An
operon is a functioning unit of key
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
sequences of
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
including an operator, a common
promoterIn genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
, and one or more
structural 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, which is controlled as a unit to produce messenger RNA (mRNA), in the process of
transcriptionTranscription, or RNA synthesis, is the process of creating an equivalent 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 in the presence of the correct enzymes...
by an RNA polymerase.
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
genesGênes is the name of a département of the First French Empire in present Italy. It was named after the city Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa. It was divided into the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
are controlled by means of operons through a single feedback regulatory mechanism:
repressionRepression may refer to:* Memory inhibition, the ability to filter irrelevant memories from attempts to recall* Political repression, the oppression or persecution of an individual or group for political reasons...
. 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
prokaryoteThe prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. They differ from the eukaryotes, which have a cell nucleus. Most are unicellular, but a few prokaryotes such as myxobacteria have multicellular stages in their life cycles...
s but also in some
eukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
s, including
nematodeThe "roundworms" or "nematodes" are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 80,000 have been described, of which over 15,000 are parasitic. It has been estimated that the total number of...
s. An operon is made up of several
structural 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 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 The regulators of a given operon, including
repressorA repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing the rate of transcription. This blocking of expression is called repression....
s,
corepressorA corepressor is a protein that decreases gene expression by binding to a transcription factor which contains a DNA binding domain. The corepressor is unable to bind DNA by itself. The corepressor can repress transcriptional initiation by recruiting histone deacetylases which catalyze the removal...
s, and
activatorAn 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.
The first operon to be described was the lac-operon in
Escherichia coli.
Operons are related to
regulonIn cell biology a regulon is a collection of genes under regulation by the same regulatory protein. This term is generally used for prokaryotic systems, for example quorum sensing in bacteria....
s and
stimulonIn 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. 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 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 which are transcribed into one polycistronic mRNA: a single mRNA molecule that codes for more than one
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
. Upstream of the structural genes lies a
promoterIn genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
sequence which provides a site for
RNA 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...
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
repressorA repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing the rate of transcription. This blocking of expression is called repression....
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
In genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
.
A
promoter is a
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
sequence that enables a
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
to be
transcribedTranscription, or RNA synthesis, is the process of creating an equivalent 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 in the presence of the correct enzymes...
. The promoter is recognized by
RNA 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.
Operator
An
operator is a segment of
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
that a regulatory protein binds to. It is classically defined in the
lac 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, a promoter, a terminator, and an operator. The lac operon is regulated by several factors including the availability...
as a segment between the promoter and the genes of the operon. A
repressorA repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing the rate of transcription. This blocking of expression is called repression....
or
activatorAn 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...
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.
Negative control involves the binding of a
repressorA repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing the rate of transcription. This blocking of expression is called repression....
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
In 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 gene
A regulator gene 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 Inducer
In 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 of the system.
The lac operon
- Main article: 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, a promoter, a terminator, and an operator. The lac operon is regulated by several factors including the availability...
.
The
lac operon of the
modelA model organism is a 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...
bacterium
Escherichia coliEscherichia coli , is a Gram negative bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E...
was the first operon to be discovered and provides a typical example of operon function. It consists of three adjacent
structural 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, a
promoterIn genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
, a
terminatorIn 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. The
lac operon is regulated by several factors including the availability of
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
and
lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
. This is an example of the
derepressibleIn 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:...
model.
The trp operon
- Main article: trp operon
Trp operon is an operon - a group of genes that are used, or transcribed, together - that codes for the components for production of tryptophan. The Trp operon is present in many bacteria, but was first characterized in Escherichia coli. This is the specific example we will discuss here. It is...
.
Discovered in 1953 by
Jacques MonodSee also Jacques-Louis Monod, French-born composer and cousin of Jacques Monod.Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965...
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 (
allolactoseAllolactose is a disaccharide similar to lactose. It consists of the monosaccharides β-D-galactose and β-D-glucose linked through a β1-6 glycosidic linkage.-External links:*...
), 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
attenuatorThe attenuator plays an important regulatory role in prokaryotic cells because of the absence of the nucleus in prokaryotic organisms. The attenuator refers to a specific regulatory sequence that, when transcribed into RNA, forms hairpin structures to stop translation when certain conditions are...
sequence which allows for graded regulation. This is an example of the
corepressibleA corepressor is a protein that decreases gene expression by binding to a transcription factor which contains a DNA binding domain. The corepressor is unable to bind DNA by itself. The corepressor can repress transcriptional initiation by recruiting histone deacetylases which catalyze the removal...
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 CossartPascale 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.Cossart's studies of the...
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 network
A gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell whichinteract with each other and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA...
- TATA box
The TATA box is a DNA sequence found in the promoter region of most genes in eukaryotes and Archaea...
- L-arabinose operon
The 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 biosynthesis
Protein synthesis is the process in which cells build 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 used as input to...
- Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells. A more precise term for the concept might be "genetic cipher". The code defines a mapping between tri-nucleotide sequences, called codons, and amino acids...
- Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. They differ from the eukaryotes, which have a cell nucleus. Most are unicellular, but a few prokaryotes such as myxobacteria have multicellular stages in their life cycles...
External links