Dangerous connections, or a Novel in the genes
Cro-Magnons, Neanderthals and Denisovans
Mikhail Gelfand, <url>In the joint project "Skoltech Lecture Hall in Polit.
ru" – Mikhail Gelfand, Doctor of Biological Sciences, Professor, Member of the European Academy, Vice-President of Skoltech for Biomedical Research and Head of the laboratory at the Harkevich Institute of Information Transmission Problems of the Russian Academy of Sciences.
Several tens of thousands of years ago , three different groups of people lived on the territory of Eurasia: Cro-Magnons, Neanderthals and Denisovans. Cro–Magnons are our ancestors who came out of Africa 70 thousand years ago. Neanderthals are also our ancestors, as are Denisovans. All of them "met" with each other, started families and, of course, gave birth to children. These "Les Liaisons dangereuses" (dangerous connections) are recorded in our genomes and the genomes of ancient people, which scientists have managed to read.
Professor Mikhail Gelfand tells his version of the famous novel, and you and I will try to understand the dangerous ties of our distant relatives and find answers to exciting questions: who are the people who stood at the origins of the reasonable man? What happened to them in the process of biological evolution? And what do they have to do with us living in the XXI century?
Gelfand:Good afternoon! I will talk about who, to some extent, where, obviously with whom I was engaged... Well, and what – you'll guess for yourself.
Some ancient ideas about how this happened are drawn on this poster of some old and apparently rather stupid Hollywood movie. Students gave it to me at one time especially for lectures , and I now insert it everywhere.
Poster of the film "Neanderthal", USA, 1953.A more scientific, but also not quite correct representation is this wonderful picture, which is already seventy years old.
But I still remember my children's popular science books, which were arranged in the same way: first there were some monkeys, then some ape-men, then Australopithecines, then Neanderthals, and then we grew out of Neanderthals. Neanderthals , according to such classical ideas of people who were engaged in anthropogenesis, were the ancestors of Cro-Magnons.
That's not true! Because for quite a long time, although already in my memory, it turned out, again – according to anthropological data, without any genomes, that Neanderthals are not our ancestors, and Cro–Magnons are actually us. Neanderthals are a sister branch to Cro-Magnons, they separated from the branch that goes to us, about half a million years ago in Apparently, they wandered along the Mediterranean coast through what later became Turkey to Eurasia and lived happily ever after here. And then the next wave of migration happened, and Cro-Magnons came to Europe, where both existed for a while, and then the Neanderthals slowly disappeared. This is classical anthropology. It was clear that in Eurasia two branches of people lived at the same time.
The question is whether they coincided not only in time, but also in space. That is, the question is whether they interacted with each other and if so, how. There were many different archaeological battles on this occasion. It seems that there were caves in which Neanderthal and Cro-Magnon layers interspersed, and this means that if they did not see each other personally, then, in any case, they lived in the same place and at about the same time. And other archaeologists said that there was bad stratigraphy in these caves, because foxes or other animals had dug everything up.
Another interesting question is how close this face-to -face communication was. There were some bones, skeletons or skulls that seemed to have mixed signs of both. In the classical picture, this would be interpreted as intermediate skulls, but we now know that since Neanderthals are not the ancestors of Cro-Magnons, intermediate skulls cannot arise by direct inheritance, so this is the result of some kind of hybridization. So, we not only saw each other, but also communicated intensively. Well, other people said, "No, you're making it up, in fact, you can't read anything like that in these turtles ."
And then, as often happens, molecular biologists came, and the battles more or less stopped. I, in fact, will tell a story about how some battles stopped and other battles began. It began in 1997, quite a long time ago, when a fragment of the Neanderthal DNA sequence was determined, the very first. There was a small fragment of the genome, mitochondria. While it is not necessary to understand what mitochondria is, when it is necessary, I will tell you. There is a book by Svante Paabo "Neanderthal. In search of the Vanished genome" is the story of his love for ancient DNA, and how he materialized this love in experimental methods – a rather interesting scientific autobiography.
