Exploring the Genetic Code of the Neanderthal Scientists have sequenced DNA from one of humans' closest relatives, the Neanderthal. Guests examine what that prehistoric genetic code might tell us about how these early hominids lived, and why they became extinct. Can the genetic code also answer the question of whether Neanderthals and modern humans interbred?
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Exploring the Genetic Code of the Neanderthal

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Exploring the Genetic Code of the Neanderthal

Exploring the Genetic Code of the Neanderthal

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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow. News about Neanderthals. Two major journals this week - Science and Nature - carry research papers announcing the mapping of parts of the genetic code of one of our closest relatives - the Neanderthals. The DNA the biologists used was taken from a male Neanderthal who lived about 38,000 years ago in present-day Croatia. Scientists say the genetic information they are mining might answer some longstanding questions about how the Neanderthals lived, about their life and actually, why they died out? No one really knows what happened to them. Maybe we'll be able to figure that out.

Joining me now to talk about that and to learn more about this prehistoric DNA are my guests Richard Klein, a paleoanthropologist at Stanford University. He joins us from the campus there. Welcome back to SCIENCE FRIDAY, Dr. Klein.

Dr. RICHARD KLEIN (Paleoanthropologist, Stanford University): Thank you very much.

FLATOW: You're welcome. Edward Rubin is director of genomics division at Lawrence Berkley National Laboratory. He's also director of the Department of Energy's Joint Genome Institute in Walnut Creek, California. Welcome back to SCIENCE FRIDAY, Dr. Rubin.

Dr. EDWARD RUBIN (Director of Genomics Division at Lawrence Berkley National Laboratory): Hello, Ira. Pleasure to be on the program.

FLATOW: Dr. Rubin, tell us about this DNA you sequenced. How much of the genome does it actually represent?

Dr. RUBIN: Right. So, it's just a drop in the bucket. And so, our study that generated about 65,000 bits of genetic information and that's in the context of genome - that's three billion bits of genetic information. So we just barely dipped in.

FLATOW: And what's interesting about this is it's being hailed. In fact, in a paper in Science, Richard Klein, you say that the (unintelligible) were the immediate predecessors of modern humans, and how close were they? Give us a little but of a thumbnail sketch of where they were in relationship to when people were living - or modern-day Homo sapiens.

Dr. KLEIN: Well, modern-day Homo sapiens originated in Africa sometime within the last 200,000 years and spread from Africa to Eurasia about 50,000 years ago. The Neanderthals were already living in Europe at that point. They had begun to evolve there. We can see traces of their features in people as much as five or 600,000 years ago, and they appeared in Europe evolved full blown in Europe by perhaps 150 to 200,000 years ago and then disappeared after modern humans arrived from Africa some time around 35 or 40,000 years ago.

FLATOW: And do we know why they disappeared?

Dr. KLEIN: Well, that's a controversial issue. I think I know why, but not all my colleagues agree.

FLATOW: Well give us your take on it.

Dr. KLEIN: Well, I think basically they were out competed for the same resources that modern human and Neanderthals required. Both groups were hunter gatherers but the modern humans - if we want we can call them Cro-Magnons - having arrived from Africa with very much more advanced technology, probably a different kind of social organization - all sorts of behavioral traits which allowed them to exploit the environment much more effectively than Neanderthals could. And I think that the Neanderthals just suffered from the loss of the food items that they now had to compete for and they became extinct.

Probably, very quickly, in any given local - probably within a few hundred years. Although, it might have taken as much as six or 7,000 years for them to disappear all across Europe starting on the east and moving to the west.

FLATOW: Uh, Rubin can you tell from the DNA more about this story? About the interbreeding and when he disappeared? Add clues to this puzzle?

Dr. RUBIN: Right and so what's important about this study I think is that there has been a hurdle to getting their nuclear DNA from these ancient creatures. The studies show that this is no longer a hurdle so we're going to get a lot more sequence in the very near future. But what we can learn from what we got does begin to give us some numbers about - first of all - you said it was a male and we couldn't tell that from looking at the bone, but if we get the DNA we could tell it was a male if it had the Y chromosome. And as far as what we've learned - we've learned that it appears that the numbers suggest that about 700,000 years ago, Neanderthals or the precursors to Neanderthals - the precursors to Homo sapiens came off a common ancestral population that was a precursor of the common ancestor.

