Searching for answers to human ancestors in very old DNA

Searching for answers to human ancestors in very old DNA

As he puts it in the subtitle of his memoir, ‘Neanderthal Man,’ Svante Paabo goes in search of lost genomes.

Dr Paabo, a 59-year-old Swede who leads his own laboratory at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, was the first to extract and sequence the genomes of the ancient humans called Neanderthals and Denisovans, and to compare them with those of modern humans. Genes, and the stories they tell, are texts he reads. He was recenly interviewed by Claudia Dreifus for three hours in Washington.

Excerpts:  Did you always want to be a geneticist?

I wouldn’t say so. When I was 13, my mother took me to Egypt. That made a big impression; afterward I thought I might become an Egyptian archaeologist. I had a very romantic idea what that would be like: discovering mummies and pyramids and things like that. I even started studying Egyptology at the university. But there, my romantic ideas caught up with reality. In the 1970s, Swedish Egyptology was very linguistically oriented. It was about ancient word forms and translating hieroglyphics. I couldn’t imagine spending my life with it.

How did you come to invest an antirely new research aras, the genetics of ancient humans?

In the late 1970s, while I was doing my medical studies (at Uppsala University in Sweden), these new techniques for studying DNA were introduced — cloning, sequencing. I was amazed by them and learned how to do them. And that brought me to thinking again about Egyptian antiquities. I knew that there are hundreds of mummies stored in museums across Europe. Mummies, after all, are the dried-out bodies of dead people or animals. I wondered if in some, their DNA might still be preserved. If it was present, we could study it just as we study the DNA of people alive today. My thought was, “If we could do this, we can answer many questions in history that we cannot otherwise answer.”

Such as?

Are the people who built the pyramids the direct ancestors of the people who live in Egypt today? Or, When the Neanderthals encountered modern humans, did they mix? But to do this, one needed to obtain DNA that might be preserved in those ancient human remains. In the 1970s, many people thought that DNA was so sensitive a molecule that it probably degraded within hours of death. I thought I should test that idea. So I bought a piece of calf’s liver and dried it in an oven.

 The DNA survived!

Encouraged, I went on to test for DNA in some Egyptian mummies kept in our small museum in Uppsala. However, I couldn’t find any DNA in a single one. Eventually, my Egyptology professor, who had some contacts in what was then East Germany, arranged for me to go to the Bode Museum to collect samples from their large collection of mummies. Back in Uppsala, I studied the samples from the Bode mummies under a microscope, always searching for the remains of a cell nucleus. This is a part of the cell where the genome is located. After a few weeks, I detected a cell nucleus that appeared to contain preserved DNA. This was so encouraging.

In 2010 your research group sequenced the Neanderthal’s genome? Did it show that the groups had mixed?

When we compared the Neanderthal genome to the genes of today’s humans, it showed they had. If your ancestry is from Europe or Asia, 1 to 2 per cent of your DNA comes from Neanderthals. Sub-Saharan Africans don’t have Neanderthal genes because the Neanderthals never were there.

Your laboratory identified a new group of extinct humans. How did you come discover them?

Some Russian colleagues sent us a tiny little bone fragment they’d found in a southern Siberian cave two years earlier. At first I thought it was a Neanderthal or a modern human. Yet as we began to sequence its DNA, it became clear it was neither. Soon we saw that the ancestors of this child, a girl, had a common ancestor with Neanderthals. It went back very far, though — at least 200,000 years. We also saw that her group had a long history independent of the Neanderthals. So now it was clear: we were working on the genome of a human group that wasn’t known before. This was the first time a new form of extinct human had been described from genome sequences and not fossil bones. We named them Denisovans, after the Denisova Cave, where the bone had been found.

How do you think that happened?

Beyond what the genome says, one can’t know. The easiest explanation is that when modern humans came through South Asia, they encountered Denisovans, bred with them and continued migrating.

Will there be more human groups discovered in the next few years?

Had you asked me this before the Denisovans, I would said, “Nah, we pretty much know what’s there.” But now I feel there is a lot more to be discovered. In particular, we need to look more in China. It’s unclear how the humans who lived in China 50,000 to 100,00 years ago relate to the Denisovans and Neanderthals. So China is a very important place. But there are interesting things in Europe too. In Spain, there’ve been some very important discoveries with 400,000-year-old Homo heidelbergensis. We are very excited that we’ve been able to get some DNA from one of the fossils there.

Do you ever reflect on your adventurous career? You grew up to become Indiana Jones, after all...

Yes, it has so much exceeded my wildest dreams. Rather than be the archaeologist, I ended up studying history in a new way.