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In
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, an operon is a functioning unit of DNA containing a cluster of
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s under the control of a single promoter. The genes are transcribed together into an
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
strand and either
translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
together in the cytoplasm, or undergo splicing to create
monocistronic A cistron is an alternative term for "gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic. History The words ''cistron'' and ''gene ...
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 ''co-transcribed'' to define an operon. Originally, operons were thought to exist solely in
prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s (which includes
organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s like plastids that are derived from
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
), but since the discovery of the first operons in
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s in the early 1990s, more evidence has arisen to suggest they are more common than previously assumed. In general, expression of prokaryotic operons leads to the generation of
polycistronic A cistron is an alternative term for "gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic. History The words ''cistron'' and ''gene ...
mRNAs, while eukaryotic operons lead to monocistronic mRNAs. Operons are also found in viruses such as
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s. For example,
T7 phage Bacteriophage T7 (or the T7 phage) is a bacteriophage, a virus that infects bacteria. It infects most strains of ''Escherichia coli'' and relies on these hosts to propagate. Bacteriophage T7 has a lytic life cycle, meaning that it destroys th ...
s have two operons. The first operon codes for various products, including a special
T7 RNA polymerase T7 RNA Polymerase is an RNA polymerase from the T7 bacteriophage that catalyzes the formation of RNA from DNA in the 5'→ 3' direction. Activity T7 polymerase is extremely promoter-specific and transcribes only DNA downstream of a T7 promo ...
which can bind to and transcribe the second operon. The second operon includes a
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
gene meant to cause the host cell to burst.


History

The term "operon" was first proposed in a short paper in the Proceedings of the
French Academy of Science The French Academy of Sciences (French: ''Académie des sciences'') is a learned society, founded in 1666 by Louis XIV at the suggestion of Jean-Baptiste Colbert, to encourage and protect the spirit of French scientific research. It was at t ...
in 1960. 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 a repressor acting at a single operator 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 the
lac operon The ''lactose'' operon (''lac'' operon) is an operon required for the transport and metabolism of lactose in ''E. coli'' and many other enteric bacteria. Although glucose is the preferred carbon source for most bacteria, the ''lac'' operon allows ...
in '' E. coli''. The 1965
Nobel Prize in Physiology and Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
was awarded to
François Jacob François Jacob (17 June 1920 – 19 April 2013) was a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through regulation of transcription. He shared the 1965 Nobel Prize ...
,
André Michel Lwoff André Michel Lwoff (8 May 1902 – 30 September 1994) was a French microbiologist and Nobel laureate of Russian-Polish origin. Education, early life and career Lwoff was born in Ainay-le-Château, Allier, in Auvergne, France, the son of Marie ( ...
and
Jacques Monod Jacques Lucien Monod (February 9, 1910 – May 31, 1976) was a French biochemist who won the Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and André Lwoff "for their discoveries concerning genetic control of e ...
for their discoveries concerning the operon and virus synthesis.


Overview

Operons occur primarily in
prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s but also in some
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, including
nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
s such as ''C. elegans'' and the fruit fly, ''Drosophila melanogaster''.
rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...
genes often exist in operons that have been found in a range of eukaryotes including
chordate A chordate () is an animal of the phylum Chordata (). All chordates possess, at some point during their larval or adult stages, five synapomorphies, or primary physical characteristics, that distinguish them from all the other taxa. These fiv ...
s. 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 The regulators of a given operon, including repressors,
corepressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, ...
s, 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
regulon In molecular genetics, a regulon is a group of genes that are regulated as a unit, generally controlled by the same regulatory gene that expresses a protein acting as a repressor or activator. This terminology is generally, although not exclusiv ...
s, stimulons and
modulon In molecular genetics, a regulon is a group of genes that are gene regulation, regulated as a unit, generally controlled by the same regulatory gene that gene expression, expresses a protein acting as a repressor or activator (genetics), activator ...
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" is derived from the verb "to operate".


As a unit of transcription

An operon contains one or more structural genes which are generally transcribed into one
polycistronic A cistron is an alternative term for "gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic. History The words ''cistron'' and ''gene ...
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
(a single mRNA molecule that codes for more than one
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
). 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 In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
to bind and initiate transcription. Close to the promoter lies a section of DNA called an ''operator''.


Operons versus clustering of prokaryotic genes

All the structural 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 called gene 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.


