Geneticist who unmasked lives of ancient humans wins the 2022 Nobel Prize in Physiology or Medicine

Because these GEITP pages have been sharing many of Svante Pääbo’s exciting breakthrough publications — over the past 14 years — we believe it is only appropriate to report on his winning the 2022 Nobel in Physiology or Medicine this past week. 😊 This [below] is a recent summary in the latest issue of Nature.
Svante Pääbo has made stunning discoveries about human evolution using ancient DNA — and his work helped to spawn the competitive field of palaeogenomics.
Svante Pääbo has been awarded a Nobel prize for discoveries about the genomes of extinct hominins and human evolution.

The 2022 Nobel Prize in Physiology or Medicine has been awarded for pioneering studies of human evolution that harnessed precious snippets of DNA found in fossils that are tens of thousands of years old.

The work of Svante Pääbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig, Germany, led to the sequencing of the Neanderthal genome and the discovery of a new group of hominins called the Denisovans, and also spawned the fiercely competitive field of palaeogenomics.

By tracing how genes flowed between ancient hominin populations, researchers have been able to trace these groups’ migrations, as well as the origins of some aspects of modern human physiology, including features of the immune system and mechanisms of adaptation to life at high altitudes.

Pääbo’s Nobel win “is an extraordinary recognition of this field maturing and of what he did in putting together everything that needed to be done to accomplish this miracle, which is getting ancient DNA from human remains”, says David Reich, a population geneticist at Harvard Medical School in Boston, Massachusetts, who worked closely with Pääbo on the Neanderthal genome sequence.

At a press conference following the announcement, Pääbo said that he was still digesting the news, and didn’t initially believe he had won the Nobel when he got the call from Stockholm. He “at first thought it was an elaborate prank developed by people in my group”.

Chris Stringer, a palaeoanthropologist at the Natural History Museum in London, says that Pääbo’s work — including recovery of the oldest ancient human DNA on record, 430,000-year-old sequences from Spain1 — has revolutionized our understanding of the past. “It’s central to human evolutionary studies now,” Stringer says, adding that the Nobel win is “great news”.
Damaged DNA

Pääbo had to develop ways of analysing DNA that had been damaged by thousands of years of exposure to the elements, and contaminated with sequences from microorganisms and modern humans. He and his collaborators then put these techniques to work sequencing the Neanderthal genome, which was published in 20102. This genetic analysis led to the finding that Neanderthals and Homo sapiens interbred, and that 1–4% of the genome of modern humans of European or Asian descent can be traced back to the Neanderthals.

Pääbo’s techniques were also used to identify the origins of a 40,000-year-old finger bone found in a southern Siberian cave in 2008. DNA isolated from the bone indicated that it was from neither Neanderthals nor Homo sapiens, but came from an individual belonging to a new group of hominins3. The group was named the Denisovans, after the cave in which the bone was found. Ancient humans living in Asia interbred with this group, too, and Denisovan DNA can be found in the genomes of billions of people alive today.

During the early years of ancient DNA research — led by Pääbo and other scientists in the 1980s and 1990s — the field was plagued by concerns over contamination from modern human DNA (Pääbo has admitted that DNA he recovered early on from Egyptian mummy remains was probably his own). But, thanks to methods developed in Pääbo’s laboratory, as well as the advent of new sequencing technologies, contamination is no longer the ‘boogeyman’ it once was.

“When I started, we weren’t even sure you could work with ancient human DNA,” says Pontus Skoglund, a palaeogeneticst at the Francis Crick Institute in London. “But now, and I think led by Svante’s department, we have an approach where contamination is really not a major issue anymore.”
Health implications

Pääbo’s work teasing out DNA from Neanderthals, Denisovans and other hominins also has important implications for modern medicine. Although the proportion of the human genome comprised of archaic DNA is small, this material seems to punch above its weight, making an important contribution to the risks of diseases ranging from schizophrenia4 to severe COVID-195. And people living on the Tibetan Plateau can thank Denisovans for gene variants linked to high-altitude adaptation6.

“The fact that a good fraction of the people running around in the world today have DNA from archaic humans like Neanderthals is of important consequence to who we are,” says Reich. “So I think that knowing that and trying to understand the implications of that for health is something that will be with us for the rest of our time as a species.”

With genomes from multiple Neanderthals and Denisovans available, it is now possible to identify uniquely human genes, says Johannes Krause, a palaeogeneticist at MPI-EVA. In September, researchers showed that a gene variant found in humans, but not in Neanderthals or Denisovans, is linked to greater neuronal growth in lab-grown brain organoids7. “We’ve never come so close to understanding what makes humans humans,” Krause says.

Researchers describe Pääbo as intense and driven, but also collegial and generous. His department at the Max Planck Institute for Evolutionary Anthropology has produced a generation of palaeogeneticists who are pushing the field ever further.

Viviane Slon, a palaeogeneticist at Tel Aviv University in Israel who did her PhD under Pääbo’s supervision, says her former mentor has an “uncanny” ability to see the larger picture while remaining laser-focused on details. When Slon was working on remains that turned out to be a first-generation Denisovan–Neanderthal hybrid, the sequence of maternally inherited mitochondrial DNA matched that of a Neanderthal. But, when publishing those results, Pääbo urged Slon to reserve judgment until they had sequenced nuclear DNA inherited from both parents. “He wouldn’t let me write that it’s a Neanderthal because we didn’t know that, and in fact it turned out to be a mixed offspring,” Slon says.

Reich says that working with Pääbo and the team he organized to sequence and analyse the first Neanderthal genome was inspirational. “It was the best consortium ever,” Reich says. “He recognized how special and unique this type of data they were producing was.” This eventually inspired Reich to set up his own ancient DNA laboratory.

Pääbo’s influence on ancient DNA work has been such that it’s hard to imagine where the field would be without him. “He’s the godfather of the field,” says Skoglund.

Nature 610, 16-17 (2022)


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