operon

[OPER(ATOR) + -ON¹.]

For more information on operon, visit Britannica.com.

A group of distinct genes that are expressed and regulated as a unit. Each operon is a deoxyribonucleic acid (DNA) sequence that contains at least two regulatory sites, the promoter and the operator, and the structural genes that code for specific proteins (see illustration). The promoter (p) site is the location at which ribonucleic acid (RNA) polymerase binds to the operon. RNA polymerase moves down the operon catalyzing the synthesis of a messenger RNA (mRNA) molecule with a sequence that is complementary to DNA. This process is called transcription. The mRNA is used as a template by ribosomes to synthesize the proteins coded for by the structural genes (in the original DNA) in a process called translation. This mRNA is referred to as polycistronic because its sequence directs the synthesis of more than one protein. The operator (o) site is located between the p site and the beginning of the coding region for the first structural gene. It is at this site that molecules called repressors can bind to the DNA and block RNA polymerase from transcribing the DNA, thus shutting off the operon. Some systems can be derepressed by the addition of small molecules called effectors, which bind to the repressor protein and cause a conformational (shape) change that makes it no longer able to bind to the DNA at the operator site. See also Deoxyribonucleic acid (DNA); Ribonucleic acid (RNA).

repressor gene; p is the promoter site; and o is the operator site. The arrow indicates length and direction of mRNA synthesis.">
The lactose (lac) operon from Escherichia coli: z, y, and a are structural genes; i is the lac repressor gene; p is the promoter site; and o is the operator site. The arrow indicates length and direction of mRNA synthesis.

Activation is believed to arise from the binding of a protein immediately adjacent to the promoter. The protein provides additional locations with which RNA polymerase can interact; the extra interactions result in an increased amount of polymerase binding to the promoter. Activators are more frequently involved in the regulation of genes in eukaryotes than in prokaryotes.

Once RNA polymerase begins transcribing a gene, it continues making RNA until a termination site is reached. Antiterminators are proteins that prevent termination at certain sites. In the presence of these antiterminators, RNA polymerase continues along the genome and transcribes the genes following the termination site until a different class of termination site is encountered.

Attenuation is the premature termination of the mRNA translation. Although the exact mechanism of attenuation has not been determined, it is thought that attenuation is due to the formation of a translation termination site in mRNA. See also Gene; Gene action.

A segment of DNA consisting of an operator gene and one or more structural genes with related functions controlled by the operator gene in conjunction with a regulator gene.

An operon is a genetic regulatory system found in prokaryotes and the bacterial viruses (bacteriophages) that attack bacteria. It is a cluster of genes that share regulatory elements and are usually functionally related.

The Discovery of Operons

French scientists Jacques Monod and François Jacob first coined the term "operon" in a short paper published in 1960 in the Proceedings of the French Academy of Sciences. They elaborated the concept of the operon in several papers that appeared in 1961, based on their studies on the lac genes (genes for the metabolism of lactose sugar) of the bacterium Escherichia coli and the genes of bacteriophage lambda. Monod and Jacob received the Nobel Prize in 1985 for this work.

Typical Features of Operons

The genes of an operon are usually functionally related. Genes are the basic unit of biological information, and consist of specific segments of deoxyribonucleic acid (DNA). The segments of DNA that constitute a gene consist of distinctive sets of nucleotide pairs located in a discrete region of a chromosome that encodes a particular protein. Within an operon, the genes encode proteins that execute related functions. For example, the five genes of the tryptophan (trp) operon in E. coli each encode one of the enzymes necessary for the biosynthesis of the amino acid tryptophan from a metabolite called chorismate. This condition is mimicked in many bacteria.

Exceptions do occur; the genes of some operons may lack an obvious functional relationship. For example one operon in E. coli contains one gene that encodes a ribosomal protein S21 (rpsU), another that encodes DNA primase (dnaG), and one that encodes the sigma subunit of RNA polymerase (rpoD). The protein products of these genes are all involved in starting up the synthesis of macromolecules, but beyond that they have no obvious functional relationships to one another. Nonetheless, the clustering of these genes and their common regulation qualify them to be treated as elements of a single operon.

Another common feature of operons is that their genes are clustered on the bacterial chromosome. This chromosome is a large circular molecule of DNA. The genes of an operon are arranged in a consecutive and linear fashion at a specific location on the bacterial chromosome.

