WuXi AppTec WuXi AppTec 2022-10-03 18:04 published in Beijing
Beijing time on the afternoon of October 3, Beijing time, the highly anticipated Nobel Prize in Physiology or Medicine announced the list of winners in 2022. Svante Pääbo (Svante Pääbo) won the championship for his outstanding contributions in the field of paleogenomics. He established a brand new scientific discipline - paleogenomics. By revealing the genetic differences between all existing humans and extinct ancient humans, his discovery provides the basis for exploring “what makes us unique humans.”
▲Dr. Svante Pääbo, who won the Nobel Prize today (Picture 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 unique?
Dr. Pabo is a pioneer in this field. By sequencing the genome of the extinct Neanderthal , he gave the answer to this seemingly impossible question. In addition, he also greatly assisted in the discovery of Denisovan .
These important advances reveal a secret - there is a genetic transfer between different early races and affects all aspects of human beings today, such as immune function. These milestone breakthroughs have also brought the emergence of paleogenomics, a new scientific field, to make humans more aware of themselves.
How does human originate? Why are we different? These questions have always attracted scientists. Evidence from paleontology and archaeology shows that modern Homo sapiens originated in Africa about 300,000 years ago, while our close relatives Neanderthals lived in Europe and West Asia outside Africa about 400,000 to 30,000 years ago, and eventually went extinction. About 70,000 years ago, a group of Homo sapiens migrated from Africa to the Middle East and then went elsewhere around the world. Therefore, Homo sapiens and Neanderthals coexisted in Eurasian for tens of thousands of years. But little has been known about our relationship with the extinct Neanderthals for a long time. The key clue comes from genomic information. By the late 1990s, almost the entire human genome had been sequenced, making it possible to follow-up study of genetic relations between different populations. However, studying the relationship between modern humans and Neanderthals requires sequencing of genomic DNA collected from ancient samples.
Facing this almost impossible task, Dr. Parbo realized the technical difficulty. Over time, DNA will be chemically modified and degraded into fragments. Thousands of years later, only trace amounts of DNA remain, and the remaining DNA will be contaminated by bacteria and contemporary human DNA. Dr. Pabo began developing methods to study Neanderthal DNA, a work that lasted for decades.
▲DNA is located in two different locations in the cell: nucleus DNA contains most of the genetic information, and the remaining small part is located in mitochondrial . After ancient humans died, DNA degrades over time and is contaminated by DNA from bacteria and contemporary humans. (Image source: Reference [1])
As the analysis of small mitochondrial genomes can only provide limited information, Dr. Pabo accepted the huge challenge of sequencing Neanderthal nuclear genomes. At this time, he was given a job opportunity at the Max Planck Institute. At the new institute, Dr. Parbo and his team have steadily improved the methods for isolating and analyzing DNA from remains of ancient bones. The research team utilizes new technology to make DNA sequencing very efficient. Dr. Parbo has also hired several collaborators with expertise in population genetics and sequence analysis.
Dr. Pabo completed what seemed impossible and published his first Neanderthal genome sequence in 2010. comparative analysis showed that the recent common ancestors of Neanderthals and Homo sapiens lived about 800,000 years ago. Dr. Parbo and his colleagues can now analyze the relationship between Neanderthals and modern people from different parts of the world. Comparative analysis showed that Neanderthal DNA sequence was more similar to that of contemporary humans who originated in Europe or Asia, rather than Africa. This means that Neanderthals and Homo sapiens have been hybridized in thousands of years of coexistence . In modern humans with European or Asian descent, about 1%-4% of the genome comes from Neanderthals.
▲Dr. Pabo extracted DNA from bone samples from extinct humans. He first obtained a fragment of a bone from Neanderth, Germany, and later used bone fragments from the Denisova cave for analysis. evolution tree shows the relationship between Homo sapiens and these extinct ancient humans, and also shows the transfer between genes discovered by Dr. Parbo. (Picture source: Reference [1])
In 2008, scientists found a fragment of phalanx dating 40,000 years ago in the Denisova Cave in the south of Siberia. The bone contains very well-preserved DNA, which Dr. Parbo’s team sequenced. The results caused a sensation: This DNA sequence is unique compared to all known DNA sequences of Neanderthal and modern humans. Dr. Pabo discovered an ancient human that was unknown before, named Denisovan . Comparison of sequences with contemporaries from different parts of the world shows that gene flow has also occurred between the Denisovans and Homo sapiens. This relationship was first found in Melanesia and in other parts of Southeast Asia, where individuals carry up to 6% of Denisovan DNA. Dr. Parbo's discovery has given people a new understanding of the history of human evolution. When Homo sapiens left Africa, at least two extinct ancient human populations lived in Eurasia. Neanderthals live in the western part of Eurasia, while Denisovans live in the eastern part of the continent. During the expansion and migration of Homo sapiens outside Africa, they not only met and crossed with Neanderthals, but also with Denisovans.
Through its pioneering research, Dr. Pabo has established a brand new field of science, Paleogenomics . Following the initial discovery, his team analyzed the genome sequences of several extinct ancient humans. Dr. Parbo's discovery became a unique resource, widely used by scientists to enhance understanding of human evolution and migration. Several powerful new methods of sequence analysis indicate that ancient humans may have crossed with Homo sapiens in Africa. However, the ancient human genome that had become extinct in Africa has not been sequenced because the tropical climate accelerates the degradation of ancient DNA. Based on Dr. Parbo's discovery, we understand that the ancient gene sequences of extinct relatives also influence the physiological characteristics of humans today. An example is the EPAS1 gene of the Denisovans, which gives modern Tibetans the advantage of survival in high altitude areas. There are also several genes of Neanderthal, for example, that affect our immune response to multiple infections.
▲Dr. Pabo's discovery is of great significance. It reveals the population distribution on the earth when Homo sapiens walked out of Africa and came to all parts of the world. Neanderthals lived in the west of Eurasia, while Denisovans lived in the east. When our ancestors came to these areas, they also had mating with them, leaving eternal traces in our DNA. (Picture source: Reference [1])
Homo sapiens can create complex civilizations, carry out inventions and artistic activities, and can also operate on the entire earth's water and land range.Neanderthals also live collectively and have a big enough brain. They also use tools, but have not developed much in hundreds of thousands of years. Compared with relatives who have recently become extinct, what are the genes of Homo sapiens different from them? Through a series of groundbreaking research by Dr. Parbo, this question begins to come up with answers. Current research focuses on analyzing the functional differences caused by these genetic differences, and ultimately we will answer the ultimate question: Why are we unique humans?
Dr. Pabo's contribution allows us humans to explore their own position in the long river of history from a more original place. The winning of the Nobel Prize in Physiology or Medicine is the best compliment to its significance.
Reference:
[1] The Nobel Prize in Physiology or Medicine 2022, Retrieved October 3, 2022, from https://www.nobelprize.org/uploads/2022/10/press-medicine2022.pdf
