Operon
Encyclopedia
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, an operon is a functioning unit of genomic DNA containing a cluster of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s under the control of a single regulatory signal or promoter. The genes are transcribed
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
together into an mRNA strand and either translated
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
together in the cytoplasm, or undergo trans-splicing
Trans-splicing
Trans-splicing is a special form of RNA processing in eukaryotes where exons from two different primary RNA transcripts are joined end to end and ligated....
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
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
together or not at all. Several genes must be both co-transcribed and co-regulated to define an operon.
Originally, operons were thought to exist solely in prokaryotes, but since the discovery of the first operons in eukaryotes in the early 1990s, more evidence has arisen to suggest they are more common than previously assumed.
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– repressionRepressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
. 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
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...
in E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. The 1965 Nobel Prize in Physiology and Medicine was awarded to François Jacob
François Jacob
François Jacob is a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through feedback on transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.-Childhood and education:François Jacob is...
, André Michel Lwoff
André Michel Lwoff
André Michel Lwoff was a French microbiologist. He was born in Ainay-le-Château, Allier, in Auvergne, France. He joined the Institute Pasteur in Paris when he was 19 years old...
and Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
for their discoveries concerning the operon and virus synthesis.
Overview
Operons occur primarily in prokaryoteProkaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s but also in some eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, including nematode
Nematode
The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...
s such as C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
. , and Drosophila melanogaster flies
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
. rRNA genes often exist in operons that have been found in a range of eukaryotes including chordate
Chordate
Chordates are animals which are either vertebrates or one of several closely related invertebrates. They are united by having, for at least some period of their life cycle, a notochord, a hollow dorsal nerve cord, pharyngeal slits, an endostyle, and a post-anal tail...
s. An operon is made up of several structural gene
Structural gene
A structural gene is a gene that codes for any RNA or protein product other than a regulatory factor . It may code for a structural protein, an enzyme, or an RNA molecule not involved in regulation...
s arranged under a common promoter and regulated by a common operator
Operator (biology)
In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
. It is defined as a set of adjacent structural genes, plus the adjacent regulatory signals that affect transcription of the structural genes.5 The regulators of a given operon, including repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
s, corepressor
Corepressor (genetics)
In molecular genetics, a corepressor is a substance that inhibits the expression of genes. A corepressor downregulates the expression of genes not through direct interaction with a gene promoter , but rather indirectly through interaction with repressor proteins that in turn bind to the...
s, and activator
Activator (genetics)
An activator is a DNA-binding protein that regulates one or more genes by increasing the rate of transcription. The activator may increase transcription by virtue of a connected domain which assists in the formation of the RNA polymerase holoenzyme, or may operate through a coactivator. A...
s, 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 regulon
Regulon
In cell biology and genetics, a regulon is a collection of genes or operons under regulation by the same regulatory protein. This term is generally used for prokaryotic systems, for example quorum sensing in bacteria. It is a group of operons/genes spread around the chromosome but controlled by a...
s, stimulon
Stimulon
In cell biology a stimulon is a collection of genes under regulation by the same stimulus. This term is generally used for prokaryotic systems, for example quorum sensing in bacteria....
s and modulon
Modulon
An operon is a set of genes controlled by a single DNA binding protein. Multiple operons controlled by the same repressor are grouped together as a regulon....
s; 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".
As a unit of transcription
An operon contains one or more structural geneStructural gene
A structural gene is a gene that codes for any RNA or protein product other than a regulatory factor . It may code for a structural protein, an enzyme, or an RNA molecule not involved in regulation...
s which are generally transcribed into one polycistronic mRNA (a single mRNA molecule that codes for more than one protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
). However, the definition of an operon does not require the mRNA to be polycistronic, though in practice, it usually is . Upstream of the structural genes lies a promoter sequence which provides a site for RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
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
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
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.
