The Lac Operon: Everyone's heard of it, but do you know how it was discovered?
'If gene expression determines the function of a cell, it must be important to control that process?' Yes, very! Let me tell you about the PaJaMo experiment.
Although we knew that DNA was the genetic material in the 1950s, there were still major questions about how DNA coded for protein and how that process, known as gene expression, was regulated.
While these were major questions at the time, an equally nagging question was whether enzymes (proteins) performed a specific function or if they could rearrange themselves to perform multiple functions.
There was a long standing hypothesis that enzymes were like little swiss army knives.
And they could be coaxed by environmental conditions to rearrange themselves to do different jobs depending on what was needed at the time.
A competing hypothesis argued that enzymes performed very specific functions and that it was actually the regulation of gene expression that determined how organisms responded to changes in their surroundings.
It was hypothesized that they did this by expressing different enzymes depending on what the current conditions required.
To settle this debate, Arthur Pardee, Francois Jacob, and Jacques Monod teamed up to study how bacteria are able to live and grow in the presence of multiple sugar sources.
It was known that E. coli could grow in the presence of both lactose and glucose and early work from Jacob showed that the 'lac' region of the bacterial genome seemed to control how they processed sugar.
This appeared to be the ideal system to suss out whether enzymes adapted to their conditions or if new enzymes were created to deal with whatever sugar was present.
Pardee, Jacob, and Monod (PaJaMo!) devised a series of experiments using bacteria that had different mutations (or combinations) in lac which contains 3 important regions:
z - makes beta-galactosidase, the enzyme that turns lactose into glucose and galactose
y - beta-galactosidase permease, the protein that brings lactose into the bacteria
i - inducer, a regulatory region that controls the expression of z and y
The figure above shows what happens in E. coli in the presence or absence of lactose (inducer).
When lactose is present (black dots) the bacteria make a lot of beta-galactosidase enzyme, when lactose isn't present (open dots) they don't make the enzyme.
Further research showed that the 'i' region is actually bound by a repressor protein that prevents the expression of z and y, and it's the binding of lactose to the repressor that releases this block!
While seemingly simple, the PaJaMo experiment unveiled what we now call the 'lac operon.'
It provided our first evidence that enzymes perform a specific function and that gene expression can be regulated to determine which enzymes are active at any given time!
Brian Krueger