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Vol. LXVI, No. 11
May 23, 2014
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‘Humans, Neanderthals Kissing Cousins?’
Archaic Genomics Adds Detail to History of Humanity

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Dr. Svante Pääbo
Dr. Svante Pääbo
Once upon a time, a Swedish scientist named Dr. Svante Pääbo was fascinated with the history of ancient peoples. Besides becoming an esteemed paleontologist, Pääbo also grew into something of a scientific storyteller, recounting a 500,000-year-old narrative over the course of a three-decades-long career in genomics. He continues to tap archaic DNA to add rich detail to the story.

Now director of the Max Planck Institute for Evolutionary Anthropology and a founder of paleogenetics, Pääbo is “truly an authority on the study of ancient DNA,” said NHGRI director Dr. Eric Green. NHGRI hosted Pääbo’s recent lecture at NIH, “The Neanderthal and Denisovan Genomes.”

Who Were the Earliest People?

Pääbo divided his talk into three parts: technical aspects of retrieving ancient DNA and sequencing ancient genomes; what we’ve learned from studying the genes of our closest extinct relatives; and “where we go from here—how we can use these genomes to try to get to functional differences between us and other organisms.”

Continued...

The storyteller began by offering the basic, most recent African-origin model of the emergence of contemporary humans.

“Modern humans evolved in Africa, accumulated variation there and a part of that variation went out and colonized the rest of the world” an estimated 100,000 years ago or less, Pääbo said. “There is a problem with that model, however. A hundred thousand years ago there were many other forms of humans around, most famously the Neanderthals in Europe and, in Asia, other less well-described forms of humans.”

slideof the reconstructed skeleton of a Neanderthal compared to a present-day human Pääbo described the extinct group as “a robust form of hominids.” The Neanderthal population appears to have been physically stronger and hardier than contemporary humans. Researchers surmise that these earlier people were better suited physique-wise to survive colder climes than we are today. In addition, they had larger cranial capacity than we do.

Showing a slide (l) of the reconstructed skeleton of a Neanderthal compared to a present-day human, Pääbo described the extinct group as “a robust form of hominids.” The Neanderthal population appears to have been physically stronger and hardier than contemporary humans. Researchers surmise that these earlier people were better suited physique-wise to survive colder climes than we are today. In addition, they had larger cranial capacity than we do.

Photos: Bill Branson Slide Images: Svante Pääbo

Showing a slide of the reconstructed skeleton of a Neanderthal compared to a present-day human, Pääbo described the extinct group as “a robust form of hominids” that appeared in the fossil record about 400,000 years ago and disappeared about 30,000 years ago.

The Neanderthal population appears to have been physically stronger and hardier than contemporary humans. Researchers surmise that these earlier people were better suited physique-wise to survive colder climes than we are today. In addition, they had larger cranial capacity than we do.

Tale of Two Theories

For some time, Pääbo said, “there have been two major ideas in paleontology about how modern humans relate to Neanderthals and other extinct forms when they come out of Africa.”

One model—called “total replacement”—holds that modern humans evolved in Africa and left the region without ever mixing with any other hominid, effectively superseding the other forms. The other model agrees that there was replacement but allows that there was also most likely some interbreeding among early human forms after the exodus from Africa into areas of Europe and Asia, where modern humans then gradually picked up genetic variations and ultimately evolved.

Pääbo said the first chance to test the ideas genetically came in the mid-1990s when scientists gained access to “not just any Neanderthal, but ‘The Neanderthal’ [from Neander Valley, Germany] that was found in 1856 and gave its name to this group of hominids…It was actually the first time we realized there had been other forms of humans here besides present-day humans.”

Using PCR and other technologies of the time, DNA studies in the 90s focused on the mitochondrial genome (mtDNA).

“It’s quite clear that there are no people walking around on the planet today with the mitochondrial genome from Neanderthals,” Pääbo said of his findings released in 1997. The total replacement model held up.

“We learned something else from those studies as well,” he noted. “Neanderthals cannot be very different from us.” Modern humans shared a common ancestor with Neanderthals about half a million years ago or later.

High-Throughput a Game-Changer

Then, along comes high-throughput DNA sequencing, which transformed the field. Pääbo and his team received funding to sequence a draft of the entire Neanderthal genome, which they worked on from 2005 to 2010 using bones from three different individuals found in a Croatian cave. In 2009, the team collaborated with Dr. Jim Mullikin, director of NIH’s Intramural Sequencing Center at NHGRI.

