Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [25]
There’s much to be learned about E. coli by thinking of it as a machine with circuitry that follows the fundamental rules of engineering. But only up to a point. Two Boeing 777s that are in equally good working order should behave in precisely the same way. Yet if they were like E. coli, one might turn south when the other turned north.
The difference between E. coli and the planes lies in the stuff from which they are made. Unlike wires and transistors, E. coli’s molecules are floppy, twitchy, and unpredictable. They work in fits and starts. In a plane, electrons stream in a steady flow through its circuits, but the molecules in E. coli jostle and wander. When a gene switches on, E. coli does not produce a smoothly increasing supply of the corresponding protein. A single E. coli spurts out its proteins unpredictably. If its lac operon turns on, it may spit out six beta-galactosidase enzymes in the first hour, or none at all.
This burstiness helps turn genetically identical E. coli into a crowd of individuals. Michael Elowitz, a physicist at Cal Tech, made E. coli’s individuality visible in an elegant experiment. He and his colleagues added an extra gene to the lac operon, encoding a protein that gave off light. When he triggered the bacteria to turn on the operon, they began to make the glowing proteins. But instead of glowing steadily, they flickered. Each burst of fluorescent proteins gave off a pulse of light. Some bursts were big, and some were small. And when Elowitz took a snapshot of the colony, it was not a uniform sea of light. Some microbes were dark at that moment while others shone at full strength.
These noisy bursts can produce long-term differences between genetically identical bacteria. They turn out to be responsible for making some E. coli eager for lactose and others reluctant. If you could peer inside a reluctant E. coli, you would find a repressor clamped tightly to the lac operon. Lactose can sometimes seep through the microbe’s membrane, and it can even sometimes pry away the repressor. Once the lac operon is exposed, E. coli’s gene-reading enzymes can get to work very quickly. They make an RNA copy of the operon’s genes, which is taken up by a ribosome and turned into proteins, including a beta-galactosidase enzyme.
But each E. coli usually contains about three repressors. They spend most of their time sliding up and down the microbe’s DNA, searching for the lac operon. It takes only a few minutes for one of them to find it and shut down the production of beta-galactosidase. Only a tiny amount of beta-galactosidase gets made in those brief moments of liberty. And what few enzymes do get made are soon ripped apart by E. coli’s army of protein destroyers. Adding a little more lactose does not change the state of affairs. Too little of the sugar gets into the microbe to keep the repressors away from the lac operon for long. The microbe remains reluctant.
Keep increasing the lactose, however, and this reluctant microbe will suddenly turn eager. There’s a threshold beyond which it produces lots of beta-galactosidase. The secret to this reversal is one of the other genes in the lac operon. Along with beta-galactosidase, E. coli makes the protein permease, which sucks lactose molecules into the microbe. When a reluctant E. coli’s lac operon switches on briefly, some of these permeases get produced. They begin pumping more lactose into the microbe, and that extra lactose can pull away more repressors. The lac operon can turn on for longer periods before a repressor can shut it down again, and so it makes more proteins—both beta-galactosidase for digesting lactose and permease for pumping in more lactose. A positive feedback sets in: more permease leads to more lactose,