Control of Gene Expression

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Control of Gene Expression

Gene Regulation Is Necessary

~ 42 000 genes exist that code for proteins in humans, but not all proteins are required at all times.

By switching genes off when they are not needed, cells can prevent resources from being wasted. There should be natural selection favouring the ability to switch genes on and off.

A typical human cell normally expresses about 3% to 5% of its genes at any given time.

Housekeeping genes are genes that are switched on all the time because they are needed for vital functions

Gene expression in eukaryotes is controlled by a variety of mechanisms that range from those that prevent transcription to those that prevent expression after the protein has been produced. The various mechanisms can be placed into one of these four categories: transcriptional, posttranscriptional, translational, and posttranslational.

Prokaryotes

Much of our understanding of gene control comes from studies of prokaryotes.

Prokaryotes have two levels of gene control. Transcriptional and translational.

Operons

Operons are groups of genes that function to produce proteins needed by the cell.

Prokaryotic cells use operons to regulate genes and their respective proteins.

Operons are made up of:

1.

Structural Genes – code for the proteins needed. Ex: the proteins needed to breakdown sugar

2.

Promoter – are where RNA polymerase binds to the DNA

3.

Operator – a short sequence of bases between structural genes and a promoter.

Note: the promoter and operator regions have a small area of overlap

The lac operon

Lactose is a sugar found in milk. If lactose is present, E. coli (the common intestinal bacterium) needs to produce the necessary enzymes to digest it. Three different enzymes are needed.

In the diagrams below, lacZ, lacY and lacA represent the genes whose products are necessary to digest lactose. In the normal condition, the genes do not function because a repressor protein (LacI) is active and bound to the DNA preventing transcription. When the repressor protein is bound to the DNA, RNA polymerase cannot bind to the DNA. The protein must be removed before the genes can be transcribed.

When lactose is present, it binds directly to the LacI protein and therefore

“removes the roadblock”. For this reason, lactose is known as a signal molecule or inducer. Transcription of the three genes can now proceed.

a) When lactose is not present in the cell environment, the LacI protein binds to the lac operator, covering part of the promoter and thereby, blocking transcription b) Lactose binds to the LacI protein, changing its shape. It can no longer bind to the lac operator and transcription proceeds

The lac operon is an example of an inducible operon because the structural genes are normally inactive. They are activated when lactose is present.

The trp Operon

Repressible operons are the opposite of inducible operons. Transcription occurs continuously and the repressor protein must be activated to stop transcription.

Tryptophan is an amino acid needed by E. coli for the production of protein and the genes that code for proteins that produce tryptophan are continuously transcribed as shown below. E. coli bacteria are capable of making their own tryptophan. If there is a high concentration of tryptophan present in the intestinal environment, the E. coli no longer needs to produce their own, and transcription is stopped.

This operon contains five different genes that code for five polypeptides that make three enzymes. These three enzymes are needed to synthesize tryptophan. Since tryptophan and the active repressor are both needed to inactivate the trp operon, tryptophan is called a corepressor.

a) Lack of tryptophan inactivates the repressor and transcription proceeds b) Tryptophan acts as a corepressor and binds to the tryptophan repressor. The complex can now bind to the trp operator and transcription is blocked

The trp operon is an example of a repressible operon because the structural genes are active and are inactivated when tryptophan is present.

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