Dave Micklos (DM): I'm Dave Micklos of Cold Spring Harbor Laboratory. I'm here with Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and we're talking about Neanderthal and genetics.

So who was Neanderthal and why are people so interested in him?

Svante Pääbo (SP): Neanderthals were a group of humans that existed in western Asia and Europe until they became extinct around 30,000 years ago, and they are fascinating I think because they are truly our closest evolutionary relatives; no other organism is as closely related to humans today as they were. So it's very fascinating to compare us to them, because we can then really look at what is it that makes us unique compared to everyone else on this planet.

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DM: And you are now involved in sequencing the entire set of genetic instructions of Neanderthal. And what will those exact instructions, its genome, tell us about us?

SP: So far we have the human genome, our own genome, and we have the genome of the Chimpanzee, our closest living relative. So we could then find all the changes and all the features in our genome that have changed on the evolutionary linear chart since we shared a common ancestor with the chimps. But that was quite a long time ago; say 5 to 7 million years ago, when we will now have the genome of our closest relatives, of the Neanderthal, we will be able to say “what changed in the last little bit of human evolution; the last 300 – 400 thousand years, when fully modern humans appeared for the first time?” So these are then guys with skeletons that are indistinguishable from ours, and among those genetic changes we hope that there will lay hints about what sets us apart, the things that made human technology possible, that made art possible, that made it possible for us to colonize the entire planet.

DM: Now the first human genome took us 15 years to accomplish; how long do you think it will take to accomplish the Neanderthal genome, and where are you in that process?

SP: So at the moment where we are we've worked 2 years seriously on this, and we have a first very rough draft of the genome so we can get the first overview; at the moment we are at the point where we have seen around 65% of the Neanderthal genome at least once, so we can sort of make windows and go over the Neanderthal chromosome and at least see more than half of the genetic information that is there. And we hope that within the next two years we will actually have almost all of the genetic information.

DM: Now you mentioned that you would like to see how we are similar or different to Neanderthal and similar or different to chimps. Could you give us an example of a gene that we share with Neanderthal but that we do not share the same variation with chimps?

SP: So one gene that we have been particularly interested since a long time [ago] actually is a gene called FOXP2, and that's the only individual gene that we know of today that has to do with language and speech ability in humans. And we know that because if we have a mutation in a human that knocks out one copy of this gene that we got from our mom or our dad, then we have a severe language problem or a speech problem, primarily about articulation, actually muscle control in the mouth and in the throat when we speak. And this gene is interesting because it has two changes in the protein it encodes that is specifically humans that you see in no other apes or monkeys. So we were very interested in looking at Neanderthals and seeing if this is something unique to modern humans or not and somewhat to our surprise actually, it turned out that we share this with Neanderthals; Neanderthals look just like us with respect to this genetic change.

So that then suggests that at least from the very little that we know about speech, there is no reason to assume that they could articulate in speech as we do; that said of course, there are lots of genes there to test to do with speech that we don't know yet where they could have differences, but from the very tiny little thing we know today there is no reason to assume they weren't like us.

DM: Now your first experiment, which you did more than 10 years ago with Neanderthal DNA, worked with the mitochondrial chromosome (a very small chromosome). Why did you choose that to work with initially?

SP: So the mitochondrial DNA is particularly useful because it exists in many, many copies per cell, and in every cell we have for a typical nuclear gene just two copies; one from our mom and one from our dad. [With] the mitochondrial DNA we have sever hundred or even thousands of copies per cell, and they all come from our mother, but it's easier to retrieve in an ancient specimen just because there are more copies there. It also gives a picture that's easier to interpret of our genetic history, since as it's inherited only though the maternal side; my mother, my grandmother, my great grandmother; it can trace female history back in a very easy way. But it's of course just a tiny part of our entire genetic makeup, so now it's fascinating to be looking all over the genome.

DM: Now that initial experiment was important, and what did that experiment tell us that was really pretty critical?

SP: So what it showed was that for this part of our genome, for the mitochondrial genome, the Neanderthals fall outside our variation. So where as all humans on the planet, in their mitochondrial DNA, trace their ancestry back to a common ancestor between a hundred and two hundred thousand years ago, the Neanderthal lineage goes back something like half a million years or a bit more, so this also showed that the Neanderthals then did not contribute any mitochondrial DNA to us today. So there was no indication that we mixed when we met from the mitochondrial DNA; now of course we are in the process of analyzing the entire nuclear genome and we might be able to pick up even a small contribution that may have happened, so in just a month or two I think we will be able to say much more about this.

DM: Now of course what you're touching on is sex; people are always interested in sex, and the question is during the time we spent together in Europe about 30,000 years ago, our ancestors and Neanderthals, did we ever mix it up, and it's an open question but do you think we'll be able to answer that question with certainty once we have the whole sequence?

SP: As a geneticist what I am really interested in [is] did one have children back then and did those children contribute to our variation today; I'm sure in a way that they had sex, but what I am interested in was it productive in the sense, giving offspring that contributed to us. And that I think we will be able to answer quite rigorously with the genome sequence we will have.

DM: Now you followed up on your earlier work with the mitochondrial chromosome by sequencing the entire mitochondrial chromosome from 5 or 6 individuals; that was just within the last year. What did that experiment tell you?

SP: So what we can then do is start studying how much variation there is among Neanderthals genetically in the mitochondrial genome, and compare that to what we find in people living today to get a perspective; was it a lot of variation or was it little variation. And one fascinating thing in human variation is that when we compare ourselves to our closest living relatives, the great apes, we have quite little genetic variation which reflects if we go back to the rather small population in Africa that expanded around 100 thousand years ago.

Now a big question was “Are the Neanderthals like the apes in having a lot of variation or like us in having little variation?” And the answer is very clear; they were like us in having little variations, and in fact the variations seem to be more on the scale of Europeans or Asians today rather than humans worldwide. So it suggests that they, also just like us, probably have a history where they went through bottlenecks where there were few individuals around that then expanded again and had more offspring; perhaps as a result of glaciations, they survived through at least three ice-ages.

DM: Well one final question; once you have the whole Neanderthal sequence, would it be technically feasible to recreate a Neanderthal in the flesh? Of course this is Jurassic Park, but maybe a little easier.

SP: I mean, you can of course speculate about technology that we don't even have today, where one would say in theory now, hypothetically, you would take a human embryo and replace thousands and thousands of genetic variants and create a Neanderthal. Perhaps in a science fiction novel you could imagine that; it's also quite clear that it would be ethically, totally indefensible to do something like that. You would create a human being simply to satisfy your scientific curiosity which is not something any responsible person would contemplate I think.