In early October, the scientific world is looking forward to the announcement of the Nobel Prizes. So on October 3, the Swedish committee of the Karolinska Institute surprised the world by awarding the 2022 Nobel Prize in Medicine to paleogeneticist Svante Paabo. Svante Paabo devoted himself throughout his scientific career to studying the DNA of hominins that lived in the past and disappeared. His research has shed light on the evolutionary history of hominins and their relationship to modern Homo sapiens.
The human genome, among other things, is an important historical book, since it accumulates genetic diversity coming from the depths of the centuries of its evolutionary course. Thus, by reading and comparing the genomes of different species, it is possible to reconstruct the historical course and relationships of these species to each other. As an example, I will mention that of the species living on our earth today, the chimpanzee genome is the closest (similar) to our own genome; the frequency of mutations in DNA over time allows us to calculate that our common ancestor lived about 6-7 million years ago.

Before Svante Paabo’s years of work, we knew little about other extinct species that are much more closely related to us than chimpanzees. In 1856, bones were found in a cave in the Neander Valley in Germany that were thought to belong to a hominid, naturally called the Neanderthal hominid. But what was the history of this humanoid and what is its relation to us? Svante Paabo, for his many years of scientific research, managed to read the Neanderthal genome and shed light on this stage of his life on earth. The plot is very complex. DNA isolated from bones about 40,000 years old fragments into small fragments, undergoes chemical changes over time, mixes with DNA from bacteria and other species, mainly modern human DNA from those who work with bones. Svante and his colleagues spent several years developing and refining methods to read archaic DNA, and they were able to read small fragments of the Neanderthal genome. Gradually, with the development of technology, the complete identification and reading of the Neanderthal genome was achieved! So we learned that this species lived from about 400,000 to 30,000 years before the present, mainly in Eurasia. Our species, when it emerged from Africa about 80,000 years ago, encountered the Neanderthals about 40,000 years ago and probably wiped them out because it was more capable of evolution than they were. As expected, our species mixed genetically with Neanderthals and produced children who were hybrids of Homo Sapiens and Homo Neanderthal. How can we know? Because Europeans basically have about 1-4% of the remnants of the Neanderthal genome in our genome. A human specimen has also been found that lived 40,000 years ago, whose ancestor four to six generations ago was a Neanderthal.

Archaeal diversity in regions on chromosomes 3 and 12 has recently been found to be associated with respiratory failure in COVID-19.

In 2008, a hominid little finger bone was found in Denisova Cave in Altai, Siberia. The genome of this specimen showed that it belonged to another Neanderthal hominid named Svante Paabo Denishova (Homo Denishova). Also, with great luck, a specimen was found that was a child from a mixture of Neanderthal and Denisovan! As in the story of the Neanderthals, our species also intermixed genetically and had children with Denisovans. As a result, some modern human populations, such as the Melanesians, have Denisova remnants in 4-6% of their genome.

Recall that over the past million years, other species of hominids lived on Earth, which are now extinct. Two of them, Neanderthal hominids and Denisovan hominids, met with modern humans 40-60 thousand years ago and genetically mixed, i.e. had children with each other. It is highly likely that there are other unknown hominids that have yet to be discovered. In today’s human genome, there are remnants of mixing with these other hominids.

You ask me why the Nobel Prize in Medicine was given for discoveries that are, of course, important for the historical course of species, but at first glance are not so important for the diagnosis and treatment of countless diseases of modern man?

The answer is complex. The secret of many diseases lies in the diversity of our DNA. Our current knowledge of the medical significance of this diversity is very limited, covering only approximately 0.37% of the genome. Comparing the genomes of different species with our own genome allows us to figure out what is important and functional in our genome and how it is associated with various diseases. Comparison with the Neanderthal and Denisovan genomes allows us to understand our evolutionary advantage in brain development and mental function. It also opens up opportunities for us to understand adaptation and survival in a changing environment in different parts of the earth. A prime example is the EPAS1 gene variants that provide adaptation to high altitudes, such as in the Tibetan population. These EPAS1 gene variants are descended from Denisovans who lived in this wider area. Other variants around the TLR6, STAT2, or OAS genes are of Neanderthal or Denisovan diversity and are important for microbial recognition, allergic disease, and defense against viruses. Archaic diversity in regions on chromosomes 3 and 12 has recently been found to be associated with the onset of respiratory failure from Covid19. Serious research is currently underway to find regions of the Neanderthal or Denisovan genome that are related to human diseases. In the next few years, we will learn a lot more about human physiology and biological function by comparing our genomes with those of other hominids who shared the earth with us tens or hundreds of thousands of years ago. Their presence was important to us. And their remains are valuable for history, identity and our health.

Dear Svante Paabo and our dear unknown humanoid cousins, thank you very much!

* Mr. Stylianos Antonarakis is Professor Emeritus of Genetic Medicine at the University of Geneva, Member of the Swiss Academy of Sciences and former President of the International Human Genome Organization (HUGO).