▎WuXi AppTec Content Team Editor
On the afternoon of October 3rd, Beijing time, the highly anticipated Nobel Prize in Physiology or Medicine announced the 2022 winners, Svante Pabo Dr. Pääbo was awarded the laurel for his outstanding contributions to the field of paleogenomics. He established a whole new scientific discipline – paleogenomics. By uncovering the genetic differences between all living humans and extinct hominins, his findings provide a basis for exploring “what makes us uniquely human.”
▲Dr. Svante Pääbo, who won the Nobel Prize today (Image source: Reference [1])
Curiosity is human nature. While looking up at the stars, we also think about our own destiny: Who are we? Where did it come from? Where are you going? What makes us human and what makes us so different?
Dr. Pabo was a pioneer in this field. By sequencing the genome of extinct Neanderthals, he has answered this seemingly impossible question. In addition, he greatly assisted in the discovery of the Denisovans.
These important advances have revealed a secret – the transfer of genes between different early human species that affects many aspects of human beings today, such as immune function. These milestone breakthroughs have also led to the emergence of a new scientific field of paleogenomics, allowing humans to understand themselves better.
How did humans originate? Why are we different? These questions have always fascinated scientists. Evidence from paleontology and archaeology suggests that modern Homo sapiens originated in Africa about 300,000 years ago, while our closest relatives, the Neanderthals, lived in Europe and West Asia outside of Africa about 400,000 to 30,000 years ago , eventually leading to extinction. About 70,000 years ago, a group of Homo sapiens migrated from Africa to the Middle East and then to the rest of the globe. Thus, Homo sapiens and Neanderthals coexisted in Eurasia for tens of thousands of years. But little has been known for a long time about our relationship with the extinct Neanderthals. And the key clues come from genomic information. By the late 1990s, nearly the entire human genome had been sequenced, making it possible to follow up on genetic relationships between different populations. However, studying the relationship between modern humans and Neanderthals requires sequencing genomic DNA collected from ancient samples.
Faced with this nearly impossible task, Dr. Pabo realized the technical difficulties. Over time, DNA is chemically modified and degraded into fragments. Thousands of years later, only trace amounts of DNA are left, and what remains can be contaminated with DNA from bacteria and contemporary humans. Dr. Pabo began developing methods to study Neanderthal DNA, a work that continued for decades.
▲DNA is located in two different locations within the cell: DNA in the nucleus contains most of the genetic information, and the rest is located in the mitochondria. After the death of ancient humans, DNA degrades over time and can also be contaminated with DNA from bacteria and contemporary humans. (Image source: Reference [1])
Since the analysis of the small mitochondrial genome can only provide limited information, Dr. Pabo took on the enormous challenge of sequencing the Neanderthal nuclear genome. At this time, he got a job offer at the Max Planck Institute. At the new institute, Dr. Pabo and his team have steadily improved their methods of isolating and analyzing DNA from ancient bone remains. The research team used new technology to make DNA sequencing very efficient. Dr. Pabo has also hired several collaborators with expertise in population genetics and sequence analysis.
Dr. Pabo accomplished the seemingly impossible and published the first Neanderthal genome sequence in 2010. Comparative analysis shows that the most recent common ancestor of Neanderthals and Homo sapiens lived about 800,000 years ago. Dr. Pabo and his colleagues can now analyze the relationship between Neanderthals and modern humans from different parts of the world. Comparative analysis showed that the DNA sequence of Neanderthals was more similar to that of contemporary humans originating in Europe or Asia than in Africa. This means that Neanderthals and Homo sapiens interbred over thousands of years of coexistence. In modern humans of European or Asian ancestry, approximately 1%-4% of the genome is from Neanderthals.
▲Dr. Pabo extracted DNA from bone samples of extinct humans. He first obtained a fragment of a bone from Neanderthals in Germany, and later also used bone fragments from Denisovan caves for analysis. The evolutionary tree shows the relationship between Homo sapiens and these extinct hominins, as well as the transfer between genes discovered by Dr. Pabo. (Image source: Reference [1])
In 2008, scientists discovered a 40,000-year-old finger bone fragment in the Denisova cave in southern Siberia. The bone contained remarkably well-preserved DNA, which Dr. Pabo’s team sequenced. The results were sensational: This DNA sequence was unique compared to all known Neanderthal and modern human DNA sequences. Dr. Pabo discovered a previously unknown hominin named Denisovans. Sequence comparisons with contemporaneous humans from different parts of the world suggest that gene flow also occurred between Denisovans and Homo sapiens. This relationship was first found in Melanesia and other parts of Southeast Asia, where individuals carry up to 6% of Denisovan DNA. Dr. Pabo’s findings shed new light on human evolutionary history. When Homo sapiens left Africa, at least There are two extinct hominin populations that inhabited Eurasia. Neanderthals inhabited western Eurasia and Denisovans inhabited the eastern part of the continent.The expansion of Homo sapiens outside Africa And during their eastward migration, they met and interbred not only with Neanderthals, but also with Denisovans.
Through his groundbreaking research, Dr. Pabo established a new field of science, paleogenomics. Following the original discovery, his team analyzed the genome sequences of several extinct hominins. Dr. Pabo’s findings have become a unique resource, widely used by scientists to advance understanding of human evolution and migration. Several powerful new methods of sequence analysis point to the possibility that hominids interbred with Homo sapiens in Africa. However, the genomes of ancient humans that went extinct in Africa have not been sequenced because tropical climates accelerate the degradation of ancient DNA. Based on Dr. Pabo’s findings, we understand that the ancient genetic sequences of those extinct relatives also influenced the physiology of present-day humans. An example is the Denisovan EPAS1 gene, which gave modern Tibetans an advantage in high altitudes. There are, for example, several Neanderthal genes that influence our immune response to a variety of infections.
▲Dr. Pabo’s findings are significant, revealing the distribution of human populations on Earth as Homo sapiens moved out of Africa and around the globe. Neanderthals lived in western Eurasia, while Denisovans lived in the east. When our ancestors came to these regions, they also mated with them, leaving a permanent trace in our DNA. (Image source: Reference [1])
Homo sapiens was capable of creating complex civilizations, inventing and artistic activities, and operating on land and water all over the planet. Neanderthals also lived in groups and had large enough brains. They also use tools, but haven’t developed much in hundreds of thousands of years. How are Homo sapiens genetically different from their closest but extinct relatives? Through a series of pioneering studies by Dr. Pabo, this question is beginning to be answered. Current research focuses on analyzing the functional differences brought about by these genetic differences, and ultimately we will answer the ultimate question: why are we uniquely human.
Dr. Pabo’s contributions allow us humans to understand our place in history from a more original place. To win the Nobel Prize in Physiology or Medicine this time is the best tribute to its significance.
References:
[1] The Nobel Prize in Physiology or Medicine 2022, Retrieved October 3, 2022, from https:https://www.nobelprize.org/uploads/2022/10/press-medicine2022 .pdf
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