In the case of the lactose utilization (lac) operon of E. coli, three genes necessary for the successful utilization of the disaccharide lactose, a common sugar found in milk, are arranged in a linear fashion on the chromosome (see Figure 1). The lacZ gene, which encodes the lactose-degrading enzyme, β-galactosidase, is directly followed by the lacY gene, which encodes a membrane protein, called lactose permease, that allows the entry of lactose into the cell. The lacY gene is immediately followed by the lacA gene, which encodes the thiogalactoside acetyltransferase enzyme that detoxifies lactose-related compounds that might be toxic to the cell. The linear arrangement of these functionally related genes is a hallmark of an operon. The arrangement is significant because the proteins made from these genes will all be easily turned on in concert, so that lactose metabolism proceeds rapidly and efficiently.

Other Typical Characteristics

The clustered genes of the operon typically share a common promoter and a common regulatory region, called an operator. Gene expression requires the enzyme RNA polymerase to transcribe (synthesize an RNA copy of) the gene. This RNA copy is called a messenger RNA (mRNA), which is translated by ribosomes to produce the protein encoded by the gene. In all genes, RNA polymerase begins transcription at a specific site or sequence called the promoter (designated "P" in Figure 1). The genes in an operon usually share a common promoter from which the genes of the operon are transcribed.

Operons almost always contain a common promoter region, but not all operons contain only a single promoter. For example the E. coli operon for galactose utilization (gal) contains two promoters. One of these promoters is active in the presence of glucose, and the other is not (both glucose and galactose are sugars). Some operons, like the trp and isoleucine-valine (ilv) operons, both from E. coli, also have internal promoters that allow the expression of some but not all of the genes in the operon. (Isoleucine and valine are amino acids.)

Operons also have one or more control regions, called operators, that mediate the expression of the genes in the operon (the operator is designated "O" in Figure 1). Like a promoter, an operator is a site on the DNA, but it does not bind with RNA polymerase. Operators function in one of two ways. They can contain DNA sequences that specifically bind particular proteins. Once bound onto DNA, these proteins can prevent the expression of the operon by interfering with the action of RNA polymerase, as in the case of the lac repressor. Other proteins bound on other operons can greatly enhance the expression of the operon, as in the case of the AraC protein. Operators can thus prevent or facilitate gene expression.

Instead of acting as target sites for DNA-binding proteins, operators also act as the sites of regulation by attenuation. Amino acid biosynthesis operons such as trp are usually regulated by attenuation. In such operons the operator provides both a start site for transcription and a ribosome-binding site for the synthesis of a short leader peptide. Through a clever mechanism, the presence of sufficient amino acid in the cell causes the ribosome to disrupt transcription. When the supply of the amino acid is low, transcription of the operon continues without interruption. In this way, if the proteins coded for by the operon genes are needed to synthesize amino acids, then early transcriptional termination does not occur. If they are not needed, because the amino acid is already present, then early termination ensues. This prevents the wasteful production of unnecessary proteins.

The genes of an operon also show a common mode of regulation. The clustering of the genes of an operon and the related functions of these genes requires a mode of regulation that equally affects all the genes of the operon. In the case of the lac operon of E. coli, the product of the lacI gene is a DNA-binding protein that specifically binds to the lac operator and prevents RNA polymerase from initiating transcription of the lactose utilization genes from the promoter. Therefore, in the absence of lactose, the lactose utilization genes are only expressed at a very low basal level (see Figure 2A). This low level of expression allows synthesis of a few lactose permease molecules, which permit the entry of lactose into the cell when lactose is present, and a few β-galactosidase molecules, which metabolize lactose or convert it to allolactose.

Allolactose is the inducer of the lac operon, acting as a signal that lactose is present. Allolactose binds to the repressor protein, changing its shape in such a way that the repressor can no longer bind to the operator. This allows RNA polymerase to effectively initiate transcription from the lac promoter (see Figure 2B).

Transcription of an operon generates an mRNA transcript of all the genes contained within the operon. Ribosomes can translate this single mRNA to generate several distinct proteins. In the case of the lac operon, transcription produces an mRNA molecule that is translated by ribosomes to generate β-galactosidase, lactose permease, and thiogalactoside acetyltransferase. Messenger RNA molecules that encode more than one gene are called polycistronic mRNAs. The common regulation mechanism determines when each polycistronic mRNA is synthesized. This is the main means by which operons commonly regulate the expression of one or more functionally regulated genes.

Bibliography

Hartwell, Leland, et al. Genetics: From Genes to Genomes. Berkeley: McGraw-Hill, 2000.

Miller, Jeffrey H., and Reznikoff, William S., eds. Operon, 2nd ed. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1980.

