If you’re unfamiliar with directed evolution, please check out the Wikipedia page. Or find another blog.
Have you read the Wikipedia page? Cool. The power of directed evolution is based on the fact that we can create a huge amount of diversity for a given gene sequence and screen these mutant genes for the activity of their corresponding mutant proteins much more quickly than we can rationally design a better sequence. Rational design involves studying the crystallographic or computational structure of the wild-type protein and guessing how changing the amino acid sequence will affect activity. The two techniques are even more powerful when used together (http://www.sciencemag.org/cgi/content/full/329/5989/285). Crystallographic or computational data can be used to find the residues that are the mostly likely to affect activity. These residues can be mutated while ignoring the rest of the sequence, and these mutants can be screened for activity.
The ability to modify enzymes and other biomacromolecules in order to create useful synthetic biological systems suggests some pretty awesome possibilities. Consider that earlier this year Venter et al. created the first synthetic organism (http://online.wsj.com/article/SB10001424052748703559004575256470152341984.html). The proteins and RNA that we optimize can now be genetically encoded into the genome of synthetic organisms! Now consider the possibilities: organisms that produce fuels and drugs, that rapidly break down garbage or clean up oil spills. Think of an organism that can live off of nothing more than some salts, air, and light. Think of the potential to create synthetic multicellular organisms. Consider the following (http://www.dailygalaxy.com/my_weblog/2009/07/stephen-hawking-the-planet-has-entered-a-new-phase-of-evolution.html): “But we are now entering a new phase, of what Hawking calls "self designed evolution," in which we will be able to change and improve our DNA. "At first," he continues "these changes will be confined to the repair of genetic defects, like cystic fibrosis, and muscular dystrophy. These are controlled by single genes, and so are fairly easy to identify, and correct. Other qualities, such as intelligence, are probably controlled by a large number of genes. It will be much more difficult to find them, and work out the relations between them. Nevertheless, I am sure that during the next century, people will discover how to modify both intelligence, and instincts like aggression." “
So what are the problems currently associated with directed evolution? In the next couple of posts I’ll talk about problems with current screens, specifically covering 2 topics in detail: throughput and versatility.