Structure
This is the general structure of an operon:- Promoter – a nucleotideNucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequence that enables a gene to be transcribedTranscription (genetics)Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. The promoter is recognized by RNA polymeraseRNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
, 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. - OperatorOperator (biology)In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
– a segment of DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
that a regulator binds to. It is classically defined in the lac operonLac operonThe lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...
as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from transcribing the genes. - Structural geneStructural geneA structural gene is a gene that codes for any RNA or protein product other than a regulatory factor . It may code for a structural protein, an enzyme, or an RNA molecule not involved in regulation...
s – the genes that are co-regulated by the operon.
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.Negative control involves the binding of a repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
to the operator to prevent transcription.
- In negative inducible operons, a regulatory repressor protein is normally bound to the operator, which prevents the transcription of the genes on the operon. If an inducerInducerIn molecular biology, an inducer is a molecule that starts gene expression.For a gene to be expressed, its DNA sequence must be copied to make a smaller, mobile molecule called messenger RNA , which carries the instructions for making a protein to the site where the protein is manufactured...
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 geneRegulator geneA regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. A regulator gene may encode a protein, or it may work at the level of RNA, as in the case of genes encoding microRNAs....
, 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 inducerInducerIn molecular biology, an inducer is a molecule that starts gene expression.For a gene to be expressed, its DNA sequence must be copied to make a smaller, mobile molecule called messenger RNA , which carries the instructions for making a protein to the site where the protein is manufactured...
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 transcription of the system.
The lac operon
The lac operon of the modelModel organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
bacterium Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
was the first operon to be discovered and provides a typical example of operon function. It consists of three adjacent structural gene
Structural gene
A structural gene is a gene that codes for any RNA or protein product other than a regulatory factor . It may code for a structural protein, an enzyme, or an RNA molecule not involved in regulation...
s, a promoter, a terminator
Terminator (genetics)
In genetics, a terminator, or transcription terminator is a section of genetic sequence that marks the end of gene or operon on genomic DNA for transcription.In prokaryotes, two classes of transcription terminators are known:...
, and an operator
Operator (biology)
In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
. The lac operon is regulated by several factors including the availability of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
and lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
. This is an example of the derepressible
Derepression
In genetics and biochemistry, a repressor gene inhibits the activity of an operator gene. By inactivating the repressor, the operator gene becomes active again. This effect is called derepression.-Derepression of ALA synthase:...
(from above: negative inducible) model.
The trp operon
Discovered in 1953 by Jacques MonodJacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
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
Allolactose
Allolactose is a disaccharide similar to lactose. It consists of the monosaccharides D-galactose and D-glucose linked through a β1-6 glycosidic linkage instead of the β1-4 linkage of lactose. It may arise from by the occasional transglycosylation of lactose by β-galactosidase.It is an inducer of...
), 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
Attenuator (genetics)
Attenuation is a regulatory feature found throughout Archaea and Bacteria causing premature termination of transcription. Attenuators are 5'-cis acting regulatory regions which fold into one of two alternative RNA structures which determine the success of transcription...
sequence which allows for graded regulation. This is an example of the corepressible
Corepressor (genetics)
In molecular genetics, a corepressor is a substance that inhibits the expression of genes. A corepressor downregulates the expression of genes not through direct interaction with a gene promoter , but rather indirectly through interaction with repressor proteins that in turn bind to the...
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.
An alternative method to predict operons is based on finding gene clusters where gene order and orientation is conserved in two or more genomes.
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
Pascale Cossart
Pascale Cossart is an award-winning bacteriologist at the Pasteur Institute of Paris, and the foremost authority on Listeria monocytogenes, a deadly and common food-borne pathogen responsible for encephalitis, meningitis, bacteremia, gastroenteritis, and other diseases.- Biography :Cossart earned...
published in 2009 the first full map of an operon, identifying the genetic switches that operate in Listeria under different conditions.
See also
- gene regulatory networkGene regulatory networkA gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell whichinteract with each other indirectly and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA.In general, each mRNA molecule goes...
- TATA boxTATA boxThe TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
- L-arabinose operonL-arabinose operonThe L-arabinose operon of the model bacterium Escherichia coli has been a focus for research in molecular biology for over 40 years, and has been investigated extensively at the genetic, biochemical, physiological, and biophysical levels....
- Protein biosynthesisProtein biosynthesisProtein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
- Genetic codeGenetic codeThe genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....