—Michael Buratovich

An operon is a segment of DNA containing all genes used to produce proteins in a specific metabolic pathway. A functional operon also contains the RNA polymerase-binding site known as a promoter as well as an on-off switch known as the operator. So far, operons have been identified only in bacteria, as this highly efficient grouping of related genes maximizes the information encoded on their single chromosome.

A segment of a chromosome comprising an operator gene and closely linked structural genes having related functions, the activity of the latter being controlled by the operator gene through its interaction with a regulator gene.

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (December 2007)

An operon is a functioning unit of key nucleotide sequences of DNA including an operator, a common promoter, and one or more structural genes, which is controlled as a unit to produce messenger RNA (mRNA), in the process of transcription by an RNA polymerase.

A typical operon.

Contents 1 History 2 Overview 3 The operon as a unit of transcription 4 Promoter 5 Operator 6 Operon gene regulation 7 The lac operon 8 The trp operon 9 Predicting the number and organization of operons 10 See also 11 References 12 External links

History

The term ‘‘operon’’ was first proposed in a short paper in the Proceedings of the French Academy of Science in 1960. From this paper, the so-called general theory of the operon was developed. This theory suggested that all genes are controlled by means of operons through a single feedback regulatory mechanism: repression. Later, it was discovered that the regulation of genes is a much more complicated process. Indeed, it is not possible to talk of a general regulatory mechanism, as there are many, and they vary from operon to operon. Despite modifications, the development of the operon concept is considered one of the landmark events in the history of molecular biology.

Overview

Operons occur primarily in prokaryotes but also in some eukaryotes, including nematodes. An operon is made up of several structural genes arranged under a common promoter and regulated by a common operator. It is a set of adjacent structural genes whose mRNA is synthesized in one piece, plus the adjacent regulatory signals that affect transcription of the structural genes.^5[1] The regulators of a given operon, including repressors, corepressors, and activators, are not necessarily coded for by that operon. The location and condition of the regulators, promoter, operator and structural DNA sequences can determine the effects of common mutations.

The first operon to be described was the lac-operon in Escherichia coli.^[2]

Operons are related to regulons and stimulons. Whereas operons contain a set of genes regulated by the same operator, regulons contain a set of genes under regulation by a single regulatory protein, and stimulons contain a set of genes under regulation by a single cell stimulus.

The operon as a unit of transcription

An operon contains one or more structural genes which are transcribed into one polycistronic mRNA: a single mRNA molecule that codes for more than one protein. Upstream of the structural genes lies a promoter sequence which provides a site for RNA polymerase to bind and initiate transcription. Close to the promoter lies a section of DNA called an operator. The operon may also contain regulatory genes such as a repressor gene which codes for a regulatory protein that binds to the operator and inhibits transcription. Regulatory genes need not be part of the operon itself, but may be located elsewhere in the genome. The repressor molecule will reach the operator to block the transcription of the structural genes.

Promoter

Main article: promoter.

A promoter is a DNA sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, which then initiates transcription. In RNA synthesis, promoters indicate which genes should be used for messenger RNA creation - and, by extension, control which proteins the cell manufactures.

Operator

An operator is a segment of DNA that a regulatory protein binds to. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon^[3]. A repressor or activator can bind to an operator.

Operon gene regulation

Control of an operon is a type of gene regulation that enables organisms to regulate the expression of various genes depending on environmental conditions. Operon regulation can be either negative or positive by induction or repression.^[3]

Negative control involves the binding of a repressor to the operator to prevent transcription.

• In negative inducible operons, a regulatory repressor protein is normally bound to the operator and it prevents the transcription of the genes on the operon. If an inducer molecule is present, it binds to the repressor and changes its conformation so that it is unable to bind to the operator. This allows for expression of the operon.

• In negative repressible operons, transcription of the operon normally takes place. Repressor proteins are produced by a regulator gene but they are unable to bind to the operator in their normal conformation. However certain molecules called corepressors are bound by the repressor protein, causing a conformational change to the active state. The activated repressor protein binds to the operator and prevents transcription.

Operons can also be positively controlled. With positive control, an activator protein stimulates transcription by binding to DNA (usually at a site other than the operator).

• In positive inducible operons, activator proteins are normally unable to bind to the pertinent DNA. When an Inducer is bound by the activator protein, it undergoes a change in conformation so that it can bind to the DNA and activate transcription.

• In positive repressible operons, the activator proteins are normally bound to the pertinent DNA segment. However, when a corepressor is bound by the activator, it is prevented from binding the DNA. This stops activation and of the system.

The lac operon

Main article: lac operon.

The lac operon of the model bacterium Escherichia coli was the first operon to be discovered and provides a typical example of operon function. It consists of three adjacent structural genes, a promoter, a terminator, and an operator. The lac operon is regulated by several factors including the availability of glucose and lactose. This is an example of the derepressible model.