Nine years have passed, and fragments with a total length of one million nucleotides, about three hundredths of a percent of the entire genome, have been identified. Two articles were published simultaneously, made by different methods, but it was a false start, a significant part of the important conclusions turned out because some laboratory assistant inadvertently sneezed into a test tube. In particular, they saw the Y chromosome, and then it turned out that this Neanderthal was a girl and she could not have any Y chromosome. And this means that it was a laboratory assistant, not a laboratory assistant, because, as we know, only men have Y chromosomes. In general, it doesn't really count, but it became clear that the future is already knocking on the door. The Paabo group spent several more years to improve the methods and figure out how to avoid contamination. Finally, ten years ago – this year we can even celebrate the anniversary – the first draft, rather rudely read, but, in general, a fairly complete genome of a Neanderthal was published. It happened on May 7, 2010. Interestingly, there are two Russian archaeologists among the authors of this article.
DNA was isolated from several bones. The main Neanderthal was from the Vindija cave in Croatia. And, besides, there were also materials of the worst preservation – that is, bones of the same preservation, but the molecular material itself was there of the worst preservation, fragments were, in short– from El Sidron (Cueva de El Sidrón) in Spain, actually from the valley of the Neander River, after which the Neanderthals were named, and from the Mezmayskaya cave in the North Caucasus, in Adygea. This is Russia's contribution to this science. If someone needs a reason for national pride, then, for example, you can be proud that our Neanderthal is the oldest.
The most interesting thing in this article was written: somewhere from 1 to 4% of the genome of each of us (assuming that there are no pure Africans among the listeners) is of Neanderthal origin. This is a direct proof that they not only saw each other, but also communicated quite closely, such an effect could only occur as a result of direct hybridization.
How was it shown? Look: each red triangle and blue square corresponds to a fragment of the genome of about a million base pairs. And these are the genomes of two specific, not average people. That is, there should be six thousand such points. A European is blue squares, an African is red triangles. On the horizontal axis – the number of differences per fragment with a Neanderthal. And on the vertical axis – the number of differences in this fragment between this anonymous European or African and one very specific European, whose name is Craig Venter, is the first person whose genome has been fully identified and published.
Since different parts of the genome change at different rates, then, accordingly, some points have a lot of differences (these are fragments that change quickly), some have little, and with both Neanderthal and Craig Venter; and all these points form, as they should, such an elongated cloud.
But there is a paradoxical square in which there are almost only European fragments. There are few differences in these fragments between our anonymous European and a Neanderthal, but there are many differences between this European and another European, Craig Venter.
These cannot be areas that evolve slowly, because then there would be little difference with Craig Venter, too. These cannot be areas that evolve quickly, because then there would also be a lot of differences with a Neanderthal. These are the areas that our anonymous European has of Neanderthal origin. And this is direct proof.
Then you can simply calculate the proportion of these fragments in the genome, and it turns out that it is somewhere 2%, the initial estimate was from 1 to 4%, so on average each of us has such fragments. My Neanderthal fragments are defined as follows: these are fragments of my genome where I am no different from a Neanderthal and very different from most of you. Here in these places I am a Neanderthal. And this was the final, arithmetic proof.
Shortly before 2010, the hunt for Neanderthal bones began. Suddenly, archaeologists turned out to be the "kings of the mountain", they had a unique resource on which to do amazing science. In this hunt, we reached the Denisova Cave in the Altai. A nice cave, very cozy, a shallow clean river flows below, there is a forest around. There are natural chimneys in the cave, that is, you can make a fire there. And it also turned out to have unique properties, no one knows why: in those physico-chemical conditions that exist in it , DNA is very well preserved.
And so Svante Paabo and his comrades reached the Novosibirsk archaeologists who had been excavating this cave for many years, bargained with them about the bones and decided: "Cool, we're going to have a lot of Neanderthals now. We have European Neanderthals from Croatia, Spain and Adygea, and now we will have Asian Neanderthals." Anthropologists have long known that there were Neanderthals in Altai.
But an amazing thing was revealed, which was connected with a small bone, the phalanx of the little finger. And there was enough DNA in it to identify a genome with good coverage, in good quality – it turned out to be no Neanderthal. It turned out to be a completely separate person, a separate branch, also parallel to the Neanderthals and us. They were named Denisovans in honor of the cave.
That is, the picture of the spring of 2010 was arranged as follows: there were primitive people, a branch of Homo erectus departs from them, from which Neanderthals wander from Africa to Eurasia. After that, the divergence begins, the branching of branches going to modern people, Cro-Magnons. The South African Khoisan peoples were the very first to separate, and after that they lived in isolation for quite a long time. Then all sorts of diversity accumulates in Africa, and one branch goes to Eurasia and then splits into Papuans, East Asians, Europeans.
