2022 Nobel Prize in Physiology or Medicine

    From - The Noble Prize 2022,

   Edited by Amal Udawatta,

Svante Pääbo – awarded the 2022 Nobel Prize in Physiology or Medicine – became fascinated by the possibility of utilising modern genetic methods to study the DNA of Neanderthals. However, he soon realised the extreme technical challenges, because with time DNA becomes chemically modified and degrades into short fragments. 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 endeavour that lasted several decades.

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 analyse 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.

In 2008, a 40,000-year-old fragment from a finger bone was discovered in the Denisova cave in the southern part of Siberia. The bone contained exceptionally well-preserved DNA, which this year’s medicine laureate Svante Pääbo and his team sequenced. The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans.

Pääbo had discovered a previously unknown hominin, which was given the name Denisova. Comparisons with sequences from contemporary humans from different parts of the world showed that gene flow had also occurred between Denisova and Homo sapiens. This relationship was first seen in populations in Melanesia and other parts of South East Asia, where individuals carry up to 6% Denisova DNA. These discoveries have generated new understanding of our evolutionary history.

Svante Pääbo took on the enormous challenge of sequencing the Neanderthal nuclear genome. At Max Planck Institute in Leipzig, Germany, Pääbo and his team steadily improved the methods to isolate and analyse DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA highly efficient.

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.

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.

The 2022 Nobel Prize in Physiology or Medicine has been awarded to Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution.”

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