Dr. Nicole King and Dr. Seth Grant join Cold Spring Harbor Laboratory's David Micklos to discuss how synapses in the brain could have evolved.

Dave Micklos: One final question. You were both discussing earlier the fact that these proteins exist in simple organisms and they are carried forward in complicated ones; you were discussing whether or not these molecules were anticipating something greater or not. So that's an interesting thing to discuss if you could react to that. Nicole King: Well, what we were discussing was essentially what is the derivation of these molecules that, in the case of single-celled organisms, are responding to environmental cues, and then in the brain are responding to each other really. And the idea is that, just like organisms, we can trace the history of genes throughout the tree of life. So genes don't arrive 'de novo'; they have ancestry, and so they evolve within organisms in response to selective pressures from their environments. And what we're beginning to see is that genes that evolved in single-celled organisms to do things like capture bacterial prey or allow cells to divide rapidly when there are nutrients and remain static when there are not, these genes were in place before the origin of animals and then were co-opted to new functions. So going from the transition from single-cells to multi-cellularity, some of these genes started to make proteins that allowed cells to stick together. So they evolved first to do things like capture bacteria or interact with the physical environment, and now they are being moved to an analogous function which is to interact with neighboring cells, and so they have one function that allows them to very readily be evolved to a new function. Seth Grant: I think one of the curious paradoxes must be this: if you have, in a very simple animal, all of the building blocks to build a complex brain, then why doesn't it have a complex brain? And it's because what has happened between the time of the origin of this simple animal and the complex brain, is many, many steps that have been achieved in the construction of that brain. And let me give you a simple idea, going back to the LEGO set: most children with a LEGO set will build little houses or little cars and things like this, but if you go to LEGOLand, you will discover that somebody has constructed a full sized Lego version of the Empire State Building or some extraordinary thing, and you think, "Well, why couldn't I have done that?" And the answer is you could have done that with those building blocks, but you didn't; it took a lot of little steps to get there, and you would have had to make all of those different parts, and gradually work toward that. And that's the notion of evolution; built upon these building blocks, which ultimately can build something rather wonderful and complex. Another simple analogy would be one which we've all heard, which is that the ability to type doesn't mean that you're going to write the works of Shakespeare; it takes a lot of steps in between. The building blocks in and of themselves are not sufficient, there's other aspects to the organization. Nicole King: And it should be said that many mistakes are made along the way also. So of the one example in which a monkey does type Shakespeare, there are millions and millions of examples in which it doesn't happen. So for this toolkit, there are certainly many times in which mutations might have arisen that lead to extinction, and it's the rare example that leads to something like a human brain. Seth Grant: Well if I'm not mistaken I think the number of monkeys that have existed is somewhere in the order of probably about 8 to 10 billion, and only one of them has been Shakespeare. Nicole King: That's right. Dave Micklos: Well thank you both for being here today.

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