Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [83]
The map Babu’s team drew looks a lot like the hierarchy of a government or a corporation. A few powerful genes sit at the top, each directly controlling several other genes. Those middle-manager genes control many other genes in turn, which may control still others. This organization allows E. coli to cope with changes in its environment with swift, massive changes to its biology. Babu’s map also let him survey E. coli’s network down to its smallest circuits.
Once Babu had finished his map of E. coli’s network, he could reconstruct its history. He compared it with the networks in 175 other species of microbes. Babu discovered a network core shared by all of them, made up of 62 genetic switches controlling 376 genes, for a total of 492 links. This core, Babu concluded, existed in the common ancestor of all living things.
This core network offers some hints of what that common ancestor was like. It already had sensors, which allowed it to detect different kinds of sugar and monitor its own energy levels. It could detect oxygen, not to breathe it—since the atmosphere was nearly oxygen free—but probably to protect itself from its own toxic oxygen-bearing waste. This ancestral microbe was already using genetic switches to control iron-scavenging genes, to create the building blocks for proteins and DNA. It was, in other words, a fairly supple little bug.
From that common ancestor every living thing today evolved. Along the way its network evolved as well. The lineage that led to E. coli gained new circuits to sense and feed on new sugars, for example. Experiments on living E. coli have helped shed light on how mutations and natural selection rewired its network. One of the simplest means by which E. coli’s network can be rewired is the accidental duplication of a chunk of DNA. In some cases, the duplication may create two copies of the same switch. If the gene for one of those switches mutates, it may begin to control a different gene. In other cases, extra copies of genes created by duplications are controlled by the switch that turned on the original gene.
The ancestors of E. coli rewired their networks as they adapted to new ways of life. Sometimes only minor tinkering with a circuit would produce an important adaptation—adding an extra switch to a gene, for example, or taking one away. One of these tinkered circuits allows E. coli to sense a drop in oxygen and switch its metabolism over to oxygen-free pathways. It is almost identical, gene for gene, to an oxygen-sensing circuit in Haemophilus influenzae, a species of bacterium that infects the bloodstream. In H. influenzae one switch turns on two genes, which then activate all the other genes required to shift the microbe to an oxygen-free metabolism. It’s a fast circuit, which suits H. influenzae well since it lives in the blood and experiences rapid drops in oxygen as it moves from arteries to veins.
E. coli, on the other hand, does not make snap decisions about oxygen. Living in the relatively stable environment of the gut, it does not experience the sudden, long-term drops in oxygen that H. influenzae does. A slight fluctuation might be a false alarm, which would cause E. coli to invest a lot of energy making new enzymes that would be of no use. And that fact of life is reflected in E. coli’s oxygen circuit. It is identical with H. influenzae’s circuit but for one extra gene, called NarL:
In H. influenzae, Fnr immediately switches on FrdB and FrdC. But in E. coli those genes also need a signal from NarL. It takes time for Fnr to drive the level of NarL high enough to give the two genes both the signals they need. A minor dip in oxygen won’t provide them with enough time to prime the pump.
As E. coli’s network evolved, it became impressively robust. The growth of man-made networks offers some