Operon – Structure, Regulation, Types, and Functions

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Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus).

What is Operon?

• An operon is a functional unit of DNA comprising a cluster of genes controlled by a single promoter in genetics.

• An operon is a genetic regulatory system seen mostly in bacteria and their bacteriophages in which numerous genes are transcribed from a single promoter into a single RNA; these genes are frequently governed by particular regulatory signals and regulated by a common operator.

• Frequently, genes in an operon code for proteins engaged in a single metabolic pathway or the creation of structural components.

• The lac operon in Escherichia coli was the first operon to be described.

• Francois Jacob, André Michel Lwoff, and Jacques Monod were awarded the 1965 Nobel Prize in Physiology or Medicine for their discoveries about the structure of operons and other studies.

• In the early 1990s, the first operons in eukaryotes were reported; since then, they have been described in worms (such as Caenorhabditis elegans) and flies (e.g., Drosophila melanogaster).

• Operons are found mostly in prokaryotes, but also in some eukaryotes, including nematodes like C. elegans and Drosophila melanogaster.

• rRNA genes are frequently found in operons in a variety of eukaryotes, including chordates.

• Multiple structural genes organised under a shared promoter and regulated by a common operator compose an operon.

• It is characterised as a collection of nearby structural genes and adjacent regulatory signals that control the transcription of the structural genes.

• Regulators of a specific operon, such as repressors, corepressors, and activators, are not necessarily encoded by that operon.

• Operons are related to regulons, stimulants, and modules; whereas operons contain a collection of genes regulated by the same operator, regulons contain a collection of genes regulated by a single regulatory protein, and stimulants contain a collection of genes regulated by a single cell stimulus.

• An operon comprises multiple structural genes that are typically translated into a single polycistronic mRNA (a single mRNA molecule that codes for more than one protein).

• However, the definition of an operon does not need the mRNA to be polycistronic, despite the fact that this is typically the case in practise. A promoter sequence provides a location for RNA polymerase to bind and activate transcription upstream of structural genes. In close proximity to the promoter is a DNA segment known as the operator.

General structure of Operon

An operon is composed of three fundamental DNA components:

An operon is a complete package for gene expression and synthesis of polypeptides. By combining the related genes, all polypeptides required for a specific function are synthesized in response to a single stimulus. For example, the bacterium Escherichia coli contains a number of genes clustered into operons and regulons: the Lac operon which is involved in lactose degradation, the Trp operon which is involved in tryptophan biosynthesis, and the His operon which is involved in histidine biosynthesis. These operons are turned on when the gene products are needed.

• Promoter – A nucleotide sequence that permits transcription of a gene. RNA polymerase recognises the promoter and then commences transcription. In RNA synthesis, promoters signal which genes are to be used for messenger RNA synthesis and, by extension, determine which proteins are produced by the cell.

• Operator – The DNA sequence to which a repressor attaches. It is traditionally defined as the region between the promoter and the genes of the lac operon. Two further operators, O2 and O3, are situated at -82 and +413, respectively, in the lac operon. In the case of a repressor, the repressor protein prevents RNA polymerase from transcribing genes.

• Structural genes – The primary architectures of enzyme proteins involved in a metabolic pathway, such as amino acid production, are encoded by DNA.

A regulatory gene, a continually expressed gene that codes for repressor proteins, is not usually present in the operon but is essential to its function. The regulatory gene is not required to be within, adjacent to, or even close to the operon in order to regulate it. An inducer (small chemical) can displace a repressor (protein) from an operator site (DNA), resulting in an operon that is no longer repressed. Alternativamente, a corepressor can bind to the repressor to permit its binding to the operator site. The trp operon is an excellent example of this kind of control.

Regulation of Operon

The control of an operon is a form of gene regulation that enables organisms to regulate the expression of different genes in response to environmental factors. Negative or positive control of opéron can occur via induction or repression.

Negative control of Operon

• Negative control entails the binding of a repressor to the operator in order to inhibit transcription.

• Typically, in negatively inducible operons, a regulatory repressor protein is linked to the operator, preventing transcription of the genes on the operon. If an inducer molecule is present, it attaches to the repressor and modifies its conformation, preventing it from binding to the operator. This allows the operon to be expressed. The lac operon is a negatively regulated inducible operon, with allolactose as the inducer molecule.

• In operons that are negatively repressible, transcription occurs normally. A regulator gene produces repressor proteins, but they cannot bind to the operator in their normal configuration. However, the repressor protein binds particular molecules known as corepressors, producing a conformational shift at the active site. The active repressor protein inhibits transcription by binding to the operator. The trp operon, which is involved in the manufacture of tryptophan (which acts as its own corepressor), is a negatively regulated, repressible operon.

Positive control of Operon

• Operons can also be controlled positively. By attaching to DNA under positive control, an activator protein induces transcription (usually at a site other than the operator).

• Activator proteins in positive inducible operons are typically incapable of binding to the relevant DNA. When an inducer is coupled to an activator protein, it undergoes a conformational shift that allows it to bind to DNA and initiate transcription.

