Nobel Prize in Medicine for the Swede Svante Pääbo and paleogenomics

Svante Pääbo “The Neanderthals are not quite dead, they still live in us! »

He is the first to have demonstrated that the genome of today’s humans contains 1 to 3% of Neanderthal DNA. Passing through France on the occasion of the publication of his book (1), Svante Pääbo, the Swedish geneticist (2) who rewrote the history of the evolution of humanity, by putting his discipline at the service of paleontology, gives us the fruit of his research on our ancestors and our origins.

Svante Pääbo, your research shows that you are partially… a Neanderthal! How do you live it?

Svante Pääbo It’s quite nice and exciting to think that the Neanderthals are not quite dead, since they continue to live a little in us! How much of a Neanderthal am I? Like all women and men who have not recently come from sub-Saharan Africa, I have 1 to 3% of genes from Neanderthal men. Sub-Saharan Africans have almost none, as Neanderthals did not go to that part of the world.

In your book (1), you tell how, by putting your specialty, genetics, at the service of paleontology, you have developed techniques for reconstructing ancient DNA and thus been able to demonstrate that there are always 1 to 3 % Neanderthal genes in us. Is it possible to estimate the exact percentage?

Svante Pääbo It is very difficult to quantify exactly this proportion. When we have long chains of DNA, large fragments to analyze, we can be sure to map all the differences between today’s humans and these prehumans, this ancient species more than 40,000 years old. But when we only have very small fragments available, we have less genetic information. This is why we estimate at between 1 and 3% this share of Neanderthal genetics in us, modern Homo sapiens, in Europe and Asia.

Do we know what the Neanderthal genes we have inherited correspond to?

Svante Pääbo We don’t all have the same Neanderthal genes, but some are still more common in the general population. We reconstructed a really complete and good quality genome of a Neanderthal just a year and a half ago. We are therefore only just beginning to discover which genes, precisely, this group has bequeathed to us. So far we have identified that there are genes involved in the immune system, our defenses against disease. And last year we found that a fairly common Neanderthal gene is associated with the risk of type 2 diabetes, the kind that develops as you get older. It is found particularly in Asia.

We have also discovered that the genome of modern humans contains genes specific to another group of humans, contemporaries of Neanderthals, but different from them: the Denisovans. The adaptation to altitude of a majority of Tibetans is thus linked to a gene inherited from the Denisovan line: it facilitates survival on the high plateaus where there is not much oxygen. All these palaeogenetic analyzes upset our knowledge of the history of human evolution and the growth of our origins.

Who are these Denisovans, contemporaries of the Neanderthals you uncovered in 2011?

Svante Pääbo We discovered this human group by sequencing their DNA from a tiny fragment of bone: a tiny piece of a little girl’s little finger, found in the Denisova cave in Siberia. Subsequently, three teeth were discovered in the same place, but that was it. These Denisovans are closer to Neanderthals than to us: the separation of these two lineages took place only about 400,000 years ago, while our lineage separated from the common lineage of Neanderthals and Denisovans between 550,000 and 765,000 years ago.

And, as I said, some of the genetic makeup of the Denisovans has passed down to modern human populations. We find traces of it in Asia, but especially in the Pacific. This suggests that the Denisovans not only lived in Siberia, where we discovered their existence, but that they occupied a good part of the Asian continent, including all around the Pacific. We believe that it was in this region that they encountered modern humans and interbred with them. This would explain the fact that traces of their genetic baggage can be found in contemporary populations of these regions.

Let’s go back to 1995, when you started working on Neanderthal, at that time you announced that there had been no mixing between Neanderthal and modern man, Homo sapiens. Today, you say the opposite. Were you wrong?

Svante Pääbo Yes, it’s true. Contrary to the only morphological and anatomical interpretation of fossils which gives rise to all sorts of vague or contradictory interpretations, with DNA we have irrefutable proof of our mixtures. Genetics is a great strength for us, it allows us to put our theories to the test! In 1995, we were only able to map the DNA contained in small cell organelles, the mitochondria. And yet we only had a small part of it, but this mitochondrial DNA is transmitted exclusively by women. Since 2010, we have reconstituted the DNA contained in the nucleus of cells, nuclear DNA, which is transmitted by both parents. The analysis of the nuclear genome tells a much more complete and precise story than that of mitochondrial DNA: an inheritance, a transmission, even weak, towards Homo sapiens. I believe that the fact that we do not have mitochondrial DNA in common with Neanderthals is a coincidence. This DNA is transmitted exclusively by the mother. So Neanderthal women who only had boys couldn’t pass it on, and their mitochondrial DNA was completely lost. This is probably why we have not found any in our own DNA.

