Ingenetics, anoperon is a functioning unit ofDNA containing a cluster ofgenes under the control of a singlepromoter.[1] The genes aretranscribed together into anmRNA strand and eithertranslated together in the cytoplasm, or undergosplicing to createmonocistronic mRNAs that are translated separately, i.e. several strands of mRNA that each encode a single gene product. The result of this is that the genes contained in the operon are eitherexpressed together or not at all. Several genes must beco-transcribed to define an operon.[2]
Originally, operons were thought to exist solely inprokaryotes (which includesorganelles likeplastids that are derived frombacteria), but their discovery ineukaryotes was shown in the early 1990s, and are considered to be rare.[3][4][5][6] In general, expression of prokaryotic operons leads to the generation ofpolycistronic mRNAs, while eukaryotic operons lead to monocistronic mRNAs.
Operons are also found in viruses such asbacteriophages.[7][8] For example,T7 phages have two operons. The first operon codes for various products, including a specialT7 RNA polymerase which can bind to and transcribe the second operon. The second operon includes alysis gene meant to cause the host cell to burst.[9]
The term "operon" was first proposed in a short paper in the Proceedings of theFrench Academy of Sciences in 1960.[10] From this paper, the so-called general theory of the operon was developed. This theory suggested that in all cases, genes within an operon are negatively controlled by arepressor acting at a singleoperator located before the first gene. Later, it was discovered that genes could be positively regulated and also regulated at steps that follow transcription initiation. Therefore, it is not possible to talk of a general regulatory mechanism, because different operons have different mechanisms. Today, the operon is simply defined as a cluster of genes transcribed into a single mRNA molecule. Nevertheless, the development of the concept is considered a landmark event in the history of molecular biology. The first operon to be described was thelac operon inE. coli.[10] The 1965Nobel Prize in Physiology and Medicine was awarded toFrançois Jacob,André Michel Lwoff andJacques Monod for their discoveries concerning the operon and virus synthesis.
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Operons occur primarily inprokaryotes but also rarely in someeukaryotes, includingnematodes such asC. elegans and the fruit fly,Drosophila melanogaster.[3]rRNA genes often exist in operons that have been found in a range of eukaryotes includingchordates. An operon is made up of severalstructural genes arranged under a commonpromoter and regulated by a common operator. It is defined as a set of adjacent structural genes, plus the adjacent regulatory signals that affect transcription of the structural genes.5[12] The regulators of a given operon, includingrepressors,corepressors, andactivators, 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.
Operons are related toregulons,stimulons andmodulons; 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. According to its authors, the term "operon" is derived from the verb "to operate".[13]
An operon contains one or morestructural genes which are generally transcribed into onepolycistronicmRNA (a single mRNA molecule that codes for more than oneprotein). However, the definition of an operon does not require the mRNA to be polycistronic, though in practice, it usually is.[6] Upstream of the structural genes lies apromoter sequence which provides a site forRNA polymerase to bind and initiate transcription. Close to the promoter lies a section of DNA called anoperator.
All thestructural genes of an operon are turned ON or OFF together, due to a single promoter and operator upstream to them, but sometimes more control over the gene expression is needed. To achieve this aspect, some bacterial genes are located near together, but there is a specific promoter for each of them; this is calledgene clustering. Usually these genes encode proteins which will work together in the same pathway, such as a metabolic pathway. Gene clustering helps a prokaryotic cell to produce metabolic enzymes in a correct order.[14]In one study, it has been posited that in theAsgard (archaea), ribosomal protein coding genes occur in clusters that are less conserved in their organization than in otherArchaea; the closer anAsgard (archaea) is to theeukaryotes, the more dispersed is the arrangement of the ribosomal protein coding genes.[15]
An operon is made up of 3 basic DNA components:
Not always included within the operon, but important in its function is aregulatory gene, a constantly expressed gene which codes forrepressor proteins. The regulatory gene does not need to be in, adjacent to, or even near the operon to control it.[17]
Aninducer (small molecule) can displace a repressor (protein) from the operator site (DNA), resulting in an uninhibited operon.
Alternatively, acorepressor can bind to the repressor to allow its binding to the operator site. A good example of this type of regulation is seen for thetrp operon.
Control of an operon is a type ofgene 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.[16]
Negative control involves the binding of arepressor to the operator to prevent transcription.
Operons can also be positively controlled. With positive control, anactivator protein stimulates transcription by binding to DNA (usually at a site other than the operator).
Thelac operon of themodel bacteriumEscherichia coli was the first operon to be discovered and provides a typical example of operon function. It consists of three adjacentstructural genes, apromoter, aterminator, and anoperator. Thelac operon is regulated by several factors including the availability ofglucose andlactose. It can be activated byallolactose. Lactose binds to the repressor protein and prevents it from repressing gene transcription. This is an example of thederepressible (from above: negative inducible) model. So it is a negative inducible operon induced by presence of lactose or allolactose.
Discovered in 1953 byJacques Monod and colleagues, the trp operon inE. 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 encodestryptophan 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 anattenuator sequence which allows for graded regulation.[18] This is an example of thecorepressible model.
The number and organization of operons has been studied most critically inE. 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.[19]
An alternative method to predict operons is based on finding gene clusters where gene order and orientation is conserved in two or more genomes.[20]
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's laboratory was the first to experimentally identify all operons of a microorganism,Listeria monocytogenes. The 517 polycistronic operons are listed in a 2009 study describing the global changes in transcription that occur inL. monocytogenes under different conditions.[21]
