Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [59]
Over the course of six days, a hundred colonies emerged. Cairns examined their lac operon and found that a mutation had struck the microbes, allowing them to switch on the operon again. Cairns calculated that if the bacteria had been mutating spontaneously at their normal rate, only a single colony would have formed in that time. Instead, Cairns concluded, these microbes had acquired working genes a hundred times faster than they should have.
“Cells may have mechanisms for choosing which mutations will occur,” Cairns and his co-authors wrote.
These “directed mutations,” as they came to be known, caused an uproar. The idea that E. coli could respond to a crisis by mutating a specific piece of DNA smacked of Lamarck. Critics claimed that Cairns’s hypothesis was practically mystical, requiring E. coli to know that mutating a particular part of its DNA would help it in a particular crisis. A wave of other studies followed as scientists tried to figure out just what was happening.
A consensus emerged that these mysterious mutations were not precisely directed toward any particular goal. Many of the bacteria that regained the ability to feed on lactose also carried new mutations on genes that had nothing to do with lactose. Instead of directed mutations, scientists began to speak of “hypermutation.” And by hyper, they meant that during a crisis E. coli’s mutation rates could soar a hundred-or even a thousandfold. Several studies identified E. coli’s lo-fi polymerases as the enzymes that created these extra mutations.
Some scientists argue that hypermutation is an elegant strategy to ward off extinction. Normally, natural selection favors low mutation rates, since most mutations are harmful. But in times of stress, extra mutations may raise the odds that organisms will hit on a way out of their crisis. To avoid starving, E. coli does not need to know that a small mutation to the switch controlling its lactose-digestion genes will hit the jackpot. It just has to change enough DNA until it changes the right one.
Hypermutation has an obvious risk: along with a beneficial mutation, it can also cause many harmful ones. Susan Rosenberg of Baylor College of Medicine and her colleagues argue that E. coli minimizes this risk by spreading it across an entire colony. When E. coli produces extra mutations under stress, an individual microbe experiences them only in one narrow region of its DNA. From one microbe to the next, that window of mutation is in a different spot. As a result, the bacteria are not crippled by mutations all across their genome. At the same time, though, new versions of almost every gene in the E. coli genome can emerge in a colony. When a few microbes hit on the winning solution, they can start growing quickly.
Hypermutations may be a useful way for E. coli to cope with stress, but they may have evolved for very different reasons. Olivier Tenaillon of France’s National Institute of Health and Medical Research points out that it takes a lot of energy and material to build hi-fi polymerases. In times of stress, E. coli may not be able to afford the luxury of accurate DNA repair. Instead, it turns to the cheaper lo-fi polymerases. While they may do a sloppier job, E. coli comes out ahead on balance. Natural selection, Tenaillon proposes, didn’t favor higher mutation rates—just cheaper repairs.
Even if the changing mutation rate in bacteria arose as a side effect, it may still be useful. Tenaillon and his colleagues have demonstrated that E. coli varies enormously in its mutation rate. Under stress, one microbe may mutate a thousand times faster