For a long time, we thought that it was impossible to analyse the genetic material of a species that has been extinct for tens of thousands of years. But you didn’t let that deter you. What was your motivation?
Svante Pääbo: In the 1990s it became possible to determine some DNA sequences of cave bears and other animals that lived at the same time as the Neanderthals. This made it seem plausible that it would also be possible to decode the DNA sequences of Neanderthals, even though DNA decays over time.
Your initial focus was on mitochondrial DNA, which is easier to obtain.
Pääbo: Yes, it was only possible to do that in the 1990s because it has several copies in each cell.
In 2010 your team almost completely decoded the Neanderthal Genome. What ultimately led to success?
Pääbo: Mitochondrial DNA represents only the maternal line of descent and only a small part of the genome. Technological advances, such as high-throughput sequencing and innovative bioinformatics, were crucial. We have also developed methods for working with small amounts of DNA and enriching the DNA. Another challenge was to detect contamination with human DNA and remove it in a targeted manner.
Apparently, early modern humans interbred with Neanderthals after our ancestors migrated out of Africa. Did you find this result surprising?
Pääbo: Yes, after analysing the mitochondrial DNA we tended to think that we would not find any Neanderthal genes in the human genome. However, our results showed us that we were wrong. About two per cent of our genome comes from the Neanderthals, and in Asians the percentage is significantly higher.
You have already achieved everything in terms of honours and success. What continues to motivate you? What would you like to discover?
Pääbo: Our team is currently researching the functional effects of hominid DNA on modern humans in order to understand what advantages and disadvantages it offers. The immune system is of particular interest here, for example.
We are also studying the DNA of the Denisovans, a group of humans related to the Neanderthals. People from Oceania have about four per cent of this DNA in their genome. We want to find out what evolutionary advantages and disadvantages the DNA might have which has been preserved for such a long time. While archaic gene variants can help us in the fight against pathogens, it can also have disadvantages.
We are also particularly interested in gene variants which are involved in cognitive development. We are interested in when and how the variations that distinguish us from Neanderthals came about. I will talk about our efforts to study such variants in the Christmas lecture at the Leopoldina.
Your research has changed our understanding of our origins. What has changed for you since receiving the Nobel Prize?
Pääbo: I have got better at saying “no”. I decline invitations that are not primarily related to our research as politely as possible.
You have been a Member of the Leopoldina since 2001. What does this mean to you?
Pääbo: I appreciate the policy advice issued by the Leopoldina, even though I have never been actively involved in this myself.
The interview was conducted by Hannelore Gießen