Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [17]
Jacob did not have a particular plan for his research when he ascended into the attic, but he ended up studying two examples of one major biological puzzle: why genes sometimes make proteins and sometimes don’t. For several years, Jacob investigated prophages, the viruses that disappear into their E. coli host, only to reappear generations later. Working with Élie Wollman, Jacob demonstrated that prophages actually insert their genes into E. coli’s own DNA. They allowed prophage-infected bacteria to mate with uninfected ones and then spun them apart. If the microbes stopped mating too soon, they could not transfer the prophage. The experiments revealed that the prophage consistently inserts itself in one spot in E. coli’s chromosome. The virus’s genes are nestled in among those of its host, and yet they remain silent for generations.
E. coli offered Jacob another opportunity to study genes that sometimes make proteins and sometimes don’t. To eat a particular kind of sugar, E. coli needs to make the right enzymes. In order to eat lactose, the sugar in milk, E. coli needs an enzyme called beta-galactosidase, which can cut lactose into pieces. Jacob’s colleague at the Pasteur Institute, Jacques Monod, found that if he fed E. coli glucose—a much better source of energy for E. coli than lactose—it made only a tiny amount of beta-galactosidase. If he added lactose to the bacteria, it still didn’t make much of the enzyme. Only after the bacteria had eaten all the glucose did it start to produce beta-galactosidase in earnest.
No one at the time had a good explanation for how genes in E. coli or its prophages could be quiet one moment and busy the next. Many scientists had assumed that cells simply churned out a steady supply of all their proteins all the time. To explain E. coli’s reaction to lactose, they suggested that the microbe actually made a steady stream of beta-galactosidase. Only when E. coli came into contact with lactose did the enzymes change their shape so that they could begin to break the sugar down.
Jacob, Monod, and their colleagues at the Pasteur Institute began a series of experiments to figure out the truth. They isolated mutant E. coli that failed to eat lactose in interesting ways. One mutant could not digest lactose, despite having a normal gene for beta-galactosidase. The scientists realized that E. coli used more than one gene to eat lactose. One of those genes encoded a channel in the microbe’s membranes that could suck in the sugar.
Strangest of all the mutants Jacob and Monod discovered were ones that produced beta-galactosidase and permease all the time, regardless of whether there was any lactose to digest. The scientists reasoned that E. coli carries some other molecule that normally prevents the genes for beta-galactosidase and permease from becoming active. It became known as the repressor. But Jacob and his colleagues had not been able to say how the repressor keeps genes quiet.
In the darkness of the Paris movie theater, Jacob hit on an answer. The repressor is a protein that clamps on to E. coli’s DNA, blocking the production of proteins from the genes for beta-galactosidase and the other genes involved in feeding on lactose. A signal, like a switch on a circuit, causes the repressor to stop shutting down the genes.
Another similar repressor might keep the genes of prophages silent as well, Jacob thought. Perhaps these circuits are common in all living