August 17, 2007
Scientists Use Accelerated Evolution To Develop New Enzyme

Natural selection can only select between mutations that occur naturally. The number of mutations that might occur naturally in humans is limited by the number of humans and by which mutations occur in each human. In theory if one could search through a much larger set of mutations one should be able to find genes which code for better enzymes and better versions of other components of our body. Some scientists have shown that they can generate and test a large number of potential enzymes to find new designs.

Living cells are not the only place where enzymes can help speed along chemical reactions. Industrial applications also employ enzymes to accelerate reactions of many kinds, from making antibiotics to removing grease from clothing. For the first time, scientists have created a completely new enzyme entirely in vitro, suggesting that industrial applications may one day no longer be limited to enzymes that can be derived from natural biological sources.

HHMI investigator Jack W. Szostak and Burckhard Seelig, a postdoctoral associate in his Massachusetts General Hospital and Harvard Medical School laboratory, show in a paper published in the August 16, 2007, issue of the journal Nature the steps they took to create the artificial enzyme, an RNA ligase that catalyzes a reaction joining two types of RNA chains.

This group at Harvard thinks they can develop better tools to select for enzymes that rise to a higher level of performance.

Szostak's approach relies instead on evolution. The technique enabled the researchers to generate a new RNA ligase without any pre-existing model of how it would work. According to Szostak, “There is no known biological enzyme that carries out this reaction.”

To create one, the researchers assembled a library of 4 trillion small protein molecules - each with slight variations on an initial protein sequence — then subjected those molecules to evolutionary selection in the laboratory. “Here,” Szostak says, “the hard work is in designing a good starting library, and an effective selection process. Since we do not impose a bias on how the enzyme does its job, whatever mechanism is easiest to evolve is what will emerge.”

The enzyme that emerged from the group's experiments is what Szostak characterizes as “small and not very stable, and not very active compared to most biological enzymes.” Nevertheless, Szostak's group is optimistic about their ability to select for versions of the enzyme that are more stable and more active.

Evolution by selection between whole organisms is too slow a way to turn up better designs. Computer simulations and automated lab equipment that generates more real life variations of proteins will some day allow us to search much more deeply through the space of all possible protein shapes to turn up much better genes. In order to give ourselves higher performing bodies we will some day replace some human genes with variants found in labs.

Share |      Randall Parker, 2007 August 17 12:02 AM  Biotech Advance Rates


Comments
Larry said at August 17, 2007 1:02 PM:

I keep wanting to apply the notion of mutation to cancer. If you have a group of cells that undergo an episode of mutation, some of the mutant cells might reproduce at a high and uncontrollable rate, i.e., be cancerous. Most of the mutants would be defective in that either they'd die on their own, or the body's cleanup crews would pop their bubbles. They don't matter, as long as others could survive and reproduce.

Observing the resulting cells might tell you little or nothing about the mutagen, any more than radiation-induced mutants can be traced back to a specific substance. At best, perhaps the mutants in various cases might "discover" the same reproduction techniques. Those techniques could become the vector for therapies.

I'm sure this idea is not original, but I haven't seen it discussed, so I had to get it off my chest.

Kralizec said at August 18, 2007 8:54 AM:
Evolution by selection between whole organisms is too slow a way to turn up better designs. Computer simulations and automated lab equipment that generates more real life variations of proteins will some day allow us to search much more deeply through the space of all possible protein shapes to turn up much better genes. In order to give ourselves higher performing bodies we will some day replace some human genes with variants found in labs.
It does seem likely that technicians in our time or in some future time will use mutation and selection pressure to select for new proteins and new genes. The criterion of selection will be fitness for some purpose, defined by someone directing the work of the technicians. In some cases, men will apply the results to themselves; in other cases, some will apply the results to others, attempting to make them better human beings simply or better tools for some purpose.

It seems the engineered solutions will often be judged successes; some human beings will appear to have been made better in some way and for someone's purposes. But some of us think human beings have been evolving for some 4,000,000,000 years, while we have first-person accounts of our ancestors' circumstances for only the past few centuries, and some precise measurements going back just a few years or decades. The lines alive today and tomorrow are the lines that will have made it through 4,000,000,000 years of we-scarcely-know-what. It does seem likely, as you say, that their living representatives will change themselves and each other; in the lifetimes that follow, some of those lines will be extinguished by mistakes or ill use, while others will live for indefinite times and perhaps live well.

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