And then the data suggests that around 400,000 years ago the populations went there separate ways with minimal admixture after that point. And that was before we see anatomic - we see in the fossil records representations of Neanderthals and Homo sapiens. So, it suggests that they went there separate ways earlier on and had minimal mixing. Then there's the question that the public is enormously interested in that and that is recent mixing. And our data doesn't support that but it's only a small amount of data. And so I think that with time maybe it'll change. Maybe we'll see hints of that but we don't see any hints with what we have now.

I think as far as the dates of when we come from a common ancestor when the population split - I think those dates will probably hold as we get more data. I think the issue of mixture mixing - I think that will, you know, we'll probably need a whole genome before we're able to nail that one.

FLATOW: We're talking about a specimen that's tens of thousands of years old. How do you find viable DNA in something like that?

Dr. RUBIN: Yeah, so that's a - you know that's an exciting aspect of the work, in that, you wouldn't of thought we could, but what it is, is really - it comes from the fact that most - when you have this carcass in the edge of a cave, it's mostly becomes a nutrient rich resource for bugs and plants to live off of it. You give it 40,000 years and it's mostly what you have in there are the organisms that have been - or the DNA in the organisms that have been living off those nutrients.

But with the increasing through put of sequencing and decreasing costs suddenly we could think we'll maybe if we just sequence and sequence amongst all the microbial contaminants - and using computational tools to sift through it - we would see some - some of the original hosts that Neanderthal and that's in fact what we - what happened now - we were able to use high through put sequencing and see amongst the mixture of DNAs - there was some of that ancient creature that we're interested in and that's why - that's what's - you know science-fictiony about it. A few years ago, we wouldn't of thought that that was feasible and it's only with the increasing through puts of sequencing that now makes it feasible.

FALLOW: Richard Klein, does that mean now we've entered a paradigm shift in anthropology and anthropologists work then instead of looking at the fossils and bones - anthropologists will learn a lot more from looking at the DNA and searching for it?

Dr. KLEIN: Well the DNA has made an enormous difference and it's not just the DNA that has been extracted from ancient Neanderthal bones, but DNA of living humans. And if you go back 20 years there was a popular view in paleoanthropology and human evolutionary studies that the Neanderthals might actually be the ancestors of living humans or at least of living Europeans. And we seem to be in a situation where we're going to argue about that endlessly.

And then in 1987, the Landmark paper was published by Owen Wilson and some of his students at the University of California Berkeley where they showed that if you looked at one kind of DNA in living humans it was clear that all living humans shared a recent common ancestor within the last 200,000 years and that common ancestor lived in Africa. The work was a little controversial to begin with but it was ultimately well substantiated.

Then in 1997, the (unintelligible) group, which has been working with Dr. Rubin, got the first of what we now consider to be ancient Neanderthal DNA - a different kind of DNA than Dr. Rubin has just been talking about. But it was the first chit that the Neanderthals, in terms of their genes, were in fact quite different from us and now the issue as far as paleoanthropologists is concerned is not whether the Neanderthals are our ancestors but the issue that Dr. Rubin referred to a moment ago about whether in fact when modern humans appeared in Europe they might have interbred a little bit with the Neanderthals.

No one, I think, believes today that the Neanderthals are directly ancestral to living humans. But it's all because of genetics that this has changed and what Dr. Rubin's work is going to tell us, ultimately, is whether in fact there was interbreeding and more importantly it'll get at the behavioral differences, I think, between Neanderthals and their selves and then help us to explain who we are and why the Neanderthals aren't here anymore. Why we replaced them?

FLATOW: Dr. Rubin what kind of behavioral differences can you tell by looking at the genes?

Dr. RUBIN: Right. And so, that - those kind of questions are the exciting horizons. And it's a bit like, you know, I like thinking about how the sequence data will change to seal the bid - in that it's a little bit like Egyptianology, when in the past we just had the pyramids. Then eventually, we cracked hieroglyphics and we began to learn things about every day life of Egyptians that we wouldn't of learned from their structures. But before we cracked it - we didn't know what it was going to tell us and I think the same thing with regard to sequence data - genome sequence data - what's going to tell us about the biology in that - that we have bones and we have associate artifacts and that's told us a lot.

And the sequence data is really going to tell us - open this whole new window - it's hard to speculate exactly on what we're going to be able to see through that window and what we're going to learn about Neanderthals really is all based on what we're going to learn about the human genome. Because the human genome, eventually as we sequence thousands of humans, which will be occurring in the next 10 or 20 years, and we're able to associate particular sequence changes with particular biological features. And we're not sure what kind of biology we're going to be able to associate with sequence change.

But when we see that in humans, we'll be able to go back into the Neanderthal genome and say, do they have those sequences changes? And if they do then we'll associate with specific biology.

