Thursday, September 26, 2013

insights from directed evolution

Is their any reason for using the term "directed evolution" instead of the old "artificial selection"?  Well, "natural selection" was an analogy to "artificial selection" -- and the analogies in evolutionary computing continue.  The term "directed evolution" attempts to reverse this and treat "undirected evolution" as the original inspiration and merely be a speeding up of the natural process.

However, "directed evolution" of necessity must, to be effective in a large number of cases, involve a means of skipping between the islands of functionality in protein space:
Though mutation and screening is the essence of directed evolution, there are many factors that combine to turn the process into as much of an art as a science. These considerations include initial protein choice, mutant library construction, and method of screening.(here)
Initial protein choice: starting off the process at a point that is likely to get you what you want, a key location in what you hope is an archipelago of related functionality.  Mutant library construction: this is actually the method for not being bogged down by the typical Darwinian problems with searching nucleotide sequence space -- the sort Michael Behe discusses at length in The Edge of Evolution.  Method of screening:  In natural selection, nature is a terrible screener for the once-in-100-millenia innovation.  Just because an organism has a prize-winning genetic innovation, this doesn't mean that the noise in the innovation-detection system won't overwhelm it.  The survival/reproductive advantage may be washed out in the collective effect on survival, not the least of which is natural danger.  Walk by a tiger, and the innovation may be lost to bad luck, and there is no shortage of this sort of bad luck in the natural world.  So a protein engineer must have a better detection system, in order to ensure that he recognizes what he's looking for once it appears.

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