Shulou(Shulou.com)11/24 Report--

At about 17: 30 Beijing time on October 3, 2022, Swedish geneticist Svante P á bo won the 2022 Nobel Prize in Physiology or Medicine for his contribution to the extinct ancient human genome and human evolution.

Svante P ä bo was born in Stockholm, Sweden in 1955. He defended his doctoral thesis at Uppsala University in Sweden in 1986 and did postdoctoral research at the University of Zurich in Switzerland and the University of California at Berkeley in the United States. He was a professor at the University of Munich in Germany in 1990. In 1999, he founded the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany, and is still active today. He also serves as an adjunct professor at the University of Science and Technology in Okinawa, Japan.

Human beings have always been fascinated by their origins. Where do we come from and what do we have to do with previous creatures on earth? What makes us-- Homo Sapiens-- different from other ancient humans?

Through his groundbreaking research, Swanter Pabo has done what seems impossible: sequencing the genome of Neanderthals, an extinct relative of mankind. Another of his shocking achievements was the discovery of a previously unknown ancient human: the Denisovans. Pabo also found that gene transfer (gene transfer) had taken place from these now extinct hominids to Homo sapiens after migrating from Africa about 70,000 years ago. This ancient gene flow still has physiological implications for humans today, such as affecting the response of our immune system to infection.

Pabo's groundbreaking research gave birth to a new discipline-paleogenomics (paleogenomics). By revealing the genetic differences between modern and extinct humans, his findings laid the foundation for human beings to explore their own uniqueness.

Where do we come from? Since ancient times, humans have been interested in their own origins and what makes us different. Paleontology and archaeology are very important to the study of human evolution. Research evidence suggests that Homo sapiens, a modern anatomical human, first appeared in Africa about 300,000 years ago, while Neanderthals, our closest relatives, developed outside Africa and lived in Europe and West Asia between 400,000 and 30,000 years ago and then became extinct.

About 70,000 years ago, Homo sapiens migrated from Africa to the Middle East and from there spread to other parts of the world. As a result, Homo sapiens and Neanderthals coexisted in most of Eurasia for tens of thousands of years. But how much do we know about our relationship with the extinct Neanderthals? Genomic information may provide clues. By the late 1990s, almost the entire human genome had been sequenced. This is a great achievement that makes it possible to study the genetic relationship between different populations. However, to study the relationship between today's humans and extinct Neanderthals, it is necessary to sequence the genomic DNA found in ancient specimens.

The seemingly impossible task early in his career, Swanter Papo was fascinated by the possibility of using modern genetic methods to study Neanderthal DNA. However, he soon realized the extreme technical challenges. Because over time, DNA will be chemically modified and degraded into short fragments. Thousands of years later, only a small amount of DNA was left, and the rest was heavily contaminated with bacteria and contemporary human DNA (figure 1). As a postdoctoral fellow of Alan Allan Wilson, a pioneer in evolutionary biology, Papo began to develop a method for studying Neanderthal DNA, which has been going on for decades.

Figure 1. DNA is located in two different compartments in the cell. The nuclear DNA in the nucleus contains most of the genetic information, while the smaller mitochondrial genome, which exists in the mitochondria, has thousands of copies. When the organism dies, DNA will degrade over time, leaving only a small amount of residue. At the same time, it can also be contaminated by DNA from bacteria and modern humans. In 1990, Papo was hired as a professor at the University of Munich to continue to study ancient DNA. He decided to analyze DNA from Neanderthal mitochondria, organelles that contain DNA in cells. The mitochondrial genome is small, containing only a small portion of the genetic information in cells, but there are thousands of copies in each cell, increasing the chances of success. Using his improved method, Pabo managed to sequence a mitochondrial DNA from a 40,000-year-old bone, allowing us to obtain the DNA sequence of an extinct human relative for the first time. Compared with the DNA of contemporary humans and chimpanzees, Neanderthals are genetically different.

