New Delhi: Svante Paabo has been awarded the 2022 Nobel Prize in Medicine for his extraordinary discovery which proved modern humans share DNA with extinct relatives Neanderthals and Denisovans. The Swedish scientist provided key insights into our immune system and what makes us unique compared with our extinct cousins.
Svante Paabo is the son of Sune Bergstrom, who won the Nobel prize in medicine in 1982.
Announcing the award, the Nobel committee said that the scientists sequenced the genome of the Neanderthal, an extinct relative of present-day humans, and made the sensational discovery of a previously unknown hominin, Denisova.
Paabo was born in 1955 in Stockholm, Sweden. He defended his PhD thesis in 1986 at Uppsala University and was a postdoctoral fellow at University of Zürich, Switzerland and later at University of California, Berkeley, USA. He became Professor at the University of Munich, Germany in 1990. In 1999 he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany where he is still active. He also holds a position as adjunct Professor at Okinawa Institute of Science and Technology, Japan.
Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.
Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.
A seemingly impossible task
Early in his career, Svante Pääbo became fascinated by the possibility of utilizing modern genetic methods to study the DNA of Neanderthals. However, he soon realized the extreme technical challenges, because with time DNA becomes chemically modified and degrades into short fragments. After thousands of years, only trace amounts of DNA are left, and what remains is massively contaminated with DNA from bacteria and contemporary humans (Figure 1). As a postdoctoral student with Allan Wilson, a pioneer in the field of evolutionary biology, Pääbo started to develop methods to study DNA from Neanderthals, an endeavor that lasted several decades.
Figure 1. DNA is localized in two different compartments in the cell. Nuclear DNA harbors most of the genetic information, while the much smaller mitochondrial genome is present in thousands of copies. After death, DNA is degraded over time and ultimately only small amounts remain. It also becomes contaminated with DNA from e.g. bacteria and contemporary humans.
In 1990, Pääbo was recruited to University of Munich, where, as a newly appointed Professor, he continued his work on archaic DNA. He decided to analyze DNA from Neanderthal mitochondria – organelles in cells that contain their own DNA. The mitochondrial genome is small and contains only a fraction of the genetic information in the cell, but it is present in thousands of copies, increasing the chance of success. With his refined methods, Pääbo managed to sequence a region of mitochondrial DNA from a 40,000-year-old piece of bone. Thus, for the first time, we had access to a sequence from an extinct relative. Comparisons with contemporary humans and chimpanzees demonstrated that Neanderthals were genetically distinct.
Sequencing the Neanderthal genome
As analyses of the small mitochondrial genome gave only limited information, Pääbo now took on the enormous challenge of sequencing the Neanderthal nuclear genome. At this time, he was offered the chance to establish a Max Planck Institute in Leipzig, Germany. At the new Institute, Pääbo and his team steadily improved the methods to isolate and analyze DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA highly efficient. Pääbo also engaged several critical collaborators with expertise on population genetics and advanced sequence analyses. His efforts were successful. Pääbo accomplished the seemingly impossible and could publish the first Neanderthal genome sequence in 2010. Comparative analyses demonstrated that the most recent common ancestor of Neanderthals and Homo sapiens lived around 800,000 years ago.
Figure 2. A. Pääbo extracted DNA from bone specimens from extinct hominins. He first obtained a bone fragment from Neandertal in Germany, the site that gave name to the Neanderthals. Later, he used a finger bone from the Denisova Cave in southern Siberia, the site that gave name to Denisovans. B. Phylogenetic tree showing the evolution and relationship between Homo sapiens and the extinct hominins. The phylogenetic tree also illustrates the gene flows discovered by Pääbo.
Pääbo and his co-workers could now investigate the relationship between Neanderthals and modern-day humans from different parts of the world. Comparative analyses showed that DNA sequences from Neanderthals were more similar to sequences from contemporary humans originating from Europe or Asia than to contemporary humans originating from Africa. This means that Neanderthals and Homo sapiens interbred during their millennia of coexistence. In modern day humans with European or Asian descent, approximately 1-4% of the genome originates from the Neanderthals (Figure 2).
Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén
