How Does a Cell Know Not to Make an Enzyme It Does Not Need? Ask the Food

Several genes whose products work together on the same job are placed next to each other on the chromosome and share a single control region at the front. Reading the whole group produces one long message covering all of them, which is then translated into the separate proteins. Because they share one switch, the whole set is turned on or off together, which is exactly what is wanted when the proteins are useless individually and only make sense as a complete pathway. The switch itself consists of a site where the reading machinery attaches and a site where a blocking protein can sit.

The logic is a simple mechanical arrangement:

• •A repressor protein binds the control region and blocks reading
• •So the genes are off by default
• •The substance to be processed binds that repressor and changes its shape
• •The changed repressor lets go of the DNA
• •Reading proceeds and the enzymes are made
• •When the substance is used up the repressor binds again and it stops

The mechanism was deduced from genetics before anybody could look at DNA directly, which is why the work is admired. Francois Jacob and Jacques Monod at the Pasteur Institute studied bacteria that produce enzymes for digesting lactose only when lactose is present, and by collecting mutants that had lost the regulation in different ways they reasoned out that there must be a separate gene making a diffusible blocking substance and a site on the DNA where it acts. They published the model in 1961 and it was confirmed afterwards in every particular. They shared a Nobel Prize in 1965 with Andre Lwoff.

Blocking by default is only one of the two arrangements and the opposite one is equally common. Some groups of genes are silent until an activating protein binds nearby and helps the reading machinery attach, so the substance in question switches them on by assisting rather than by removing an obstacle. Many real systems combine both, so a set of genes for digesting a secondary food source is held off while the preferred food is available and switched on only when the preferred one runs out and the secondary one is present, which is a logical AND built out of two independent proteins binding the same stretch of DNA.

The arrangement itself is largely a bacterial one and the idea it established is universal. Before this work, genes were understood as recipes and the question of what determines which recipes are used was open. The model answered it by showing that some genes exist to control others, that control operates through proteins binding specific DNA sequences, and that the environment reaches the genome through that binding. That framework underlies all of modern molecular biology, including how a single human genome produces hundreds of cell types. Complex organisms use dispersed control regions rather than grouped genes, which is a difference of architecture rather than of principle.

Grouping the genes for one pathway under a single control region means the whole set switches together, which suits proteins that are useless individually. A blocking protein sits on that region until the substance to be processed binds it and changes its shape, at which point reading proceeds. Jacob and Monod deduced the mechanism from mutants in 1961, before anybody could examine DNA directly.