In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter.[1][2] The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create monocistronic 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 either expressed together or not at all. Several genes must be both co-transcribed and co-regulated to define an operon.[3]
Originally, operons were thought to exist solely in prokaryotes, but since the discovery of the first operons in eukaryotes in the early 1990s,[4][5] more evidence has arisen to suggest they are more common than previously assumed.[6]
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The term "operon" was first proposed in a short paper in the Proceedings of the French Academy of Science in 1960 [7]. 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, because different operons have different mechanisms. Despite modifications, the development of the concept is considered a landmark event in the history of molecular biology. The first operon to be described was the lac operon in E. coli.[2] The 1965 Nobel Prize in Physiology and Medicine was awarded to François Jacob, André Michel Lwoff and Jacques Monod for their discoveries concerning the operon and virus synthesis.
Operons occur primarily in prokaryotes but also in some eukaryotes, including nematodes such as C. elegans. , and Drosophila melanogaster flies. rRNA genes often exist in operons that have been found in a range of eukaryotes including chordates. An operon is made up of several structural genes arranged under a common promoter 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[8] 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.
Operons are related to regulons, stimulons and modulons; 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" means "to operate"[9].
An operon contains one or more structural genes which are generally transcribed into one polycistronic mRNA (a single mRNA molecule that codes for more than one protein). However, the definition of an operon does not require the mRNA to be polycistronic, though in practice, it usually is[10] . 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.
This is the general structure of an operon:
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.[11]
Negative control involves the binding of a repressor to the operator to prevent 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).
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 (from above: negative inducible) model.
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.[12] This is an example of the corepressible model.
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.[13]
An alternative method to predict operons is based on finding gene clusters where gene order and orientation is conserved in two or more genomes.[14]
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.[15]
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