And so as far as speculating that about what are we going to learn, I can say that we're going to learn, you know, possibilities or things like, you know, people have speculated that there are genes and sequences involved in language.

But I think there's a whole gamut of things that we're probably going to learn. It's just hard to tell at this point.

FLATOW: And questions of intelligence also, perhaps?

Dr. RUBIN: You know, what are we going to learn from the human genome? Are we going to learn about, you know, predilections for violence of all kinds of - or interest in language or interest in music. You know, those are the kind of things that we may learn from the human genome. And if we do then we'll be able to lay it back upon the Neanderthal genome and speculate that they potentially possessed those characteristics.

FLATOW: Richard Klein, are there disagreements among anthropologists that this DNA might settle now?

Mr. KLEIN: Oh yes. I think that a major issue, which may not be all that important but at least to paleoanthropologists is one we argue about, is this question of whether there is a Neanderthal contribution or a Neanderthal contribution to the modern human gene pool.

My own view - and I think this is basically Dr. Rubin's at this point, he can speak for himself, of course - is that if there was one it was probably very small. But we'll be able to say much more about that when we have the complete Neanderthal genome or something like the complete Neanderthal genome and hopefully more than one for more than one individual.

FLATOW: How is…

Mr. KLEIN: And there is this…

FLATOW: I'm sorry. Go ahead.

Mr. KLEIN: And then there is this issue of why the Neanderthals are extinct. Dr. Rubin referred to the possibility that they might or might have had language in the way that we do. We know of a gene in living humans that is involved in speech and language. It's called Fox P2. And it seems to have been fixed by natural selection very, very suddenly, sometime within the last 200,000 years. Can't be much more precise than that.

But it would be very interesting to know what that gene looked like in Neanderthals. Was it like us or was it maybe a little bit more like what would be in chimpanzees?

And with that kind of question in mind we can begin to the get at the issue of whether Neanderthals were enough like us so that we might have expected to survive? They didn't. My guess is that it's going to turn out that they were biologically different from us for genetic reasons - behaviorally different from us for genetic reasons. And that's much of the reason why they disappeared.

FLATOW: We're talking about Neanderthal this hour on TALK OF THE NATION: SCIENCE FRIDAY from NPR News with Richard Klein and Edward Rubin. 1-800-989-8255.

Do you have enough DNA to sequence the whole genome? Or do you have to find more of it?

Dr. RUBIN: Yeah. I think that the group in Leipzig does have enough DNA to get a very rough draft of the human genome. And the German government is supporting a big effort over the next few years to do that. And we're at the same time trying to begin the process of collecting several different samples.

And our hope is to be able to get material from several Neanderthals and take other kinds of approaches we're able to reach in and pull out specific sequences that we're interested in several different Neanderthals and be able to both feel confident that the sequence we're seeing is authentic based its appearance in several Neanderthals as well as be able to look at specific genes that we're interested and not doing whole genome sequencing but rather more targeted approaches.

FLATOW: Let me see if we can get a quick phone call in before we have to go. John in San Rafael. Hi. Welcome to SCIENCE FRIDAY.

JOHN (Caller): Hi, it's a great discussion. My question is isn't too much attention being paid to Neanderthal? Isn't Neanderthal, nothing more than a European variant of advanced Homo erectus? And when I say European, I mean - I'm going from the Shanidar specimen up to…

FLATOW: John. John, I got about minute left. You got to make your question and not give us a lecture on this.

JOHN: Well, that's my question. I mean there's talk about interbreeding with Neanderthals. Advanced humans dispersed from East Africa 100,000 or so years ago, isn't there…

FLATOW: Let me get an answer.

Dr. RUBIN: It's a practical response…

FLATOW: Go ahead, Richard. Eddie, go ahead.

Dr. RUBIN: Yeah. I'll give you a practical response in that getting DNA from a 40,000-year-old specimen is really pushing the limits. And so, to think about going to erector samples that are hundreds of thousands of years, I think that's, you know, right now seems beyond the limits. And so that's one practical reason.

Also we're interested in our most recent common ancestor, our first cousins. And I think Neanderthal fits it for that bill. And so I think that's part of the reasons why we're so interested in Neanderthals.

FLATOW: Richard, would you agree?

Mr. KLEIN: Well, there is the possibility, I suppose - and Dr. Rubin should comment on this - of finding 40, 50 thousand-year-old non-modern fossils in East Asia. No one's really tried very hard to do that at this point. But ones that might retain DNA - and, sure, they will not be Neanderthals. They'll be another kind of non-modern people and we'd also like to know how they differed genetically from ourselves and from the Neanderthals.

