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.

Complicating the Family Tree

Our view of our past keeps getting more complicated. Our family tree, it turns out, is more of a twisted vine than a neatly linear branch.

Evidence keeps building by the day that our anatomically modern human (AMH) ancestors interbred with earlier forms of “archaic” humans. In the 31 Oct 2011 early online issue of PNAS, Pontus Skoglund and Mattias Jakobsson present evidence for the view that the genetic legacy of the Denisovans is wider than ever thought before.

First is was the Neandertals. This branch of the human family diverged from our own somewhere around 500,000 years ago. Somewhere between 100,000 and just 50,000 years ago, however, AMHs and Neandertals interbred successfully. The result lives on today in our genes. For many of us, our DNA is 2-3% from our Neanderthal ancestors. The Neandertals may be extinct, but their DNA lives on in every cell in the human body.

Then it was the Denisovans, a recently discovered branch of the human family more closely related to Neandertals than to us. What about AMH-Denisovan iInterbreeding? An international team of researchers led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig was able to extract Denisovan DNA from tiny fragments of remains. From the extracts, they reconstructed the Denisovan genome and compared it with the human genome. What they found was clear evidence of interbreeding. Some living human beings—those identified as Melanesians—carry Denisovan genes. That was reported in December 2010.

In September, however, Pääbo was joined by David Reich and Mark Stoneking and other colleagues in reporting that the legacy of Denisovan DNA extends beyond the Melanesians. It’s all over the islands that extend below Southeast Asia, including Australia. Not just Aboriginal Australians but Near Oceanians, Polynesians, Fijians, east Indonesians, and other groups as far as the Philippines are carriers of the Denisovan legacy.

According to this study, the genetic legacy of AMH-Denisovan admixture does not include East Asians. This led the authors to conjecture that there are at least two main waves of AMH migration into southeast Asia. The first wave interbred with Denisovans while the second, apparently, did not.

Their work appeared in the 7 Oct 2011 issue of the American Journal of Human Genetics. Reich discusses these findings in a video. Hint: start at minute 22:30.

But now a study published in the online early edition of the Proceedings of the National Academy of Sciences for the week of 31 Oct 2011 presents evidence that East Asians are also descended in part from the Denisovans. In the paper, the authors (Pontus Skoglund and Mattias Jakobsson) write that “we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome.”

Experts in the field will no doubt debate these findings. Just how widespread is the effect of AMH-Denisovan interbreeding? How widely did AMHs and archaic humans interbreed? To what extent does admixture provide any benefit? Does it shed any light on observable differences between different groups within the human family today?

According to Skoglund and Jakobsson, the “history of anatomically modern and archaic humans might be more complex than previously proposed.”

If our past is more complex than we thought, so is our present. What does it mean to be human? It no longer seems to mean that we are all part of a biological species. Whether we like to call ourselves "anatomically modern humans" (AMHs) or Homo sapiens, we are learning that the very concept of species is becoming unfocused by research. Should we speak of AMH-Denisovan "interbreeding" or "hybridization"? Does it matter? Are we separate species or one slightly-tangled humanity?

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.