Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [20]
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 destroyed by E. coli’s molecular garbage crews. If the stress does not return in time, the microbe will run out of FliA, and the circuit will shut down. The good times have truly returned.
Scientists are now starting to map the circuitry of genes in other species as carefully as Alon and his colleagues have in E. coli. But it will take time. Scientists don’t yet know enough about how the genes and proteins in those circuits build good models. In many cases, scientists know only that gene A turns on gene B and gene C, without knowing what causes it to flip the switch or what happens when it does.
But Alon has discovered a remarkable lesson even in that tiny scrap of knowledge. He and his colleagues have surveyed the genes in E. coli and a few other well-studied organisms—yeast, vinegar worms, flies, mice, and humans. The arrows that link them tend to form certain patterns far more often than you’d expect if they were the result of chance. E. coli’s noise filter, for example, belongs to a class of circuits that engineers call feed-forward loops. (The loop in the noise filter goes from FlhDC to FliA to the flagella-building genes.) Feed-forward loops are unusually common in nature, Alon and his colleagues have shown. Nature has a preference for a few other patterns as well, which also seem to allow life to take advantage of engineering tricks like the noise filter. E. coli and the elephant, it seems, are built not only with the same genetic code. They’re also wired in much the same way.
LIFE ON AUTOPILOT
An orange winter dusk has settled in. Out my window I can see the webs of bare maple branches. Photons stream through the window and patter on the photoreceptors lining my retina. The photoreceptors produce electric signals, which they trade among themselves and then fire down the fibers of my optic nerves into the back of my brain. Signals move on through my brain, following a network made of billions of neurons linked by trillions of branches. An image emerges. I get up from my desk to turn on the lights. At first I can see nothing outside, but after a moment my eyes adjust. I can still see the trees, down to their twigs.
I must remind myself how remarkable it is that I can still see them. A