Human-Neandertal Interbreeding: When and Where?

Comparison between Neandertal and anatomically modern human genomes shows a history of interbreeding. Some living human beings—those with ancestry in Europe and Asia—carry the results of that interbreeding in their DNA. Those with ancestry in sub-Saharan Africa typically do not.

We also know that Neandertals lived in Eurasia from 230,000 until about 30,000 years ago. Where they came from or why they disappeared remains an open question. And we know that anatomically modern humans first appear in Africa at least 200,000 years ago. Some of them made their way to Asia and Europe sometime in the last 100,000 years.

So when did modern human/Neandertal interbreeding last occur? Did it occur deep in our past, before modern humans and Neandertal ancestors left Africa? Or did it occur after both left Africa, sometime—in other words—within the past 100,000 years?

A new study claims to find evidence that the interbreeding occurred out of Africa. Researchers argue that on the basis careful analysis of the shared DNA, the most recent interbreeding occurred sometime between 37,000 and 86,000 years ago.

Caption: Reconstruction of a Neandertal, 2006, by Stefan Scheer, from Stefanie Krull, Neanderthal Museum Picture Library, Mettmann, Germany

If so, it is pretty strong evidence that the interbreeding occurred after anatomically modern human left Africa. This may have occurred in the Middle East, researchers point out, but probably not just at the beginning of the modern human migration out of Africa. The most recent interbreeding, they conclude, occurs well after this 100,000 date, suggesting ”a more recent period, possibly when modern humans carrying Upper Paleolithic technologies expanded out of Africa.”

In that case, the conceptual challenge posed by the modern human/Neandertal interbreedng remains clearly in front of us. What is the human species? Were Neandertals human? And what are we to make of our new insight into modern human diversity. All puzzling questions, to put it mildly.

The article, "The Date of Interbreeding between Neandertals and Modern Humans," is published in the current issue of PLOS Genetics, where it is available free to the public.

Denisovan DNA in Focus

Using new techniques to study ancient DNA, scientists have unraveled the genetic details of a young girl who lived in central Asia around 50,000 years ago. She is the only individual of her kind, a unique branch of the human family called the Denisovans, named for the cave where her remains were found in 2008.

What makes the research all the more startling is that only two teeth and one pea-size bone fragment has been found. But from those tiny fragments of humanity, the story of the Denisovans is being pieced together.

The new techniques were developed by Matthias Meyer, working at the Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology in Leipzig, a research program led by Svante Pääbo. DNA extracted from the bone fragment was separated into two strands that were amplified and analyzed separately, many times over, until a highly reliable sequence was determined.

Laboratory for the extraction of ancient DNA. [Image courtesy of Max Planck Institute for Evolutionary Anthropology].

Researchers claim that the result is as complete and accurate as the sequence of living human beings. Already, the new technique is being used to study other ancient remains, including samples of Neandertal DNA. Denisovans and Neandertals, distinct but closely related forms of humanity, overlapped with anatomically modern humans (AMH) and interbred with them.

New methods in genetics, including the technical breakthrough described in this paper, are opening new windows on the human family tree, which resembles an inter-grown vine more than a straight line of branches.

So accurate is the genetic analysis that researchers can reach some conclusions about other Denisovans, even though no samples exist for them. For one thing, despite their wide geographic spread, they apparently never reached high numbers. Their DNA lives on today in the faint echo of ancient interbreeding found in the uniquely-Denisovan sequences carried by those who live in the islands of southeast Asia.

No one knows what Denisovans looked like, but they probably resembled us in many ways. The Denisovan girl whose DNA was studied carried genes that are associated today with brown hair, brown eyes, and dark skin. Like us they had 23 pairs of chromosomes (compared to chimps with 24), making interbreeding more readily possible.

Denisova molar, distal. [Image courtesy of Max Planck Institute for Evolutionary Anthropology].

One of the more tantalizing aspects of the report is the light it sheds not on the Denisovans or the Neandertals but on us anatomically modern human beings who live today. Why did we survive and flourish culturally when they did not?

One explanation may lie in the genetic differences between us and them, which can be studied for the first time in detail. In this paper, researchers identify specific changes in genes that are associated with brain complexity, synaptic connections, and speech development. According to the paper, “it is thus tempting to speculate that crucial aspects of synaptic transmission may have changed in modern humans.” In other words, tiny differences in DNA led to still relatively small differences in brain function that led to huge differences in culture.

Future technical advances will continue to shed new light on the complex story of recent human ancestry. By gaining ever-higher clarity on the genetic differences between Neandertals, Denisovans, and modern humans, we will come to know the story of our humanity in greater detail.

