Control of Gene Expression in Prokaryotes

In prokaryotes, genes that are functionally related are often grouped into a single unit called an operon, transcribed together under the control of one shared promoter. This concept comes from the Jacob-Monod model, the first major model of gene regulation, originally proposed in bacteria. Instead of giving every gene its own individual promoter — the eukaryotic strategy — bacteria group genes with related functions and control them with a shared regulatory system. That's more efficient, especially for responding quickly to environmental changes.

Key Takeaways

• An operon groups functionally related genes under one promoter, made up of a regulator gene, promoter, operator, and structural genes.

• Inducible systems (like the lac operon) are normally off; an inducer (allolactose) inactivates the repressor to turn transcription on — negative control.

• The lac operon also has positive control: CAP, activated by cAMP when glucose is low, boosts RNA polymerase binding.

• Repressible systems (like the trp operon) are normally on; a corepressor (tryptophan) activates the repressor to turn transcription off — an example of feedback inhibition.

• Inducible and repressible systems differ in default state and in whether their regulatory molecule turns the repressor off or on.

The Operon Model

Every operon is built from four key components:

From here, prokaryotic operons fall into two regulatory categories: inducible systems and repressible systems.

Inducible Systems

In an inducible system, the default state is off — the genes aren't expressed unless something specific turns them on.

Normally, a repressor protein is bound to the operator, physically blocking RNA polymerase from transcribing the structural genes. This is an example of negative control — gene expression is prevented by the presence of a repressor. When an inducer molecule is present, it binds the repressor protein, causing it to change shape and fall off the operator. Once the repressor is gone, RNA polymerase can move forward and begin transcription. The presence of the inducer is what turns the gene on.

The lac operon. A classic example of an inducible system is the lac operon, found in E. coli, which contains the genes needed to break down lactose.

• No lactose present: the lac repressor binds the operator, physically blocking RNA polymerase — there's no need to produce lactose-digesting enzymes if there's no lactose to digest.

• Lactose available: some of it is converted into allolactose, which acts as the inducer. Allolactose binds the repressor, causing it to change shape and fall off the operator. RNA polymerase can then proceed with transcription, and the cell begins making the enzymes needed to break down lactose.

Positive control: CAP and cAMP. The lac operon isn't only regulated by the repressor's negative control — it also has a positive control layer through catabolite activator protein (CAP). CAP only becomes active when glucose levels are low. When glucose is scarce, the signaling molecule cyclic AMP (cAMP) increases inside the cell; cAMP binds CAP, and the resulting CAP–cAMP complex binds a site near the promoter, making it easier for RNA polymerase to bind and initiate transcription.

So, to summarize: the lac operon is inducible — normally off, turning on in the presence of lactose — and it's controlled two ways: negative control through the lac repressor, and positive control through the CAP–cAMP complex, which boosts transcription specifically when glucose is low.

Repressible Systems

In a repressible system, the default state is on — the genes are usually being actively transcribed and expressed. Under certain conditions, though, the system can be shut off.

In the absence of a specific signal, the repressor protein is inactive and can't bind the operator, so RNA polymerase is free to transcribe the structural genes. But when a specific molecule called a corepressor is present, it binds the repressor protein and activates it. Once activated, the repressor binds the operator, blocks RNA polymerase, and shuts off transcription.

The trp operon. A good example of a repressible system is the trp operon, responsible for synthesizing the amino acid tryptophan.

• Tryptophan low: the repressor is inactive, transcription proceeds, and the enzymes for synthesizing tryptophan are made.

• Tryptophan abundant: tryptophan itself acts as the corepressor, binding and activating the trp repressor. The now-active repressor binds the operator, blocks transcription, and prevents further tryptophan production.

The presence of the pathway's own end product — tryptophan — is what shuts the pathway down. This is an example of feedback inhibition, which helps the cell conserve resources by not overproducing something it already has enough of.

Inducible vs. Repressible: Side-by-Side

Common MCAT Mistakes

• Mixing up default states. Inducible systems (lac) are normally off; repressible systems (trp) are normally on. Don't assume every operon starts in the same state.

• Confusing what the inducer and corepressor do to the repressor. An inducer (allolactose) inactivates the repressor and turns transcription on. A corepressor (tryptophan) activates the repressor and turns transcription off — the opposite effect.

• Forgetting the lac operon has two layers of control. Students often focus only on the lac repressor (negative control) and forget the CAP–cAMP system (positive control) that boosts transcription when glucose is low.

• Mislabeling CAP as a repressor. CAP is an activator, not a repressor — it makes it easier for RNA polymerase to bind, which is positive control, not negative control.

MCAT-Style Concept Check

Question: In the trp operon, what effect does binding of tryptophan (the corepressor) have on the trp repressor protein?

• A) It inactivates the repressor, allowing RNA polymerase to transcribe the structural genes.

• B) It activates the repressor, enabling it to bind the operator and block transcription.

• C) It binds directly to the operator, physically blocking RNA polymerase itself.

• D) It increases production of cAMP, which activates CAP to enhance transcription.

Answer: B

Explanation: The trp operon is a repressible system, normally on by default. Tryptophan acts as the corepressor: when it binds the trp repressor protein, it activates that repressor, allowing it to bind the operator and physically block RNA polymerase from transcribing the structural genes. This shuts down further tryptophan synthesis — an example of feedback inhibition. Option A describes an inducer's effect (like allolactose in the lac operon), not a corepressor's. Option C is incorrect because tryptophan binds the repressor protein, not the operator DNA directly. Option D describes the unrelated CAP–cAMP positive control system in the lac operon.

FAQ

What is an operon?

An operon is a cluster of functionally related genes in prokaryotes transcribed together under the control of one shared promoter. It's made up of a regulator gene, a promoter, an operator, and the structural genes themselves.

What's the difference between an inducible and a repressible operon?

An inducible operon (like the lac operon) is normally off and is turned on when an inducer molecule inactivates the repressor. A repressible operon (like the trp operon) is normally on and is turned off when a corepressor molecule activates the repressor.

What's the difference between negative and positive control in the lac operon?

Negative control comes from the lac repressor, which blocks transcription when bound to the operator. Positive control comes from the CAP–cAMP complex, which becomes active when glucose is low and helps RNA polymerase bind the promoter more effectively.

What is feedback inhibition, and how does the trp operon show it?

Feedback inhibition is when the end product of a pathway shuts down its own production. In the trp operon, abundant tryptophan acts as a corepressor that activates the trp repressor, blocking further transcription of the genes needed to make more tryptophan.