coli
begins producing lactose-digesting enzymes at top speed. If the repressor is an off switch, CRP is an on switch.
Jacob and his colleagues christened the lactose-digesting genes the
lac
operon,
operon
meaning a set of genes that are all regulated by the same switches. As Jacob suspected, operons represent a common theme in the way genes work. Hundreds of
E. coli’
s genes are arrayed in operons, each controlled by switches. Some operons carry several switches, all of which must be thrown for them to make proteins. A single protein may be able to trigger a cascade of genes, switching on genes for making more switches, allowing
E. coli
to make hundreds of new kinds of proteins.
On-off switches are everywhere in nature. Prophages remain dormant inside
E. coli
thanks to repressors that keep their genes shut down. Stress causes the repressors to fall off and the prophages to make new viruses. Operons can be found in other bacteria as well. In animals like ourselves, operons appear to be much less common. But even genes that do not sit next to each other on our genome can be switched on by the same master-control protein.
It is only through the switching on and off of genes that our cells can behave differently from one another, despite carrying an identical genome. They can form liver cells or spit out bone, catch light or feel heat. By learning how
E. coli
drinks milk, Jacob and his colleagues opened the way to understanding why we humans are more than just amoebas.
LIVING CIRCUITS
To an engineer, a circuit is an arrangement of wires, resistors, and other parts, all laid out to produce an output from an input. Circuits in a Geiger counter create a crackle when they detect radioactivity. A room is cast in darkness when a light switch is turned off. Genes operate according to a similar logic. A genetic circuit has its own inputs and outputs. The
lac
operon works only if it receives two inputs: a signal that
E. coli
has run out of glucose and another signal that there’s lactose to eat. Its output is the proteins
E. coli
needs to break down the lactose.
E. coli
has no wires that scientists can pull apart to learn how its circuits work. Instead, they must do experiments of the sort Jacob and Monod carried out. They observe how quickly the bacteria respond to their environment, how quickly they make a certain protein or clear another one away. Scientists combine the results of experiment after experiment into models, which they use to make predictions about how future experiments will turn out. The fundamental discoveries that Jacob, Monod, and others made about
E. coli
have led other scientists to pick apart the circuitry of other species, including us. But in the fifty years since Jacob squirmed in a cinema seat, scientists have continued to pay close attention to
E. coli.
They discovered intriguing patterns in
E. coli’
s circuitry, which they mapped out in more detail than in of any other species, and they’ve discovered that
E. coli’
s circuitry mimics the sort of circuitry you might find in digital cameras or satellite radios.
To prove that I’m not dabbling in idle metaphor, I want to probe the wiring of one of
E. coli’
s many circuits. This particular circuit controls the construction of
E. coli’
s flagella. It has taken the work of many scientists over many years to discover most of the genes that belong to this circuit. But in 2005, Uri Alon and his colleagues at the Weizmann Institute of Science in Rehovot, Israel, figured out what the circuit does. It acts as a noise filter.
Engineers use noise filters to block static in phone lines, blurring in images, and any other input that obscures a true signal. In the case of
E. coli,
the noise is made up of misleading cues about its environment. With the help of a noise filter it can pay attention only to the cues that matter. It’s important for
E. coli
to ignore noise when it builds a flagellum because the process is a lot like building a cathedral.
The
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