedlacI 2014 Pearson Education, Inc.18Figure 18.5b Positive control of the lac operon by catabolite activator protein (CAP) (part 2: glucose present)Operons that can be turned on or off are inducible or repressableOperons that are always on are called constitutive 2014 Pearson Education, Inc.On unless specifically turned off = negative control example = repressor action in the lac operonOff unless specifically turned on = positive control example = CAP protein in lac operon

2014 Pearson Education, Inc.