The paper ends with this reflection: “This [work] should ultimately aid in determining how it was that modern humans came to expand dramatically in population size as well as culturally complexity which archaic humans eventually dwindled in numbers and became physically extinct.” The paper, “A High-Coverage Genome Sequence from an Archaic Denisovan Individual,” is published in the 30 August 2012 issue of Science, published by the American Association for the Advancement of Science.

Neandertal Medicine

Neandertals not only ate their vegetables. They used specific plants—even ones that tasted bitter—to treat their ailments. That’s the latest finding from the international team of researchers studying Neandertal remains at in El Sidrón archeological site in northern Spain. Discovered in 1994, El Sidrón has yielded thousands of samples from at least 13 Neandertal individuals.

Using newer techniques of microanalysis, the team studied the dental plaque recovered from teeth of five individuals dating about 50,000 years ago. Lodged in the plaque were tiny microfossil remains of various plants, providing evidence that Neandertals supplemented their diet of meat with a wide range of grain, herbs, and vegetables. The study is published this week in Naturwissenschaften (The Science of Nature).

CAPTION: Researchers working in El Sidrón Cave. Credit: CSIC Comunicación.

"The varied use of plants we identified suggests that the Neanderthal occupants of El Sidrón had a sophisticated knowledge of their natural surroundings which included the ability to select and use certain plants for their nutritional value and for self-medication. While meat was clearly important, our research points to an even more complex diet than has previously been supposed," according to Karen Hardy, a leader in the research team, according to a press release from the University of York.

Neandertals disappeared from Europe and Asia somewhere around 30,000 years ago, often sharing regions with modern humans for thousands of years. Only recently has it become clear that they depended heavily on plants as well as meat for their food.

"The evidence indicating this individual was eating bitter-tasting plants such as yarrow and camomile with little nutritional value is surprising. We know that Neanderthals would find these plants bitter, so it is likely these plants must have been selected for reasons other than taste," said Dr Stephen Buckley, a member of the research team.

The clear implication of the study—that Neandertals recognized the medicinal value of certain plants—provides further evidence of the sophistication of Neanderthal culture and technology. The full scope of Neandertal cultural interaction with modern humans remains an open question.

"El Sidrón has allowed us to banish many of the preconceptions we had of Neanderthals. Thanks to previous studies, we know that they looked after the sick, buried their dead and decorated their bodies. Now another dimension has been added relating to their diet and self-medication," according to Antonio Rosas, also on the research team.

CAPTION: Microscopically visible material entrapped in dental calculus samples – filamentous and cocci bacteria. Credit: Karen Hardy/Naturwissenschaften.

The article, "Neanderthal medics? Evidence for food, cooking and medicinal plants entrapped in dental calculus," is published in the current issue of Naturwissenschafen.

Human Nature, Human Self-Creation

When I spoke at the University of South Florida-St Petersburg last week, I summarized various ways in which the Human Genome Project has opened new perspectives on recent human evolution.

Evidence is mounting the anatomically modern humans (AMH) interbred with archaic humans, such as Neandertals, within the past 80,000 years and perhaps as recently as 30,000 years ago. Not only that, but in the view of some experts, this interbreeding was widespread, possibly more the rule than the exception.

The title of my talk was “Finding the Human in the Genome.” I presented visual images of early human art, including the recent report of the discovery of the 100,000 “artist workshop” in South Africa.

Looking at ancient art can be inspiring and moving, but for us today, the question comes back more forcefully than ever. What are we? Where are we going as a species? Are we in danger of destroying ourselves, not by violence but by modification, by engineering future humans that are not exactly human anymore?

I suggested that our past is somewhat more complex than we thought. Our future, likewise, is a bit more open-ended. We are not clearly defined at either end, either in our origins or in our destiny. As science discovers a complex past, technology opens an uncharted future.

At that point in the talk, I turned to the prescient words of Giovanni Pico della Mirandola, the author of the Oration on the Dignity of Man. Writing in 1486, Pico praises the greatness of the Creator, the “Great Artisan,” who creates human beings with no defined or determinate nature, except the need for self-creation:

Finally, the Great Artisan mandated that this creature who would receive nothing proper to himself shall have joint possession of whatever nature had been given to any other creature. He made man a creature of indeterminate and indifferent nature, and, placing him in the middle of the world, said to him "Adam, we give you no fixed place to live, no form that is peculiar to you, nor any function that is yours alone. According to your desires and judgment, you will have and possess whatever place to live, whatever form, and whatever functions you yourself choose. All other things have a limited and fixed nature prescribed and bounded by our laws. You, with no limit or no bound, may choose for yourself the limits and bounds of your nature. We have placed you at the world's center so that you may survey everything else in the world. We have made you neither of heavenly nor of earthly stuff, neither mortal nor immortal, so that with free choice and dignity, you may fashion yourself into whatever form you choose. To you is granted the power of degrading yourself into the lower forms of life, the beasts, and to you is granted the power, contained in your intellect and judgment, to be reborn into the higher forms, the divine.

