A paper appeared recently in Science that reminded me of one of my favorite toys when I was a kid — a rolling-ball maze. Over the years I had a few different varieties, including two- and three-dimensional ones. The basic gist is that a person has to twist and turn the toy to roll a ball through a plastic, transparent maze from the entrance to the exit. Of course there are a lot of dead ends and blind alleys, so it’s pretty tricky, at least at first. Once you learn the path, it becomes trivial.
N�svall et al. (2012) do the same with a protein, manipulating experimental conditions to roll it through dead ends and have it come out in the place they want. Although the printed paper itself and an accompanying commentary by Elizabeth Pennisi paint the results as an advance in understanding evolution, that’s so only if evolution has eyes and a mind like a kid solving a maze. The investigators’ exceptionally intelligent manipulations are relegated to the online supplemental materials.
Reading a brief part of the supplemental Materials and Methods section, entitled “Selection for bifunctional HisA mutants,” is enough to see the absurdity of taking the results as a model for undirected Darwinian evolution. The authors write (lightly edited for easier reading):
We plated several independent cultures of a [bacterial strain missing a protein needed to make the essential amino acid tryptophan] on minimal-media+histidine plates to select any mutant that could produce tryptophan without a TrpF enzyme. We included histidine in the medium because previous studies have demonstrated that mutations that confer TrpF activity to Thermotoga maritima HisA results in loss of HisA activity. The expression of the his operon (including hisA) is regulated by an attenuation mechanism that regulates the amount of read-through of a transcriptional terminator before the first structural gene of the operon according to the availability of charged histidinyl-tRNA. As this results in very low expression of hisA in medium containing histidine, we included a mutation which removes the transcriptional terminator, thereby leading to derepressed transcription of the his operon even in the presence of histidine.
In other words:
- They deleted an enzyme that previous work showed could likely be replaced.
- They added the necessary nutrient histidine because previous work showed that mutations conferring an ability to make tryptophan destroyed the ability to make histidine.
- The added histidine would have shut off production of the protein, so they removed the genetic control element to keep it in production.
- Later, once they found mutations to produce tryptophan, they removed histidine from the medium to encourage the production of mutations restoring histidine synthesis.
Roll the ball to the left to avoid one obstacle, roll it backward to avoid another, turn the maze over to drop the ball into the next corridor. . . . Needless to say, this ain’t how unaided nature works — unless nature is guiding events toward a goal.
1. Nasvall, J., Sun, L., Roth, J. R., and Andersson, D. I. 2012. Real-time evolution of new genes by innovation, amplification, and divergence. Science 338, 384-387.
2. Pennisi, E. 2012. Gene Duplication’s Role in Evolution Gets Richer, More Complex. Science 338, 316-317.
Image: labyrinth of Villa Pisani, Stra (Venice, Italy)/Wikicommons.