BEACON Researchers at Work: Directed and Real Evolution

This week’s BEACON Researchers at Work blog post is by University of Texas at Austin faculty Andy Ellington.

Ellington PortraitEvolution in Action. That’s the BEACON motto. It always struck me as a bit wishful. Because evolution is mostly glacial. Sure, it can bury you over time. But it’s like that scene in “A Fish Called Wanda” where Ken is running over Otto with a steamroller. You really have to be stuck to see it.

Anyway, my lab works on directed evolution. Which is the much faster, more engineered younger brother of natural selection. We can make molecules and pathways and organisms jump on our own timescale, which is typically shorter than the timescale of the typical graduate student thesis, although some of those can be glacial, too. We introduce many mutations at the outset or else carry out procedures that are inherently hypermutagenic, direct populations through bottlenecks with great speed, and amplify the survivors with efficiency. This works whether we’re talking about molecules in vitro or viruses or microbes that have decent replication cycles. It does not work if we’re talking about rabbits. We’ll have to work on that.

But this brings up the interesting and useful point I was not making. BEACON is as much about education as it is about science. And the general populace can think about something like a rabbit evolving much more easily than they can something like beta-lactamase (although the evolution of drug resistance is one of those canards that the Creationists generally steer clear of, for good reason). And since we can’t run fast cycles of rabbit evolution, turning fluffy bunnies into the sort of killer rabbits that stymied John Cleese in a different Python movie (Holy Grail with its Holy Hand Grenade of Antioch), it is not as easy to viscerally demonstrate evolution that resonates.

But of course we would all argue that it’s the same thing: generating and culling alleles is evolution. This is the fundamental definition. Diversity. Selection. Replication. At any timescale, in any system. I sometimes have trouble making this point when talking with colleagues about origins, because many biologists are closet Vitalists who sadly want to separate discussions of origins from discussions of evolution. Nonetheless, the fundamentals are sound, just like with the economy.

Now, how do we better represent these fundamentals to the public? My goal in BEACON has in part been to show Evolution in Action by developing kits that show ribozyme evoluton in real-time. Ribozyme populations placed into a very good environment of enzymes and substrates can lead to their own reproduction and winnow to those variants that are the most active, with a parallel fluorescence readout.

I’d now like to better encourage the spread of directed evolution throughout the BEACON community. I think we can begin to discuss how to encourage experiments that demonstrate evolution and that lead to products that are of commercial interest and value. And that these will feedback and reinforce our mission statement.

Since many BEACON-ites are interested in computer evolution, this will require a fundamental restructuring of how we meld computer and biological processes. We could have a wonderfully fun discussion of whether electrons replicate or not, and if they don’t whether or not computer algorithms are in fact evolving. But it would be a somewhat fruitless discussion, because in reality all we’re doing is moving the goalposts: just as I claim my enzyme bath allows ribozymes to replicate, computer scientists can claim that their cozy electronic interiors allow programs to replicate. Of course, there’s also the modeling of evolution that is not evolution itself.

Both types of research may find their way into biology. Have we ever really thought about how to make automatons and viruses more alike? If I wanted to make a virus that had at its core rule sets that were not unlike the rule sets in an algorithm, could I do that? That would be super hard and interesting. In contrast, can computer scientists make automatons that have at their core rule sets that resemble those of viruses. This, this is a much more worthy goal.

Modeling is a more obvious crossover, especially with Avida and all. Still, the use of Avida to retrodict and the use of Avida to predict could be refined. In particular, can viruses or other synthetic systems be set up to run down the same pathways that Avida has already plumbed, and will they get th same answers? This is particularly important because the time is coming, and coming quickly, when we will use computation to plumb fitness landscapes in advance of evolution. Tools already exist to begin to predict host:pathogen interactions, and the further ability to predict evolutionary dynamics of the random “viral chatter” that goes on between human populations and the many things assaulting human populations is of particularly import, given the recent news of how Koyaanisqatsi seems to be at our doorstep, at least for viruses.

I am reminded by a venerable senior colleague that the last reference is only for the olds, like me. For those of you of a certain age, you may remember the iconic crying Indian, saddened over the destruction of our environment, that would show up on public service announcements. Around that time, there was also a movie, Koyaanisqatsi, nominally translated from Hopi as “World Out of Balance,” that was anextended word picture that showed how we were moving away from nature. Yeah, we were all hippies back then. Anyway, when Ebola shows up on your doorstep and says ‘hi,’ it seems to me that the world is out of balance, and that it’s time to do something more than cry about it.

For more information about Andy’s work, you can contact him at ellingtonlab at gmail dot com.

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