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Evolving enzymes in the lab

This week's paper is another example of how nonrandom selection from among random variants can solve problems so difficult that we are unable to "design" a solution. As in an earlier post, the selection process was automated, not requiring the human judgement used in breeding crops or dogs.

"Selection and evolution of enzymes from a partially randomized non-catalytic scaffold" was written by Burckhard Seelig and Jack Szostak, both of Boston, and published in Nature (448:828). Their goal was to evolve an enzyme to link two RNA bases together in a particular way, a reaction not found in nature.

Enzymes are biological catalysts, which speed the rates of chemical reactions. Most natural enzymes (that we know of) are made from protein, but a few are made from RNA, possible relics from a hypothesized "RNA world" where RNA acted both as enzymes and as genetic material. Enzymes made of DNA have never been seen in nature, but laboratory conditions have been designed that allow them to evolve from random DNA sequences (Science 286:2441).

Designing an environment where protein-based enzymes could evolve, without using living cells, was actually trickier than earlier evolutionary systems for RNA- and DNA-based enzymes. The authors used a huge library of 1000 billion random DNA variants. All the DNA sequences had two loops, but the contents of the loops varied randomly.

Transcribing all of the DNA variants into messenger RNA and translating the messenger RNAs into proteins is a routine operation; the trick was to leave each protein variant linked to its particular mRNA. Then they stuck one of the substrates of the desired reaction to the RNA-protein combination and turned them loose over a surface with lots of the other substrate bound to it. If the protein could catalyze a reaction to link the two substrates together, the whole complex got tied to the surface and used in the next generation. All the nonfunctional variants got washed away.

The DNA sequences that survived 8 generations of this selective "sieve" were randomly mutated and subject to additional cycles of selection. The whole process took a few days. Evolution can be fast, if the conditions are right. The final product accelerated the reaction over a million times. The authors suggest that this approach could be used to evolve other enzymes that link substrates together. A modified method, saving the enzyme complexes that wash away, could be used to select
enzymes that break chemical bonds rather than make them.

Other recent papers on evolution in major journals:

Genome-wide expression dynamics of a marine virus and host reveal features of co-evolution

Recombination Speeds Adaptation by Reducing Competition between Beneficial Mutations in Populations of Escherichia coli

Cryptic Population Dynamics: Rapid Evolution Masks Trophic Interactions

High-Resolution Genome-Wide Dissection of the Two Rules of Speciation in Drosophila

Heritable Stochastic Switching Revealed by Single-Cell Genealogy

Evolution in the Social Brain

Social Components of Fitness in Primate Groups

A Basal Dromaeosaurid and Size Evolution Preceding Avian Flight

A new theory for the evolution of polyandry as a means of inbreeding avoidance

Adaptive evolution of genes underlying schizophrenia

Reed bunting females increase fitness through extra-pair mating with genetically dissimilar males

Evolution of a single niche specialist in variable environments


I dont see your question about perfusion chambers. Where did you post/send it?

On directed evolution

I am campaigning for recognition of the fact that active goal-directed evolution makes a far better model for evolution of species than the passive neo-Darwinian model.

The requirements for active goal directed evolution are far more easily achieved than is usually credited. There are basically only three conditions to be met:

1) At the time of evolutionary change there must be a direction for favourable evolution perceptible to the evolving organism. For a severely stressed organism this can be as simple as the presence in the same enviroment of a species that is thriving (and may therefore be presumed to have a genetic mechanism of value in that environment).

2) There must be a behaviour that the organism can exhibit that will result in the genome moving in the indicated direction. Since successful species tend to be profligate with genetic material a tendency (as observed) by stressed organisms to indulge in lateral gene transfer is such a behaviour.

3) The situation where an adaptive behaviour moves the genome in a favourable direction must occur sufficiently frequently for organisms exhibiting the behaviour in response to the evolutionary stimulus to be preferentially selected.

Since active evolution of this type has a far better match to both the fossil record and to observed gene distribution I can see no good reason for excluding it from evolutionary models.

Very interesting. I suggest you write up your idea and send it to an appropriate peer-reviewed journal. You will need to thoroughly document two points, either with new data obtained using methods described in detail in your Materials and Methods section, or via detailed discussion of data already published in respected journals. You will need to present data (not unsupported assertions) showing that:
1) stressed microbes become more receptive to horizontal gene transfer when other microbes nearby (potential sources of horizontally-transferred genes) are thriving than when nearby microbes are also stressed, and
2) evolution of a significant number of particular lineages, as shown by detailed discussion of the fossil record, is better explained by horizontal gene transfer than by mutation, selection, and drift.
This is such an important idea -- I'm not suggesting it's likely to be right -- that it would be crazy to forgo the benefits of peer-review, either by failing to submit your work to a peer-reviewed journal or by submitting it in a form that won't be taken seriously (for example, by including unsupported assertions rather than a detailed analysis that shows you have studied the fossil record and the literature on horizontal gene transfer in considerable detail). To encourage you to do so, I have deleted the link to your nonpeer-reviewed PDF.

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