Free Microcosm by Carl Zimmer Page A

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, which leads to more permease, which leads to more lactose. The feedback drives
E. coli
into a new state, in which it produces beta-galactosidase and digests lactose as fast as it can.
    Once it becomes eager,
E. coli
will resist changing back. If the concentration of lactose drops, the microbe will still pump in lactose at a high rate, thanks to all the permease channels it has built. It can supply itself with enough lactose to keep the repressors away from the operon so that it can continue making beta-galactosidase and permease. Only if the lactose concentrations drop below a critical level do the repressors suddenly get the upper hand. Then they shut the operon down, and the microbe turns off.
    This sticky switch helps to make sense of Novick and Weiner’s strange experiments. Two genetically identical
E. coli
can respond differently to the same level of lactose because they have different histories. The reluctant one resists being switched on while the eager one resists being switched off. And both kinds can pass on their state to their offspring. They don’t bequeath different genes to their descendants.