Operon - WikiHQ

thumb|350px|right|A typical operon

In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo 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 co-transcribed to define an operon.

Originally, operons were thought to exist solely in prokaryotes (which includes organelles like plastids that are derived from bacteria), but their discovery in eukaryotes was shown in the early 1990s, and are considered to be rare. In general, expression of prokaryotic operons leads to the generation of polycistronic mRNAs, while eukaryotic operons lead to monocistronic mRNAs.

Operons are also found in viruses such as bacteriophages. For example, T7 phages have two operons. The first operon codes for various products, including a special T7 RNA polymerase which can bind to and transcribe the second operon. The second operon includes a lysis gene whose function is 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 Sciences 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 in E. coli. 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" 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 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.

In one study, it has been posited that in the Asgard (archaea), ribosomal protein coding genes occur in clusters that are less conserved in their organization than in other Archaea; the closer an Asgard (archaea) is to the eukaryotes, the more dispersed is the arrangement of the ribosomal protein coding genes.

General structure

[[File:Lac Operon.svg|thumb|300px|1: RNA Polymerase, 2: Repressor, 3: Promoter, 4: Operator, 5: Lactose, 6: lacZ, 7: lacY, 8: lacA.

Top: The gene is essentially turned off. There is no lactose to inhibit the repressor, so the repressor binds to the operator, which obstructs the RNA polymerase from binding to the promoter and making lactase.

Bottom: The gene is turned on. Lactose is inhibiting the repressor, allowing the RNA polymerase to bind with the promoter, and express the genes, which synthesize lactase. Eventually, the lactase will digest all of the lactose, until there is none to bind to the repressor. The repressor will then bind to the operator, stopping the manufacture of lactase.]]

An operon is made up of 3 basic DNA components:

Promoter – a nucleotide sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, 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 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 constantly expressed gene which codes for repressor proteins. The regulatory gene does not need to be in, adjacent to, or even near the operon to control it.

An inducer (small molecule) can displace a repressor (protein) from the operator site (DNA), resulting in an uninhibited operon.

Alternatively, a corepressor 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.

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. 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'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 in L. monocytogenes under different conditions.

Operons response to genome-wide stresses

Primary promoters are the main controllers of operons. However, many operons have internal promoters. For example, half of all operons of E. coli have internal promoters. What happens when both the primary as well as the internal promoters are simultaneously perturbed? A recent study followed how each gene in each operon responded to such genome-wide stresses. They found that many transcription events of operons end prematurely in those conditions. They also found that internal promoters compensate significantly for those terminations creating a wave-like response pattern along operons. Next, it was shown that the same occurs in evolutionarily distant bacteria, such as Bacillus subtilis, Corynebacterium glutamicum, and Helicobacter pylori.

References

External links

Mycobacterium tuberculosis H37Rv Operon Correlation Browser
OBD - Operon database (a bit awkward to use though)