General structure

An operon is made up of 3 basic DNA components: * Promoter – a
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
sequence that enables a gene to be transcribed. The promoter is recognized by
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
, 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 produces. * Operator – a segment of DNA to which a repressor binds. It is classically defined in the
lac operon The ''lactose'' operon (''lac'' operon) is an operon required for the transport and metabolism of lactose in ''E. coli'' and many other enteric bacteria. Although glucose is the preferred carbon source for most bacteria, the ''lac'' operon allows ...
as a segment between the promoter and the genes of the operon. The main operator (O1) in the ''lac'' operon is located slightly downstream of the promoter; two additional operators, O2 and O3 are located at -82 and +412, respectively. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from transcribing the genes. * Structural genes – the genes that are co-regulated by the operon. Not always included within the operon, but important in its function is a
regulatory gene A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. Regulatory sequences, which encode regulatory genes, are often at the five prime end (5') to the start site of transcript ...
, a constantly expressed gene which codes for
repressor proteins In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to th ...
. The regulatory gene does not need to be in, adjacent to, or even near the operon to control it. An
inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
(small molecule) can displace a repressor (protein) from the operator site (DNA), resulting in an uninhibited operon. Alternatively, a
corepressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, ...
can bind to the repressor to allow its binding to the operator site. A good example of this type of regulation is seen for the
trp operon The ''trp'' operon is a group of genes that are transcribed together, encoding the enzymes that produce the amino acid tryptophan in bacteria. The ''trp'' operon was first characterized in ''Escherichia coli,'' and it has since been discovered in ...
.


Regulation

Control of an operon is a type of
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...
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 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
inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
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. The ''lac'' operon is a negatively controlled inducible operon, where the inducer molecule is
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 the occasional transglycosylati ...
. * In ''negative repressible operons'', transcription of the operon normally takes place. Repressor proteins are produced by a
regulator gene A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. Regulatory sequences, which encode regulatory genes, are often at the five prime end (5') to the start site of transcrip ...
, 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 site. The activated repressor protein binds to the operator and prevents transcription. The ''trp'' operon, involved in the synthesis of
tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
(which itself acts as the corepressor), is a negatively controlled repressible operon. 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 regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
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 an inhibitor 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
model A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure. Models c ...
bacterium ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' 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 Terminator may refer to: Science and technology Genetics * Terminator (genetics), the end of a gene for transcription * Terminator technology, proposed methods for restricting the use of genetically modified plants by causing second generation s ...
, and an operator. The ''lac'' operon is regulated by several factors including the availability of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
and lactose. It can be activated by
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 the occasional transglycosylati ...
. Lactose binds to the repressor protein and prevents it from repressing gene transcription. This is an example of the derepressible (from above: negative inducible) model. So it is a negative inducible operon induced by presence of lactose or allolactose.


The ''trp'' operon

Discovered in 1953 by
Jacques Monod Jacques Lucien Monod (February 9, 1910 – May 31, 1976) was a French biochemist who won the Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and André Lwoff "for their discoveries concerning genetic control of e ...
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 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 the occasional transglycosylati ...
), 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. This is an example of the corepressible 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 (born 21 March 1948) is a French bacteriologist who is affiliated with the Pasteur Institute of Paris. She is the foremost authority on ''Listeria monocytogenes'', a deadly and common food-borne pathogen responsible for encephal ...
's laboratory was the first to experimentally identify all operons of a microorganism, ''
Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host' ...
''. The 517 polycistronic operons are listed in a 2009 study describing the global changes in transcription that occur in ''L. monocytogenes'' under different conditions.


See also

* Evolutionary developmental biology *
Genetic code The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
*
Gene regulatory network A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the fun ...
*
L-arabinose operon The L-arabinose operon, also called the ''ara'' or ''araBAD'' operon, is an operon required for the breakdown of the five-carbon sugar L-arabinose in ''Escherichia coli''. The L-arabinose operon contains three structural genes: ''araB'', ''araA'', ...
*
Protein biosynthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
*
TATA box In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has ...
*
Umu Chromotest For pharmacology and genetics, the Umu Chromotest, first developed and published by Oda et al., is a biological assay (bioassay) to assess the genotoxic potential of chemical compounds. It is based on the ability of DNA-damaging agents to induce ...


References


External links


''Mycobacterium tuberculosis'' H37Rv Operon Correlation Browser

OBD
- Operon database (a bit awkward to use though) {{Authority control Gene expression *