According to Pico, God speaks these words to the newly created Adam and Eve and, in effect, to all of us. Then Pico comments: “Imagine! The great generosity of God! The happiness of man! To man it is allowed to be whatever he chooses to be!”

Now, thanks in part to recent science, we can see just how far Pico was right.

Archaic Interbreeding? So What?

Later this week, I will be speaking at the University of South Florida—Saint Petersburg in their lecture series, a Celebration of the Genome.” My topic is “Finding the Human in the Genome.”

I start with the obvious: Our knowledge of human biology is increasing rapidly, thanks in large part to the Human Genome Project. We can now compare the DNA of one human being with another and ask questions about similarities and differences. We can compare human DNA with the full genomes of chimps and other species.

Most interesting to me is that we can also compare the genome of anatomically modern humans with that of extinct forms of humanity, such as Neandertals or their recently discovered cousins, the Denisovans. What we have found is that in a real sense, they are not extinct at all because their DNA lives on in us.

That leads to something less obvious but more profound. The more we know about human biology, the less we know about human nature. Put another way, the more information we have, the less confident we are that we really know what we mean when we talk about “humanity.”

So what is going on here? Does it really bother anyone—besides me, that is, and perhaps only because I am, after all, a “theologian”? I am asking myself this question a lot these days. Does it really matter that our ancestors interbred with Neandertals and Denisovans and, as time will probably tell, many other forms of archaic humanity?

So what’s the big deal? In some ways I guess it’s like the high school student who runs a paternity test and learns that daddy isn’t daddy.

Or maybe it’s more like this. Years ago, I remember hearing Kári Stefánsson speaking to a roomful of scientists and introducing deCODE Genetics, the Iceland DNA database. He explained the reasons for the project, such as excellent health records, small genetic diversity, and superb genealogical records going back 1,000 years. We Icelanders need to sell more than fish, he said. We want to mine our DNA for all kinds of gene-disease information. Then Stefánsson mentioned that the information sometimes disproved the genealogies. Everyone laughed when he said: “We are not responsible for what our Viking ancestors did back then during the long Icelandic winters.”

Is that it? Is that all that’s happened here, just some forced revisions of the family tree? So what if my ancient ancestors were not exactly what I thought? It happened, after all, some 40,000-100,000 years ago. I am not responsible.

But I am affected. My biology is different from what I once thought. Perhaps I am healthier as a result of the ancient interbreeding, as at least one report has suggested.

More than that, I am coming to see human beings as biologically more diverse and more complicated that we once thought. The diversity part is a bit scary. We have not done well as a species in dealing with our differences.

The complexity part—that’s more of a mystery than a fear. I don’t claim to hear the voices of my Neandertal ancestors calling out from my DNA or reverberating through my metabolic processes. At least not yet.

Still wondering..."What Defines Us?"

Last February the editors of Science marked the 10th anniversary of the publication of the complete human genome. They invited a dozen or so people to contribute short reflections on the meaning of this milestone.

I was given 250 words for my article, entitled “What Defines Us?” In that small space I tried to suggest two things. First I noted a simple irony: As we gain more scientific information about our genome and our evolution, the philosophical and religious concepts of humanity become blurred or defocused. Second, I suggested that this defocusing need not be a cause for discomfort. Precisely because we are humans—whatever exactly that means anymore—we switch almost immediately from discomfort to wonder and excitement. The quick switch is what makes us human. I ended by asking: “Who are we, and where will we go next?”

It is as if we are making ourselves up as we go along. Recent discoveries in human evolution intimate just such a view. Anatomically modern humans are now believed to have interbred with Neandertals and with the more recently discovered Denisovans. Many of us carry the DNA of these extinct forms of humanity in our own genome. In that sense they are not distinct at all but live on in every cell of our bodies. More recently, it has been suggested that similar interbreeding occurred in sub-Saharan Africa.

Interestingly, it has also been suggested that interbreeding enhanced us. In August, a research article in Science suggested that our immune systems are more resilient than they might have been. Why? Because our ancestors interbred with Neandertals and Denisovans.

The evolutionary tree of humanity is beginning to look less like a tree and more like a tangled vine. And now we are led to wonder whether it is the tangle that enhances us. What makes us less clearly Homo sapiens seems, paradoxically, to make us more extraordinary as a species. Well…we’re running far ahead of the science here, but (as I suggested in Science), wondering is what makes us human. It’s not just the DNA; it’s what we dare to do with it.

I have been thinking about this recently because I will be speaking on November 10 on this very topic at the University of South Florida Saint Petersburg. They have planned an exciting lecture series, Festival of the Genome: Celebrating the 10th Anniversary of the Sequencing of the Human Genome, showcasing various perspectives on human genome research.