Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [60]
In different situations, natural selection may favor some mutation rates over others. Tenaillon and his colleagues have observed the average mutation rate in E. coli as it colonizes a mouse. Early on during the colonization, when the bacteria are experiencing a lot of stress, high-mutation microbes are more common. When the bacteria have established stable colonies in the guts of the mice, low-mutating microbes take over. Antibiotics may also drive the rise of high mutators because they can evolve resistance faster than bacteria that mutate more slowly.
Some critics are skeptical of directed mutation, hypermutation, and their intellectual offspring. John Roth of the University of California, Davis, and Dan Andersson of Uppsala University in Sweden argue that Cairns did not discover anything out of the ordinary in his original experiments. The lac operons in the bacteria he used were not entirely shut down, Roth and Andersson claim. They could still produce a few proteins, allowing the bacteria to avoid starvation. An ordinary, random mutation might have copied the lac operon in a microbe, allowing it to digest more lactose and grow faster. Its descendants might accidentally have made a third copy of the genes, and natural selection might have favored that mutation as well.
Through nothing more than spontaneous mutations and natural selection, Roth and Andersson argue, E. coli can expand its collection of lactose-digestion genes. And as the number of copies grows, it becomes more likely that an ordinary mutation will restore one of the operons to good working order. Any microbes that gain a working operon will suddenly multiply far faster than the other bacteria. Mutations may then remove the defective copies, leaving the microbes with a single good version. This process creates the illusion of directed mutations, Roth and Andersson argue, when nothing of the sort has taken place.
The debate, which continues to rage, matters both to the practice of medicine and to our understanding of how life works. If microbes do depend for their survival on an ability to change their mutation rates, then blocking that change could be a way to kill them. Floyd Romesberg has shown that preventing E. coli from raising their mutation rate prevents them from evolving resistance. He and his colleagues are now trying to turn that discovery into a medical treatment. They hope that someday people who take antibiotics will also be able to take a drug to stop microbes from increasing their mutations.
Some scientists suspect that animals and plants can also manipulate their mutations to cope with stress. Susan Lindquist of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and her colleagues discovered that fruit flies have a buffer to protect themselves from the harmful effects of mutations. A harmful mutation might cause a protein to fold incorrectly. But the fruit fly’s heat-shock proteins can fold it into its proper shape. Over many generations, Lindquist argues, the fruit flies can generate a lot of genetic diversity that could not exist without the help of their heat-shock proteins.
Lindquist discovered that stress unmasks these mutations. Raising the temperature, adding toxic chemicals, or otherwise abusing the flies makes even normal proteins go awry. The heat-shock proteins become so overworked that they abandon many of the mutant proteins to assume their true shapes. These proteins can have drastic effects on the flies, altering their eyes, wings, or other body parts.
Lindquist proposes that heat-shock proteins let the flies build up a supply of mutations that help them survive a crisis without having to suffer their ill effects in less stressful times. An unmasked mutation may prove helpful to the flies, and new mutations can allow it to remain unmasked even after the stress has disappeared. Lindquist and her colleagues have found a similar mutation buffer in plants and fungi,