We, the human being, have always been fascinated by our own origin. For Swedish researcher Svante Pääbo, this fascination has led all the way to the 2022 Nobel Prize in Physiology or Medicine, which he has been awarded for his work in mapping Neanderthal genomes. His discoveries show, among other things, that today’s humans have more in common with our extinct relatives than we previously thought and are an important piece in our genetic puzzle. The work has also led to the discovery of a previously completely unknown human species.
Svante Pääbo will be the ninth Swede to receive the prestigious Nobel Prize in Physiology or Medicine. He also adds a second Nobel Prize to the family’s collection, after his father Sune Bergström who was awarded the prize in 1982, together with Bengt Samuelsson and the Brit John R. Vane.
Pääbo’s journey through human genetic history began when, alongside his doctoral studies, he worked to isolate DNA from a 2 400-year-old mummy. As a postdoctoral fellow of the eminent evolutionary biologist Allan Wilson, he began a several decades long effort to develop methods to make it possible to analyse the DNA of Neanderthals.
Started with analysing mitochondria
A major problem that Pääbo faced was the fact that DNA changes over time and breaks down into ever shorter fragments. After thousands of years, there is only very little DNA left in human remains and these are often mixed up with a large amount of DNA from bacteria and modern humans.
As a professor at the University of Munich, Pääbo continued the work and decided to start by analysing ancient DNA from Neanderthal mitochondria. The genome of the mitochondria contains a very small part of the cell’s genetic information, but on the other hand it is found in thousands of copies, which increases the chances of success. With the help of new methods, Pääbo finally managed to sequence a region of mitochondrial DNA from a 40 000-year-old piece of bone.
Was able to analyse the cell core with improved methods
The next step was to sequence Neanderthals’ genome from the cell core, where the majority of the genome is found. At the newly founded Max Planck Institute in Leipzig – where Pääbo himself is one of the founders – he and his group were able to, step by step, improve the methods for isolating and analysing DNA from very old bone finds. The work finally yielded results and in 2010 the group had succeeded in mapping the Neanderthals’ DNA sequence.
This has allowed detailed analysis on the kinship between Homo sapiens and the Neanderthals. One of the discoveries from that analysis is that people from Europe and Asia have much more in common with Neanderthals than humans from Africa. It has been shown that Homo sapiens and Neanderthals conceived children together during the thousands of years that we lived together. Modern humans originating from Europe and Asia have a an average of 1 to 4 per cent of their genome stemming from the Neanderthals.
New species discovered
But that is not all. In 2008, an approximately 40 000-year-old piece of bone was discovered in the Denisova Cave in southern Siberia. After analysing the bone, Pääbo and his research team were able to conclude that they had discovered a whole new human species, denisova. Further analyses showed that ethnic groups in Melanesia and Southeast Asia today carry up to 6 per cent Denisova DNA.
What makes us unique?
The discoveries have given researchers a new understanding of humanity’s evolutionary history and established a whole new field of research, paleogenomics. After the initial discoveries, Pääbo and his group have continued the mapping, and over the years they have been able to add several genomes from extinct human species.
The genetic differences between Homo sapiens and our extinct relatives were completely unknown to the scientific community before the discoveries of Pääbo and his team. Intensive work is now underway to try to understand the significance of all these differences, with the goal of reaching an explanation as to what it is that makes today’s human being uniquely human.