"By taking the text from one organism and another organism and aligning them up, you can see what evolution thought was important enough to hang on to"

AA: If you've got the human genome sequenced, why do you need to sequence the mouse genome, unless there's some really bad mouse diseases you want to work on?

LANDER: I mean, the truth is, we don't know how to read the real content of the human genome. We can get the 3 billion letters laid out, but we don't know which ones matter a lot, which ones really control the proteins that make up your body, control the regulation of the genes during the development of an embryo. There are two ways we're going to learn how to read DNA. We could do an experiment. We could try changing every letter of the DNA in a cell or in a human being or something and seeing if it has an effect.

AA: Yeah, but you can't do that with a human.

LANDER: No, it would be unethical, it would be utterly impractical. You couldn't even do that with an animal model, because it would take way too long. But happily, there is one process that's been around for quite some time that does just that. It's evolution. We have a common ancestor with the mouse 100 million years ago. And evolution started tinkering with that common ancestor, making a random change here, seeing if it was a good idea or not. Probably not a good idea, throws it out. Makes another random change, another random change... 100 million years later, you've got mouse, you've got human, and when you line up the two DNA sequences, you see that some bits of the text have been very carefully preserved. Those are the bits that really matter.

	"Jurassic Park notwithstanding, we really can't get DNA from all the different fossils."

AA: What do those bits that are just the same in the mouse and in the human tell us about humans?

LANDER: Well, the bits, for example, might be a gene that codes for some skin protein and if there was a mutation in those letters, the organism would die. Evolution would select against it. Those letters have been preserved because they mattered to both organisms. So, by just taking the text from one organism and another organism and aligning them up, you can see what evolution thought was important enough to hang onto, to keep preserved in roughly the same form over 100 million years. And since evolution is this great experimentalist, this wonderful tinkerer who's been keeping notes on all its experiments, we can learn so much more by peeking into essentially evolution's lab notebook.

AA: Is there any fossil DNA? Could you look at some failures and see how they match up?

	"We now have the parts list of the Boeing 777. It doesn't mean we know how the airplane flies."

LANDER: Right. Of course the thing about evolution, it doesn't quite keep its lab notebook the way a scientist would. A scientist is supposed to write down the failures and the successes. Evolution just keeps the successes. It throws out all the failures, and that's kind of cheating. It would be nice if we could get DNA out of the failures, out of the evolutionary dead ends that didn't work out, and you can do that occasionally. It turns out you can get DNA out of Neanderthal fossils, and sequence that DNA. We know now that Neanderthal wasn't an ancestor of modern man, but it was a cousin. We can do that with a few other extinct animals, but for the most part, Jurassic Park notwithstanding, we really can't get DNA from all the different fossils.

AA: Why do you want to go to the mouse next? Why don't you want to go to the chimps?

LANDER: Too close! The chimps were interesting, but the chimp is 99% the same as you and me. Only 1 letter in a hundred has changed, so we don't get to see what's preserved and what's not preserved, because almost everything's preserved. The tough thing with the chimp is figuring out which of the changes made the difference between us and the chimp. You really can't learn anything. You've got to go some distance where evolution has had a chance to throw out the chaff and keep the wheat.
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