2022-10-06| Special

Svante Pääbo Wins Physiology or Medicine Nobel Prize for Human Evolution Discoveries

by Reed Slater
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On October 3, the Nobel Assembly at Karolinska Institutet awarded Svante Pääbo the 2022 Nobel Prize in Physiology or Medicine for his work and discoveries regarding the genomes of ancient hominins and human evolution. By uncovering valuable genomic data from Neanderthals and another ancient hominin species he helped discover, Denisovans, Pääbo provided precious new insights into human evolution which spurred a continuing revolution to understand what makes humans unique. 

The Nobel Assembly at Karolinska Institutet awarded Svante Pääbo the 2022 Nobel Prize in Physiology or Medicine for his work and discoveries regarding the genomes of ancient hominins and human evolution.

Pääbo’s Early Work Leading to his Seminal Discoveries

Long interested in ancient history, Pääbo spent his early academic career studying Egyptology, researching adenoviruses and their interaction with the immune system. Creative and ambitious, he started a secret side project trying to isolate DNA from mummy specimens. He would later admit that his early work was rudimentary and flawed, but it set the stage for the rest of his career dedicated to ancient DNA collection and examination.

DNA is localized in two different compartments in the cell. (Source: The Nobel Prize)

Quickly, Pääbo learned the many limitations of collecting and evaluating ancient DNA. Some of the most challenging aspects to overcome in the process were specimen decay and contamination. Researchers discovered that colder climates provided better conditions for specimen preservation than warmer geographic regions. So, despite the interest in Africa because of its suspected role in human evolution and migration, Pääbo shifted his focus to higher latitudes in search of better-preserved specimens.

Pääbo first turned to the Neandertal Valley in Germany, where the first Neanderthal remains were discovered in 1856. He eventually got his hands on some Neanderthal bones, which he hoped to examine and isolate DNA from to compare to modern humans. With the help of newly-invented polymerase chain reaction (PCR) analysis, Pääbo examined the specimen’s mitochondrial DNA (mtDNA). The initial comparisons showed that Neanderthals likely went extinct without contributing mtDNA to present-day humans. Still, Pääbo did not stop there because he knew the limitations of mtDNA compared to nuclear DNA.

Pääbo extracted DNA from bone specimens from extinct hominins. (Source: The Nobel Prize)

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The Quest to Complete the Neanderthal Genome

Despite the many discoveries mtDNA analysis led to, Pääbo knew that he needed to obtain and examine more nuclear DNA to better understand ancient hominin’s relationship to modern humans. Some limitations associated with mtDNA are that it is only passed down through the mother and it is much smaller than nuclear DNA. At only 16,500 base pairs, mtDNA is substantially smaller and less informative than the three billion base pairs found in nuclear DNA. 

After analyzing hundreds of Neanderthal samples and refining research and examination processes, Pääbo published a draft of a Neanderthal nuclear genome sequence. Though he was a driving force, the project took the help of experts from various fields around the world to help improve sequencing processes and establish better protocols for specimen examination. 

With the Neanderthal nuclear genome draft in hand, Pääbo and other researchers made several discoveries and obtained more evidence for existing theories. One of the most substantial discoveries was that the average divergence of Neanderthal and present-day human nuclear DNA was about 825,000 years ago, making it much earlier than many previously thought. 

Discovering Denisovans

In tandem with the Neanderthal nuclear genome draft, Pääbo had a hand in discovering a previously unknown ancient hominin species based on DNA from a finger found in the Altai mountains in southern Siberia. Located in the Denisova cave, the new species was coined Denisovan and provided even more insights into the complexities of hominin evolution. 

Pääbo’s discoveries have provided important information on how the world was populated at the time when Homo sapiens migrated out of Africa and spread to the rest of the world. (Source: The Nobel Prize)

After finding more Denisovan specimens, Pääbo continued his work in ancient DNA analysis to uncover the mysterious species’ role in hominin evolution. Pääbo discovered that Neanderthals and Denisovans likely mixed during their shared time on the planet and that both species likely interacted with ancient Homo sapiens. He even found that Denisovans and ancestors of Melanesians mixed, but because of the spread of Homo sapiens, the interbreeding did not affect non-African populations. 

His work on ancient DNA analysis uncovered a wealth of new information on ancient hominin species and their geographic dispersion, timelines, and links to Homo sapiens. The field continues to grow rapidly thanks to Pääbo’s contributions which led to the new discipline of Paleogenomics.

Pääbo’s discoveries and contributions to the field are nothing short of breathtaking themselves, but just as exciting are the research development programs it continues to inspire to understand better where humans come from and why we have thrived the way we have. Through dedication and sheer passion, Pääbo’s Nobel Prize is well-deserved, and the foundation he laid will serve researchers for generations to come. 

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