OPERON: DISCOVERY, MODEL, CLASSIFICATION, EXAMPLES - BIOLOGY - 2025

An operon consists of a group of sequentially ordered genes that regulate each other, that encode proteins that are functionally related, and that are found throughout the genome of bacteria and "ancestral" genomes.

This regulatory mechanism was described by F. Jacob and J. Monod in 1961, a fact that earned them the Nobel Prize in Physiology and Medicine in 1965. These researchers proposed and demonstrated the operation of operons through the genes that code for the enzymes required by Escherichia coli for the utilization of lactose.

Graphic diagram of a DNA strand with the genes that comprise the lactose operon (Promoter, Operator, lacZ, lacY, lacA and terminator) (Source: Llull ~ commonswiki Via Wikimedia Commons)

The operons are responsible for coordinating protein synthesis according to the needs of each cell, that is, they are only expressed to generate proteins at the time and in the exact place where they are required.

The genes contained within operons are generally structural genes, which means that they code for important enzymes that are directly involved in metabolic pathways within the cell. These can be the synthesis of amino acids, energy in the form of ATP, carbohydrates, etc.

Operons are also commonly found in eukaryotic organisms, however, in contrast to prokaryotic organisms, in eukaryotes the region of the operon is not transcribed as a single messenger RNA molecule.

Discovery

The first important advance regarding operons made by François Jacob and Jacques Monod was to address the problem of "enzymatic adaptation", which consisted in the appearance of a specific enzyme only when the cell was in the presence of a substrate.

Such a response of cells to substrates had been observed in bacteria for many years. However, the researchers wondered how the cell determined exactly which enzyme it had to synthesize in order to metabolize that substrate.

Jacob and Monod observed that bacterial cells, in the presence of galactose-like carbohydrates, produced 100 times more β-galactosidase than under normal conditions. This enzyme is responsible for breaking down the β-galactosides so that the cell uses them metabolically.

Therefore, both researchers called galactoside-type carbohydrates as "inducers", since they were responsible for inducing an increase in the synthesis of β-galactosidase.

Likewise, Jacob and Monod found a genetic region with three genes that were controlled in a coordinated way: the Z gene, coding for the enzyme β-galactosidase; the Y gene, coding for the enzyme lactose permease (transport of galactosides); and gene A, which codes for the enzyme transacetylase, which is also essential for the assimilation of galactosides.

Through subsequent genetic analyzes, Jacob and Monod clarified all aspects of the genetic control of the lactose operon, concluding that the segment of genes Z, Y and A constitutes a single genetic unit with coordinated expression, which was what they defined as "operon".

Operon model

The operon model was first accurately described in 1965 by Jacob and Monod to explain the regulation of genes that are transcribed and translated for the enzymes required in Escherichia coli in order to metabolize lactose as an energy source..

These researchers proposed that the transcripts of the gene or of the set of genes that are located consecutively are regulated by two elements: 1) a regulatory gene or repressor gene 2) and an operator gene or operator sequence.

The operator gene is always located next to the structural gene (s) whose expression it is responsible for regulating, while the repressor gene codes for a protein called “repressor” that binds to the operator and prevents its transcription.

Transcription is repressed when the repressor is linked to the operator gene. In this way, the genetic expression of the genes that encode the enzymes necessary to assimilate lactose are not expressed and, therefore, it cannot metabolize said disaccharide.

Functional diagram of the lactose operon through its different control elements. This is the “model” operon used by biology teachers to teach the functioning of these genes (Source: Tereseik. Work derived from G3pro image. Spanish translation by Alejandro Porto. Via Wikimedia Commons)

At present it is known that the binding of the repressor to the operator prevents, with steric mechanisms, that the RNA polymerase binds to the promoter site so that it begins to transcribe genes.

The promoter site is the "site" that RNA polymerase recognizes to bind and transcribe genes. As it cannot bind, it cannot transcribe any of the genes in the sequence.

The operator gene lies between a genetic region of the sequence known as the promoter and the structural genes. However, Jacob and Monod did not identify this region in their time.

It is now known that the complete sequence that includes the structural gene or genes, the operator and the promoter, is in essence what constitutes an "operon".

Classification of operons

Operons are classified into only three different categories that depend on the way they are regulated, that is, some are expressed continuously (constitutive), others need some specific molecule or factor to activate (inducible) and others are expressed continuously until that the inducer is expressed (repressible).

The three types of operons are:

Inducible operon

Operons of this type are regulated by molecules in the environment such as amino acids, sugars, metabolites, etc. These molecules are known as inducers. If the molecule that acts as an inducer is not found, the genes of the operon are not actively transcribed.

In inducible operons, the free repressor binds to the operator and prevents transcription of the genes found in the operon. When the inducer binds to the repressor, a complex is formed that cannot bind to the repressor and thus the genes of the operon are translated.

Repressible Operon

These operons depend on specific molecules: amino acids, sugars, cofactors or transcription factors, among others. These are known as corepressors and act in a totally opposite way to inductors.

Only when the corepressor binds with the repressor does transcription stop and thus transcription of the genes contained within the operon does not occur. Then the transcription of a repressible operon only stops with the presence of the corepressor.

Constitutive operon

These types of operons are not regulated. They are constantly being actively transcribed and, in the event of any mutation affecting the sequence of these genes, the life of the cells that contain them can be affected and, in general, trigger programmed cell death.

Examples

The earliest and most widely recognized example of the function of an operon is the lac (lactose) operon. This system is responsible for transforming lactose, a disaccharide, into the monosaccharides glucose and galactose. Three enzymes act in this process:

- β-galactosidase, responsible for converting lactose into glucose and galactose.

- Lactose permease, responsible for transporting lactose from the extracellular medium to the interior of the cell and

- Transcetylase, which belongs to the system, but has an unknown function

The trp (tryptophan) operon from Escherichia coli controls tryptophan synthesis, having chorismic acid as its precursor. Within this operon are the genes for five proteins that are used for the production of three enzymes:

- The first enzyme, encoded by genes E and D, catalyzes the first two reactions of the tryptophan pathway and is known as anthranilate synthetase

- The second enzyme is glycerolphosphate and catalyzes the subsequent steps to anthranilate synthetase

- The third and last enzyme is tryptophan synthetase, responsible for producing tryptophan from indole-glycerol phosphate and serine (this enzyme is a product of genes B and A)

References

1. Blumenthal, T. (2004). Operons in eukaryotes. Briefings in Functional Genomics, 3 (3), 199-211.
2. Gardner, EJ, Simmons, MJ, Snustad, PD, & Santana Calderón, A. (2000). Principles of genetics. Principles of genetics.
3. Osbourn, AE, & Field, B. (2009). Operons. Cellular and molecular life sciences, 66 (23), 3755-3775.
4. Shapiro, J., Machattie, L., Eron, L., Ihler, G., Ippen, K., & Beckwith, J. (1969). Isolation of pure lac operon DNA. Nature, 224 (5221), 768-774.
5. Suzuki, DT, & Griffiths, AJ (1976). An introduction to genetic analysis. WH Freeman and Company.