A Theory is "an explanation of some natural phenomenon(a) that can incorporate facts, laws, inferences, and tested hypotheses to provide a conceptual framework that, both explains existing observations, and predicts new ones that are also able to be tested.

“The whole of science is nothing more than a refinement of everyday thinking.”

- Albert Einstein

To emphasize this point, this lecture is going to begin to discuss some of the complexities of regulation in the central dogma: higher orders of control.

While regulation occurs at every level of the central dogma for each of the myriad numbers of genes in any organism, it is important -in order for us just to get a "hint" of the complexity of control within living organisms to appreciate regulation at just one level and in the simplest system, the bacterium, E. coli.

The first level of control can be understood by understanding how genes involved in the break down of an important secondary sugar called lactose is controlled in bacterial systems (such as like E. coli). This bacterium controls expression the three genes that give rise to three enzymes involved in the breakdown of this sugar by putting all three genes behind a single promoter. In so doing it controls transcription of all the associated genes that have been clustered together in the same region of the chromosome. Their synthesis, therefore, is said to be coordinated within a sequence of genes called an "operon".

Complete shut-down of transcription in prokaryotes can occur by placing an obstacle between the promoter and its structural genes; by introducing a new section of DNA called the operator.

If a specific protein, the"repressor",is able to bind to the operator, it creates an obstacle, binding and/or movement of the RNA polymerase is blocked from transcribing the structural genes.

But now the bacterium has to synthesize a gene that makes this specific repressor protein, so why not put that gene in the same area of the genome, close to the operon it's controlling.

But all this does is provide a system that is always "Turned OFF" as the repressor protein ALWAYS binds the "operator" and blocks transcription.

So, to make this system regulatable, you will need to modify the repressor protein which blocks transcription to be able to bind the operator most of the time, but sometimes come off the DNA and allw transcription to occur. This repressor protein, would need to be an allosteric protein and have TWO  binding sites: one for the operator and the other for the inducer, which changes the shape of the repressor protein and disallows its binding to the operator.

This is exactly what happens in prokaryotes.

Example:

We have looked at catabolism of sugars, and how -like ourselves- a lot of organisms preferentially thrive on a Glucose diet. E. coli, is one such bacterium that prefers glucose, but when glucose availability is low and other sugars - such as lactose- are in abundance, E. coli can use these other sugars... in this example lactose.

Lactose is a disaccharide containing galactose - linked to glucose.

Lactose is transported into the cell by a carrier protein (enzyme) called ß-galactoside permease, whereupon the lactose is hydrolyzed to glucose and galactose by the enzyme ß-galactosidase.

Another enzyme is needed to protect the cell from the side effects of too much ß-galactosidase enzyme activity. It is called thiogalactoside transacetylase.

So, because all these genes are involved in the same process (metabolism of lactose), all these genes are clustered together in the genome and are synthesized on the same RNA transcript in what is called the lac operon.

To conserve energy, not too surprisingly, when no lactose is present, levels of all three enzymes should be and are low.

It turns out that the molecule, Lactose itself is able to activate (induce) expression of the operon and express large amounts of all three enzymes.

Remember that repressor protein....

The repressor protein fro the lac operon is called the lac repressor, and is coded for by the regulatory gene, lacI.

The lacI gene just happens to be located near the lac structural genes. However, not all regulatory genes are near the operons that they control.

Regulatory genes like lacI have their own promoters. In this instance, the lacI gene is expressed constitutively (i.e., it is expressed is all the time).

    

The lac operon: default OFF....inducible in the presence of substrate.     

Such operator/repressor control systems are general themes in the regulation of gene expression, although they are not always controlled in the same way.

;