And the picture of autumn 2010 is different, a new branch appears, Denisovtsy. They are a little bit closer to the Neanderthals than to us. That is, they are still a sister branch to the Neanderthals, but they separated a long time ago. In this sense, they can be considered completely independent. Then there was the hybridization of Neanderthals with the common ancestors of Euroasians, as well as the hybridization of Denisovans with the ancestors of Papuans. That is, you and I, in the first approximation, do not have Denisov DNA. But the Papuans have about 5% of the Denisovans. That is, the Papuan has 2-2.5% Neanderthal DNA and about 5% of the Denisovan.
We know Denisovans from one cave, from a small set of small bones. There are no complete skeletons in this cave, we still don't have a single large Denisovan bone, only these small bone fragments. A tooth – you can understand how you ended up in a cave: someone knocked out a tooth, it's lying there. How the phalanx of the little finger turned out to be a little more difficult, but, apparently, there was also some small self–mutilation. But there are no real skeletons, burials of Denisovites, no skulls, no large bones, nothing. That is, almost everything we know about them , we know from the genome. And only from one cave in Altai (I will recover a little later ). But imagine the settlement of Indonesia and Australia with a visit to Altai is a very interesting geography. That is, it is clear that in fact the distribution area of Denisovans was much larger. It's just that the bones haven't been preserved.
That is, not only do we now know that our ancestors hybridized with Neanderthals, but we also know that the ancestors of the Papuans found Denisovans somewhere and hybridized with them too.
In 2014, they took another bone from Denisova Cave. It is already bigger, it is the phalanx of the big toe, already as much as 2 cm. They said, "Oh, cool, now we're going to have another Denisovan." Bang! It turned out to be a Neanderthal. That is, both Denisovans and Neanderthals lived in the same Denisova cave , there are bones of both.
Then they took the teeth, extracted DNA from the teeth, found more Denisovans, determined that Denisovans lived in this cave for about 60 thousand years, that is, for a very long time. (Well, not that they lived there all the time – we don't know that.) The oldest Denisov bones are 110 thousand years ago, the young Denisov teeth are 50 thousand years ago. That is, the population of Denisovans was stable. That means she wasn't small. A group of thirty people 60 thousand years will not last in the same place. It turns out as if there is such a big picture, and we wiped a small, small fragment and look at it, and everything else is still somehow smeared and not visible. That is , there really were, apparently, a lot of Denisovites.
Now: what can we do with this, with this joy? We can take our genomes with you, many, many genomes of modern people. Each of them has about 2% of Neanderthal fragments. These fragments are different for different people. Therefore, if we identify these fragments in different people, and then combine them all, then we will reconstruct the genome of the Neanderthal who, in fact, hybridized with our ancestors. You can do this separately for Asians, separately for Europeans.
What is useful to understand here? Two things: first, it's good if this Neanderthal was one particular one. In fact, most likely, this is not the case, which means that we are reconstructing some chimera. Because one person has Neanderthal fragments from one Neanderthal ancestor, another from another, and we reconstruct them into something in between. And this, in principle, is not insanely scary, we are used to working with it, because the very first human genome is also a chimera, it is combined from the sequences of several people. But it's just useful to keep in mind. And the second is more interesting – we see that these fragments lie densely somewhere, and there are very few Neanderthal fragments somewhere. This is what is called "Neanderthal deserts", these are all large fragments of chromosomes, many millions of pairs of nucleotides. There are such "Neanderthal deserts" where there are practically no Neanderthal fragments. And you will remember this for now, and then I will make a great science out of the analysis of these fragments.
Then we made another comparison, not just for Europeans and Asians, but for representatives of different populations. And it can be seen that the Neanderthal fragments in different populations have been preserved approximately the same, and the "deserts" are all in approximately the same places. This means that these "deserts" are not an accident, they have some kind of biological meaning. If you study people from Oceania, it can be seen: "Neanderthal deserts" and "Denisov deserts" quite often intersect with each other.