• In ordinarily repressible positive operons, activator proteins are coupled to the relevant DNA sequence. When an inhibitor is attached to an activator, however, it is inhibited from binding to DNA. This inhibits system activation and transcription.

Types of Operon

There are present two different types of operon such as;

1. Lac Operon

• The Lac operon is the prototypical example of an operon, and it degrades the milk protein lactose.

• The Lac operon is an inducible operon whose operator is inhibited by a repressor protein in the absence of lactose.

• The operon consists of a promoter and operator, as well as three genes (lacZ, lacY, and lacA) that code for -galactosidase, permease, and transacetylase, respectively.

• -galactosidase breaks down lactose into glucose and galactose, while the other two proteins assist in the metabolic process.

• The Lac operon is regulated by the regulatory gene lacI, which is situated right adjacent to the promoter region.

• LacI encodes an allosteric repressor protein that maintains the “off” state of the Lac operon.

• In order for the Lac operon to be activated, the repressor protein must be deactivated by an inducer molecule.

• In this system, the inducer molecule is allolactose, an isomer of lactose. Allolactose binds to allosteric sites on the repressor protein when lactose and its isomer are present in the cell, altering its conformation and rendering it inactive.

• Upon detachment of the repressor protein from the operator, RNA polymerase may bind to the promoter, transcription can occur, and the three lactose degradation genes can be produced.

• Lac is also subject to positive gene regulation. Even though the elimination of the repressor protein in the presence of lactose is necessary for the production of lacZ, lacY, and lacA genes, gene expression will remain low.

• The level of gene expression is determined by the amount of glucose, the cell’s primary energy source. Catabolite activation protein, an allosteric regulatory protein, regulates this regulation (CAP).

• When glucose levels in a cell are low, there is a high concentration of the chemical compound cyclic AMP. By connecting to the allosteric sites, cyclic AMP activates CAP, prompting it to attach to the Lac operon promoter.

• Contrary to the effect of repressor proteins, the binding of CAP to the Lac operon increases gene expression.

• When glucose levels in a cell increase, cyclic AMP levels decrease, and the activator protein dissociates from the promoter. If the repressor protein reattaches, transcription will revert to a low level or cease.

2. Trp Operon

• The trp operon in E. coli was the first repressible operon to be found. It was found in 1953 by Jacques Monod and his team.

• While a chemical (allolactose) can turn on the lac operon, the same chemical can turn off the tryptophan (Trp) operon (tryptophan).

• When trytophan is not available in the environment, the Trp operon makes it.

• The Trp operon is made up of a promoter, an operator, and five tryptophan-making genes (trp E, trp D, trp C, trp B, and trp A).

• The regulatory gene trpR, which is located far away from the Trp operon, controls the Trp operon.

• A repressible operon is the Trp operon, which is on unless a repressor protein turns it off.

• trpR is what makes the repressor protein. The repressor protein is always in the cell, but it is made in a form that doesn’t work.

• When a corepressor is present, in this case tryptophan, it binds to the repressor protein at an allosteric site. This makes the protein change its shape so that it can bind to the operator and stop transcription by stopping RNA polymerase from binding to the promoter. This saves energy for the cell because it doesn’t have to make tryptophan when it’s already there.

Operon Function

• An operon is a group of genes that work together to make polypeptides. By putting together the genes that are related, all of the polypeptides needed for a certain function can be made in response to a single stimulus. For example, the bacterium Escherichia coli has a number of genes that are grouped together into operons and regulons. The Lac operon helps break down lactose, the Trp operon helps make tryptophan, and the His operon helps make histidine. The gene products are made when these operons are turned on.

• Operons can be controlled in either a positive or negative way. Negative control is when an operon is turned off when a repressor is present. This can be repressible or inducible.

• A repressible operon is one that is usually on but can be turned off with the help of a molecule called a repressor.

• The repressor binds to the operator in a way that stops RNA polymerase from moving or binding so that transcription can’t happen. An operon that can be turned on only when needed is called “inducible.”

• If there is no inducer, the operator is blocked by a molecule called a repressor. When the inducer is there, it interacts with the repressor protein. This frees the repressor protein from the operator and lets transcription continue.

• Most of the time, inducible operons are involved in catabolic pathways, or the breaking down of a nutrient, while repressible operons are usually involved in anabolic pathways, or the making of an important part.

• When a regulatory protein is present, it makes gene expression go up. This is called “positive control” of an operon.

References

Ramos, J. L., García-Salamanca, A., Molina-Santiago, C., & Udaondo, Z. (2013). Operon. Brenner’s Encyclopedia of Genetics, 176–180. doi:10.1016/b978-0-12-374984-0.01096-2

Picknett, T. M., & Brenner, S. (2001). Operon. Encyclopedia of Genetics, 1377. doi:10.1006/rwgn.2001.0936

Osbourn AE, Field B. Operons. Cell Mol Life Sci. 2009 Dec;66(23):3755-75. doi: 10.1007/s00018-009-0114-3. Epub 2009 Aug 7. PMID: 19662496; PMCID: PMC2776167.