Dr. RUBIN: I agree.

FLATOW: Well, that was my last question. Is everybody going to go now back through their bones knowing that what couldn't be done can be done, possibly?

Dr. RUBIN: Yeah. I think that a few years ago that you wouldn't have thought that getting Neanderthal nuclear DNA was possible. And it's clearly possible and I think it's likely we're going to have the whole genome soon. And so, you know, who knows what the edge is -what's possible? Particularly connected to new technologies and new sequencing technologies that allow us to drive thousand-folds and million-folds more data than we used to be able to do.

FLATOW: So, do you continue now trying to finish up this sequence?

Dr. RUBIN: Well, I think that the German group is going to finish the sequence of this particular bone. And we're developing technologies to try to make it less destructive where we have to destroy less bone as well as collecting samples from several specimens.

FLATOW: Richard Klein, where do you think this is headed?

Mr. KLEIN: I think that it will resolve some very important issues in paleoanthropology. I think the public often thinks that paleoanthropologists are prima donnas who just like to argue endlessly among themselves and they never resolve issues. The genetics is going to resolve a lot of important issues for us, including this issue of whether these archaic kinds of people, at least that lived in Eurasia, the Neanderthals in particular, contributed in any way to us. And, again, why they're gone.

Dr. RUBIN: You know, I think in addition it will change the field in some ways. And this is a little bit what Ira earlier. In that it is a fairly data-poor field that is based on a limited number of skeletal remains and associate artifacts that are frequently hard to access by curators in far away places.

And all the data that's being generated over sequence data is all freely available on the Web. And so, in the future I think scientists and geneticists and anthropologists will be able to sit at their terminals and access this and…

FLATOW: I've got to take a break. Gentlemen, stay with us through the break. We'll be right back to talk lots more with Richard Klein, Eddie Rubin and see if we can get a question or two from you folks out on the phones. So stay with us. We'll be right back.

I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.

(Soundbite of music)

FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.

We're talking this hour about Neanderthals and papers written in Nature and Science Magazine. In fact, one of the News and Views comments in Nature said that these papers are perhaps the most significant contributions published in this field since the discovery of Neanderthals 150 years ago.

Our number: 1-800-989-8255. What's the right way to say that name? Is it Neanderthals or Neandertals or could it be said either way?

Mr. KLEIN: Well, I'm giving my answer. And initially when they were discovered, the first Neanderthal fossil to be recognized from what it was came from a place called the Neander Valley near Düsseldorf, Germany. Valley, in German at the time, was spelled T-H-A-L. Later on there was a spelling change and the H was dropped. However, I think that with or without the H - and some people use the H today and some people don't, that is some specialist - I think you would say it Neandertal rather than Neanderthal. But I don't think it matters a whole lot.

FLATOW: Let me see if I can get a phone call or two before we have to go. Let's go to Anita in Sunnyvale, California. Hi, Anita.

ANITA (Caller): Hi. I have two very quick questions. Number one, what is the mutation rate that you're using to estimate the 700,000 and 400,000 mark of the split? And number two, do you think you can get any DNA from the Portuguese boy who is supposedly a hybrid? And I'll take the answer off the air. Thank you.

Dr. RUBIN: And so the way that the split is calculated, the divergence time is when they come back to a common ancestor. And that is basically looking at the number of variations that we see between the human, Neanderthal and chimp genome. And from that you eventually - and it assumes a, you know, the chimp having diverged from Neanderthals and Homo sapiens 5 to 8 million years ago.

And so it looks at the sequence that leads to the common ancestor. And it also takes in models of populations. So it's a complex calculation. In a similar way, the split time looks at the estimated population sizes as well as looks at variations that occur within humans as well as the variations that derived and ancestrally that we see in the Neanderthal sequence.

And so, I guess this is a short answer to a very long question. And the second one was getting material from - yeah, I think that one would like to get material from all these samples. And I think the one that was referred is one of the issues of there being a hybrid between Neanderthal and Homo sapien features, thinking that this was a transitional state.

And sure, getting sequence from that would help address the issue, whether it's just an abnormality in structure or whether it really indeed represents a transition.

FLATOW: Well, gentlemen, I want to thank you for taking time to talk with us today. Richard Klein, paleoanthropologist at Stanford University, and Eddie Rubin, director of the Department of Energy's Joint Genome Institute in Walnut Creek, California. Thanks, and have a good weekend to both of you.

Mr. KLEIN: Okay.

Dr. RUBIN: Thank you very much.

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