A few months ago, you announced that a Homo sapiens who died 40,000 years ago had a Neanderthal ancestor less than six generations earlier. So did Neanderthal and Homo sapiens mix each time they met?

Svante Pääbo How would I know? Maybe not every Saturday evening, you should probably not exaggerate! They had multiple encounters and opportunities to mingle, I’m sure. And this interbreeding is very recent, we estimate that it occurred as soon as the first modern humans left Africa: as soon as they arrived in Europe, the Middle East and Asia, mixtures took place between there 60,000 and 40,000 years old.

You have demonstrated that present-day Asians have more Neanderthal heritage than Europeans, that Africans have almost none at all, and that the inhabitants of Oceania have more Denisovan heritage than other populations of the world: does this mean that you believe that there are different human species?

Svante Pääbo You know the bad reputation of Neanderthal, who was considered a moron for a long time because of the shape of his skull… When we published our article announcing our mixture with Neanderthal, the weekly magazine Jeune Afrique published a very interesting comment which meant , in summary: “Now we understand better why Europeans are aggressive, indelicate and unsympathetic: it comes from their Neanderthal genes! The notion of species, or of “race” to use a term unfortunately overused by some, has no meaning. It is purely ideological.

But then, if there were so many mixtures…, can we consider that the Neanderthals, the Denisovans and the Homo sapiens are all of the same species?

Svante Pääbo I think that the classifications are purely academic and without interest: the discussion around what is a species, a human membership, does not make sense. We avoid talking about species and giving rise to sterile and endless debates. The term race is ridiculous, it translates either the obsession of certain dusty teachers who wish to put individuals in boxes, or of ideologues who want to exploit science. The notion of race comes from an archaic way of thinking!

Can I claim to be a “somewhat Denisovan sapiens-Neanderthal”?

Svante Pääbo If you don’t have an Asian ancestor, you are only a sapiens-Neanderthal!

Does your work explain why there are only Homo sapiens today with a little Neanderthal or Denisovan genetic background?

Svante Pääbo No, I don’t really know why these two groups disappeared, I think it’s related to the behavior of modern man. If, in the future, we can decipher the behavior potentially linked to the genes of modern humans and what drives them to act in certain ways, perhaps we will be able to better understand why they have persisted while the others disappeared. This may be a reason similar to the one causing the current extinction of orangutans: human behavior with the clearing of forests, for example…

You recently announced that you had reconstructed the DNA of 430,000 year old fossil men? How deep in time do you think it would be possible to go?

Svante Pääbo I do not think it is possible to carry out this work on remains dating back more than a million years. To have succeeded in analyzing 430,000-year-old DNA is already exceptional: there must be enough remains to analyze and the conditions for preserving the bones must be impeccable… But in any case, I very much doubt that we can go beyond a million years.

What are your future projects?

Svante Pääbo Precisely, to go back even further in time! I would like to be able to study and map the genome of the ancestors of Neanderthals as well as understand the reasons why modern humans survived while other forms of prehumans disappeared. It is an exciting project, we strive to analyze these genetic variations that have made modern man what he is.

An example, we have integrated genes into mouse cells to study their behavior. And in particular we observed changes at the level of a gene, changes that took place before the separation between Homo sapiens and Neanderthal, a specific gene that is linked to the development of language in humans. We are currently studying the learning abilities of mice following the insertion of this gene into their genetic heritage… and we have found that they manage better than their unmodified counterparts: they seem smarter! It’s all still confusing.

The Neanderthal saga rewritten.

7 to 9 million years ago: our lineage splits from that of the chimpanzee 765,000 to 550,000 years ago: our lineage splits from that of the Neanderthals.30,000 years ago: the Neanderthal lineage s extinct.1856: discovery of a Neanderthal fossil, in Germany.1995: first DNA analysis of a Neanderthal.2010: first complete DNA sequence of a Neanderthal, and proof that he bequeathed part of his genes to us .2015: Complete DNA sequence of a 430,000 year old Neanderthal ancestor.