Sequencing the genome of Neanderthals due to the limited information brought by the analysis of the genome in the mitochondria, Papo took on the great challenge of sequencing the nuclear genome of Neanderthals. At that time, he was given the opportunity to create the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany. In this new institute, Pabo and his team are constantly improving the method of isolating and analyzing DNA from the remains of ancient humans. With the help of emerging technologies, they have significantly improved the efficiency of DNA sequencing. Pabo has also hired several important collaborators who specialize in population genetics and advanced sequence analysis. His efforts were successful. Papo accomplished the seemingly impossible task and released the first Neanderthal genome sequence in 2010. Comparative analysis shows that the most recent common ancestor of Neanderthals and Homo sapiens lived about 800000 years ago.

Figure 2. A. Papo extracted DNA from the bones of extinct ancient humans. He first obtained a fragment of a Neanderthal bone found in Germany. The name of the Neanderthal comes from the excavation site. Later, he studied a finger bone from the Denisova cave in southern Siberia, whose name comes from the name of the excavation site. b. The phylogenetic tree shows the evolution and relationship between Homo sapiens and extinct ancient humans, as well as the gene flow discovered by Pabo. Pabo and his colleagues can now analyze the relationship between Neanderthals and modern humans from all over the world. Comparative analysis shows that the DNA of modern humans in Europe or Asia is more similar to that of Neanderthals than that of modern humans living in Africa. This means that Neanderthals and Homo sapiens interbred with each other during thousands of years of coexistence. About 1% of the genome of modern humans of European or Asian descent comes from Neanderthals (figure 2).

An exciting discovery: in 2008, scientists found a 40,000-year-old fragment of the phalangeal bone in the Denisova cave in southern Siberia. The bone contained an unusually well-preserved DNA, which was sequenced by a team led by Pabo. They found that this DNA sequence is unique compared to all known sequences from Neanderthals and today's humans. Pabo discovered a previously unknown ancient human and named it Denisova. Comparative analysis shows that compared with contemporary human sequences from different parts of the world, gene flow also occurs between Denisovans and Homo sapiens. The relationship first appeared in people in Melanesia and other parts of south-east Asia, where people carry 6 per cent of Denisovan DNA.

Pabo's discovery gives us a new understanding of the history of human evolution. At least two then-extinct hominid populations lived in Eurasia when Homo sapiens moved out of Africa. Neanderthals once lived in western Eurasia, while Denisovans lived in the east. During the outward expansion and eastward migration of Homo sapiens, they not only met and crossed with Neanderthals, but also crossed with Denisovans. (figure 3)

Paleogenomics and its correlation as a result of these groundbreaking studies, Swanter Papo established a new scientific discipline-paleogenomics. After the initial discovery, his team has completed the analysis of several other genome sequences from extinct humans. Pabo's discovery provides a unique resource that can be widely used by the scientific community to better understand human evolution and migration. These powerful new methods for DNA sequence analysis suggest that ancient humans may also have fused genes with Homo sapiens in Africa. However, due to the accelerated degradation of ancient DNA in tropical climates, the genomes of extinct ancient humans in Africa have not been sequenced.

As a result of Swanter Pabo's discovery, we are able to understand that ancient gene sequences from our extinct relatives have affected the physiology of humans today. A specific example is the Denisovan EPAS1 gene that exists in humans today, which gives individuals the advantage of living at high altitudes and is common among people living in Xizang today. Another example is that Neanderthal genes affect the way we respond to different types of infections.

Figure 3. Pabo's findings provide important information about the state of the world's population as Homo sapiens moved out of Africa and moved into other places. Neanderthals once lived in western Eurasia, while Denisovans lived in the east. Hybridization occurs when Homo sapiens spread all over the continent, and these traces remain in our DNA. What makes us unique human beings? Creating complex cultures, advanced inventions and image art is a unique ability of Homo sapiens, and they can migrate across open waters to all parts of our planet (figure 4). Neanderthals live in groups and have larger brains (figure 4). They also use tools, but these tools have not been improved for hundreds of thousands of years. Pabo's groundbreaking work identified the genetic differences between Homo sapiens and our closest extinct relatives, and we knew the difference between them. Intensive ongoing research focuses on analyzing the functional impact of these differences, with the ultimate goal of explaining what makes us unique human beings.

Figure 4. Pabo's groundbreaking work lays the foundation for explaining what makes us unique human beings. Official website of the Nobel Prize: https://www.nobelprize.org/

This article is from the official account of Wechat: global Science (ID:huanqiukexue), author: global Science

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