Microcosm by Carl Zimmer Page A

microbe must switch on about fifty genes, which make tens of thousands of proteins. Those proteins must come together in a tightly choreographed assembly. First the motor must insert itself in the membranes. A syringe has to slide through the center of the motor, which then injects thousands of proteins into the growing tail. The proteins squirm through the hollow shaft and emerge to form its new tip. The process takes an hour or two, which for
E. coli
can mean several generations. A new microbe inherits a partially built tail and passes it on, still unfinished, to its descendants.
    By the time
E. coli
has finished building these flagella, the crisis may be long over. All that energy will have gone to waste. So
E. coli
keeps tabs on its surroundings, and if life does seem to be getting better, it stops building its flagella. The only problem with this strategy is that a sign of better times may actually be a fleeting mirage. If
E. coli
abandons its flagella when a single oxygen molecule drifts by, it may end up stranded in a very dangerous place. To
E. coli
these false signs are noise it must filter out of its circuits.
    To explain how
E. coli
filters out noise, I will draw a wiring diagram. An arrow with a plus sign means that a signal or a gene boosts the activity of another gene. A minus sign means that the supply of protein is reduced. The first link in this circuit is from the outside world to the inner world of
E. coli.
When the microbe senses danger, it sometimes responds by producing a protein called FlhDC.

    FlhDC is one of
E. coli’
s master switches. It can latch on to many spots along
E. coli’
s chromosome, where it can switch on a number of genes. These genes make many of the proteins that combine to make flagella.

    In this simple form,
E. coli’
s flagella-building circuit has a major flaw. It can turn on flagella-building genes in response to stress, but it also has to shut them down as soon as the stress goes away. Once the microbe stops making new FlhDC, the old copies of FlhDC gradually disappear. As they do, the genes FlhDC controls can no longer make their proteins. The complex assembly of flagella comes screeching to a halt in response to the slightest improvement. When conditions turn bad again, this circuit has to fire up its flagella machine from scratch. In a crisis, those delays could be fatal.
    E. coli
does not fall victim to false alarms, however, because it has extra loops in its genetic circuit. In addition to switching on flagella genes, FlhDC switches on a backup gene called FliA.

    FliA can switch on the flagella genes as well.

    But FliA is also controlled by another protein, called FlgM. It grabs new copies of FliA as soon as
E. coli
makes them, preventing them from switching on the flagella genes. Here is the circuit with FlgM added:

    FlgM cannot keep FliA repressed for long, however, because
E. coli
can expel it through the same syringe it uses to build its flagella. As the number of FlgM proteins dwindles, more FliA genes become free to switch on the flagella-building genes.
    Here, at last, is the full noise filter as reconstructed by Alon and his colleagues:

    This elegant network gives
E. coli
the best of all worlds. When it starts building flagella, it remains very sensitive to any sign that stress is going away. That’s because FlhDC alone is keeping the flagella-building genes switched on. But once
E. coli
has built a syringe and begins to pump out FlgM, the noise filters kick in. If the stress drops, so does the level of FlhDC. But
E. coli
has created enough free FliA genes to keep its flagella-building genes switched on for more than an hour. If the respite is temporary,
E. coli
will start making new copies of FlhDC, and its construction of flagella will go on smoothly.
    E. coli
can filter out noise, but it’s not deaf. If conditions get significantly better,
E. coli
can stop making flagella. Its extra supply of FliA cannot last forever. The proteins become damaged and are