Holding back evolution

Gene mutations that are beneficial on their own combine to slow down progress

Evolution may be an exercise in diminishing returns, two new studies of bacteria suggest. When beneficial mutations team up in an organism, they tend to hold one another back.

The results, reported in the June 3 Science, could mean that the more evolutionarily fit an organism gets — reproducing more — the harder it becomes to improve on that success.

Experiments in which bacteria evolve in laboratories commonly show that the microbes initially increase in fitness rapidly, but then slow down over time. Scientists didn’t know whether that was because really good mutations that produce big fitness gains happen early on (and later beneficial changes tend to have smaller effects), or whether mutations interfere with one another.

To find out, an international team of researchers examined five mutations that appeared in a strain of E. coli that had been growing in the lab for thousands of generations (SN: 1/31/09, p. 26). The scientists made 32 new strains of E. coli, each containing one of the possible combinations of the mutations.

Previous experiments combining mutations in a single gene had wildly different effects, with some combinations boosting fitness well beyond the benefit of either mutation alone. Other combinations were disastrous, even though each mutation was individually beneficial. The team didn’t know what to expect from pairing changes in different genes.

“My naïve hope was that we’d see really dramatic, idiosyncratic interactions,” says coauthor Tim Cooper, an evolutionary biologist at the University of Houston. “I really wasn’t expecting to see this gentle but consistent pattern.”

The pattern Cooper’s team saw was that when beneficial mutations were combined, the organism wasn’t as fit as would be expected if each mutation contributed its full measure. Only one of the five mutations consistently made the bacterium reproduce itself faster — indicating greater fitness — regardless of which other mutations it was paired with. The other beneficial mutations seemed to impair one another, an interaction biologists call negative epistasis.

Independently, researchers led by Christopher Marx, a microbiologist and evolutionary biologist at Harvard, conducted a similar experiment with a methanol-eating bacterium called Methylobacterium extorquens. They found similar results: One of several mutations increased the bacteria’s fitness by the same amount regardless of which other mutation it was paired with. The other mutations still allowed the bacteria to perform well, but not as well as expected. And the amount each beneficial mutation could speed up the bacteria’s growth was less in faster-growing bacteria carrying other beneficial mutations.

Both of the experiments grew bacteria under constant conditions and may not reflect what happens in the real world with constantly changing conditions, says Joshua Plotkin, a molecular evolutionary biologist at the University of Pennsylvania in Philadelphia. Still, he says, these experiments provide the most detailed mechanisms and complete data to date about how genes interact with one another in evolution. “It’s the kind of experiment Darwin would have loved to be able to do.”

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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