The best Neanderthal bones have 4 percent endogenous DNA; 70 percent endogenous DNA was extracted from a child’s pinky bone found in the Denisova Cave. The bone part was about one-quarter the size of a penny, as shown in this slide image.
The best Neanderthal bones have 4 percent endogenous DNA; 70 percent endogenous DNA was extracted from a child’s pinky bone found in the Denisova Cave. The bone part was about one-quarter the size of a penny, as shown in this slide image.

One of the first—and most controversial—questions Pääbo tackled with the new capabilities was, what happened when modern humans exited Africa and met Neanderthals? Did they mix or not?

“We went about it several different ways,” Pääbo confided, “because there are wars in paleontology about this and I had the feeling we had to get it really right.”

His group started with a premise: “If there was a contribution from Neanderthals to people in Europe, [then] we would expect people in Europe to share more alleles with Neanderthals than with people in Africa, where there have never been Neanderthals.”

Scientists tested 5 different sample genomes: 1 European, 2 Africans, 1 from Papua New Guinea and 1 from China.

Hello, Cousins?

The results were unexpected: The Neanderthal shared a similar number of alleles with the genomes from places where Neanderthals had never lived.

“This was very surprising to us at the time, because if we would see a contribution we would have expected it in Europe, where Neanderthals have lived, not in Papua New Guinea and China.”

Pääbo’s explanation? “When modern humans came out of Africa between 50,000 and 100,000 years ago they presumably passed by the Middle East and we know Neanderthals lived there. So those modern humans mixed with Neanderthals and then became the ancestors of everybody outside Africa.

They carried with them this Neanderthal contribution out into the world to the extent that people outside Africa have something between 1 and 2 percent of their genome from Neanderthals.”

A Little DNA Goes a Long Way

In 2010, using DNA from a bone fragment found in a cave, Pääbo identified a newly discovered extinct species predating modern humans, the Denisovan. “It was the first time an extinct group of human was described just from a genome species,” he said. “We have improved our methods quite dramatically for retrieving small amounts of damaged DNA.”

The best Neanderthal bones have 4 percent endogenous DNA; 70 percent endogenous DNA was extracted from a child’s pinky bone found in the Denisova Cave in southern Siberia, where China, Kazakhstan, Mongolia and Russia meet. The bone part was about one-quarter the size of a penny.

NIH director Dr. Francis Collins (l) and NHGRI director Dr. Eric Green (r) join Pääbo in Masur as he reunites with 2009 collaborator Dr. Jim Mullikin of NIH’s Intramural Sequencing Center.
NIH director Dr. Francis Collins (l) and NHGRI director Dr. Eric Green (r) join Pääbo in Masur as he reunites with 2009 collaborator Dr. Jim Mullikin of NIH’s Intramural Sequencing Center.

“So I think this is a good indication of what will happen much more in archeology in the future,” Pääbo suggested. “From tiny little bones, you can reconstruct a lot of the population history of individuals you find, but [it is] very frustrating [that] you have no idea how the skeleton of this individual looked, what stone tools they made, et cetera.”

Pääbo recounted the probable emergence of Neanderthals and Denisovans, according to genomic data. “[About 500,000 years ago] we think they have an origin in Africa, migrated out of Africa and evolved in western Eurasia to Neanderthals and eastern Eurasia to Denisovans,” he said. “Then modern humans emerge in Africa, come out of Africa and mix with Neanderthals presumably in the Middle East and around 50,000 years ago start spreading seriously over the world. They mix once more with Neanderthals—perhaps in central Asia—and they mix with Denisovans somewhere in southeast Asia and continue out into the Pacific. Then these forms [Neanderthals and Denisovans] become extinct, but they live on a little bit in people today.”

‘Total Replacement’ Idea Has Holes

"So, we’ve clearly rejected the notion of total replacement,” Pääbo concluded. “We have contributions from these extinct forms, but the major picture is of an exodus out of Africa. Most of our variation comes out of Africa.”

He coined a term for this new picture of evolution, “leaky replacement.”

“There is replacement,” he explained, “but a bit of genetic contribution from these other forms.

“All these human groups have mixed with each other, but generally it’s mixture of low magnitude. We have always mixed at least a little.”

Next Chapter More Challenging

What intrigues Pääbo most for future research, he said, is how to use genomics to discover changes that led to functional differences between extinct peoples and us. Stone tools and technology among the whole range of extinct populations were fairly identical and changed little over time, he explained, until contemporary people arrived.

“When modern humans come, all that changes,” Pääbo said. “Technology starts changing rapidly and becomes regionalized.” People in different areas start making different tools. “We have existed only about a third of the time that Neanderthals existed on the planet and…we can all agree that our technology today is quite different than 50,000 years ago.”

You can view Pääbo’s entire hour-long NIH talk on NHGRI’s channel at www.youtube.com/watch?v=M7VdRKQuAa8.


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