The trp operon

Main article: trp operon.

Discovered in 1953 by Jacques Monod and colleagues, the trp operon in E. coli was the first repressible operon to be discovered. While the lac operon can be activated by a chemical (allolactose), the tryptophan (Trp) operon is inhibited by a chemical (tryptophan). This operon contains five structural genes: trp E, trp D, trp C, trp B, and trp A, which encodes tryptophan synthetase. It also contains a promoter which binds to RNA polymerase and an operator which blocks transcription when bound to the protein synthesized by the repressor gene (trp R) that binds to the operator. In the lac operon, lactose binds to the repressor protein and prevents it from repressing gene transcription, while in the trp operon, tryptophan binds to the repressor protein and enables it to repress gene transcription. Also unlike the lac operon, the trp operon contains a leader peptide and an attenuator sequence which allows for graded regulation.^[4] This is an example of the corepressible model.

Predicting the number and organization of operons

The number and organization of operons has been studied most critically in E. coli. As a result, predictions can be made based on an organism's genomic sequence.

One prediction method uses the intergenic distance between reading frames as a primary predictor of the number of operons in the genome. The separation merely changes the frame and guarantees that the read through is efficient. Longer stretches exist where operons start and stop, often up to 40-50 bases.^[5]

An alternative method to predict operons is based on finding gene clusters where gene order and orientation is conserved in two or more genomes.^[6]

Operon prediction is even more accurate if the functional class of the molecules is considered. Bacteria have clustered their reading frames into units, sequestered by co-involvement in protein complexes, common pathways, or shared substrates and transporters. Thus, accurate prediction would involve all of these data, a difficult task indeed.

Pascale Cossart published in 2009 the first full map of an operon, identifying the genetic switches that operate in Listeria under different conditions.^[7]

See also

• gene regulatory network
• TATA box
• L-arabinose operon
• Protein biosynthesis
• Genetic code
• Prokaryote

References

1. ^ Miller JH, Suzuki DT, Griffiths AJF, Lewontin RC, Wessler SR, Gelbart WM (2005). Introduction to genetic analysis (8th ed.). San Francisco: W.H. Freeman. pp. 740. ISBN 0-7167-4939-4. 
2. ^ Jacob, F; Perrin, D; Sanchez, C; Monod, J (Feb 1960). "Operon: a group of genes with the expression coordinated by an operator". Comptes rendus hebdomadaires des seances de l'Academie des sciences 250: 1727–9. ISSN 0001-4036. PMID 14406329.  edit
3. ^ ^{a b} Lewin, Benjamin (1990). Genes IV (4th ed.). Oxford [Oxfordshire]: Oxford University Press. pp. 243–58. ISBN 0-19-854267-4. 
4. ^ Cummings MS, Klug WS (2006). Concepts of genetics (8th ed.). Upper Saddle River, NJ: Pearson Education. pp. 394–402. ISBN 0-13-191833-8. 
5. ^ Salgado H, Moreno-Hagelsieb G, Smith TF, Collado-Vides J (Jun 2000). "Operons in Escherichia coli: genomic analyses and predictions". Proc Natl Acad Sci USA. 97 (12): 6652–7. doi:10.1073/pnas.110147297. PMID 10823905. PMC 18690. http://www.pnas.org/cgi/content/full/97/12/6652. 
6. ^ Ermolaeva MD, White O, Salzberg SL (Mar 2001). "Prediction of operons in microbial genomes". Nucleic Acids Res. 29 (5): 1216–21. doi:10.1093/nar/29.5.1216. PMID 11222772. PMC 29727. http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11222772. 
7. ^ Cossart P (May 2009). Nature (May 17, 1009): (in press). 

External links

• Mycobacterium tuberculosis H37Rv Operon Correlation Browser
• The Operon Concept: F.Jacob & J.Monad-1961

v • d • e Transcription (Prokaryotic, Eukaryotic) Promoter (Pribnow box, TATA box, BRE, CAAT box) - Operon (gal operon, lac operon, trp operon) - Terminator - Enhancer - Insulator - Repressor (lac repressor, trp repressor) - Silencer - Histone methylation

v • d • e Biochemistry: regulation of gene expression Downregulation/Upregulation - Enzyme induction and inhibition - Gene silencing (RNA interference) - Imprinting - Post-transcriptional modification - Posttranslational modification Prokaryotic: Operon (Lac operon, Trp operon) - Eukaryotic: Histone acetylation and deacetylation - DNA methylation

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)