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Tuesday, August 14, 2007

The best is the enemy of the good

Slightly helpful mutations in E. coli much more plentiful than thought.

Beneficial mutations in the bacterium Escherichia coli occur 1,000 times more frequently than previously predicted, according to research from a group in Portugal.

In a study of E. coli populations of various different sizes, Isabel Gordo and her collaborators at the Gulbenkian Science Institute in Oeiras, Portugal, found that thousands of mutations that could lead to modest increases in fitness were going unseen because good mutations were outperformed by better ones1. The authors say that the work could explain why bacteria are so quick to develop resistance to antibiotics.

"It's changed the way I think about things," says Frederick Cohan, a biology professor at Wesleyan University in Middletown, Connecticut. He adds that although the principles involved were understood, no one expected to find such a high rate of adaptive mutation.

In very large populations of an asexual organism like E. coli, adaptive evolution is a game of winner takes all. When one organism develops a mutation that gives it an advantage over its brethren, its genome quickly becomes dominant in the population, taking control in what's known as a selective sweep. When this happens, other mutations that might offer a slightly less adaptive response are generally lost.

It's changed the way I think about things.

Frederick Cohan

Evolutionary biologists know this masking of weakly adaptive mutations as clonal interference, and some suspected that a slice of beneficial mutations were being missed because of it. The work by Gordo and her colleagues differs from that in previous studies in the size-range of the populations looked at. The larger populations contained 10 million cells; the smaller had 20,000. The number of mutations was 1,000 times higher in the smaller populations than in the larger populations.

Success in numbers

Cohan says that he's amazed at the idea, implicit in the paper, that a mutation has many more ways to confer fitness than are normally seen. "That there are so many possible mutations is telling us [that] many different genes can be involved in an adaptive response. I think this is saying that hundreds to thousands of genes are probably involved."

What is less clear is how the minimally beneficial mutations normally masked by interference might contribute to the speed with which bacteria develop antibiotic resistance, says Carl Bergstrom, an evolutionary theorist at the University of Washington in Seattle. "I don't see that that's been tested directly," he says. More often than not, antibiotic resistance is acquired not through mutation but through transfer of a small genetic element outside of the genome, called a plasmid.


But transcribing the genes that confer resistance is costly for bacteria, Gordo says, and beneficial mutations might help with that. "Because the bacteria adapt really quickly, resistant bacteria might be able to compensate for the cost of antibiotic resistance." Future studies, she says, could look at responses to antibiotics and other environmental stresses. "A possible next step is to try to understand whether the distribution of effects will be changed much in a different environment, and to try to investigate which types of mutations in which genes are adaptive."

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About The good is the enemy of the best

The good is the enemy of the best." - anonymous quote I ran across this morning.
"The best is the enemy of the good." - Voltaire.

So which is it? It's probably both. In light of the first quote, we can never become so complacent that our way is "good enough." People and organizations must always strive to become better at whom they are and what they do. This is the center of continuous improvement and other process-centric improvement efforts. This idea is also the center of 3M and Google's efforts to set aside time for their employees to work on new (and different) ideas for products to help those organizations jump the boundaries of "we've always done it this way."

On the other hand, we don't want to spend so much time looking for the best that nothing happens. This is where I've heard the Voltaire quote used, particularly when railing against the idea of "best practices." The concern is that people and organizations spend so much time either trying to become the best or trying to find the best way to do something that they never actually get it done. As Hiebeler discussed at KMPro, there really are no true best practices, simply examples of best practices.

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