And why are these fragments? Now some important piece of biology. I have told a piece of mathematics, now I will try to tell a piece of biology. Look, here's Dad, his chromosomes. Let's assume that we have only one pair of chromosomes, for simplicity. Dad has two chromosomes. Each of us has two copies of each chromosome. But, again, except for sexual, but there is no question about them. Here, accordingly, the mother, her chromosomes, are also a pair. And now they are combined in different combinations in children.
Where did these chromosomes come from? Each child has one chromosome coming from dad, and the second chromosome comes from mom. It's just the way cell division works. And, accordingly, this is how the fertilization process works. This is the paternal grandparents, and this is the maternal grandparents. Dad has one chromosome from the corresponding grandfather, another chromosome from the corresponding grandmother, and he gives each child either one of these chromosomes or the other. What does this mean? If we look here carefully, it would mean that no child can be similar in different ways to all grandparents at once. That if I look like my paternal grandfather, then I can no longer be like my paternal grandmother in some other way. And, accordingly, the same thing on the other side.
But it doesn't really happen that way. A grandson may be in some different details, signs similar to all of his grandparents at once. Why is this happening? Well, firstly, there are many chromosomes, and different chromosomes occur in different combinations. But there is an even more subtle molecular mechanism called "recombination", it consists in the fact that the chromosomes in this pair can break and reconnect at the ends. That is, we get a chimeric chromosome: it partly consists of a grandfather's fragment, and partly of a grandmother's. That's what happened to my father. And it happened to Mom. And recombinations happen often enough that the signs get mixed up. In general, this is a very important piece of biology. Recombination seems to explain why sexual reproduction is necessary at all, why it is impossible to simply divide like bacteria. The chromosomes are torn and swapped, so I don't have a whole Neanderthal chromosome. If there was no recombination, then I would either have nothing Neanderthal at all, or Neanderthal DNA would be whole chromosomes. And I have it in fragments on different chromosomes. And this happens because the chromosomes break during recombination.
This means that the fragments of Neanderthal DNA become shorter with each division. Their share, the share of the genome covered by Neanderthal DNA does not decrease, but the fragments themselves become shorter. And this means that by the distribution of the lengths of these fragments, we can judge when hybridization occurred. If all these fragments are very short, hybridization happened a long time ago. If these fragments are relatively long, it means that they have not torn so much, which means that hybridization has happened recently.
We have a wonderful Cro-Magnon femur from Ust-Ishim, it is in the Tomsk region. This ancient Cro-Magnon, who lived about 45 thousand years ago, already has Neanderthal alleles, about the same as ours, maybe a little more. Denisovsky – no. But these fragments are on average somewhere from two to four times longer than those of modern humans. That is, Ust-Ishimets is closer to the hybridization event than we are.
Then you can again write some equations and estimate when this introgression happened. If we know from radiocarbon dating of this bone that Ust-Ishimets lived 45 thousand years ago, and we know the distribution of the lengths of Neanderthal fragments in him and in modern humans, we can estimate how many generations have passed. And hybridization happened somewhere 50-60 thousands of years ago. Almost immediately after the ancestors of the Cro-Magnons came out of Africa about 70 thousand years ago.
You can take another ancient Cro–Magnon - from Kostenok, in Voronezh region. This bone was once unearthed, and for molecular research it was found in the Hermitage, where she has been living since twenty-such a year. It turned out that the man from the Bones has a little extra admixture of Neanderthal DNA.
That is, we have all these events starting to multiply, we see them more and more. In the history of the man from the Bones there were two hybridizations – common with everyone and their own, new. And this (on the slide) is a terrible, terrible riddle, about which I will tell you more.
And a little more side story, but interesting. There is an Oase cave in Romania, that is, the "cave of bones". There was found a bone, which is 40 thousand years, a whole jaw, about which anthropologists have long suspected that it was a bone of some kind of hybrid, because it combined the signs of a Cro-Magnon and a Neanderthal. And it turned out to be an amazing guy. His Neanderthal fragments turned out to be of colossal length, sometimes almost half a chromosome. This means that very few of these recombinations have occurred, and hybridization has occurred quite recently. And it can be calculated that his great-grandfather, or at least his great-great-great-grandfather, was a Neanderthal, only from four to six generations. To imagine this: Alexander Pushkin 's great - grandfather was Ibrahim Petrovich Hannibal, a native of Ethiopia, if I remember correctly, and this guy's great-grandfather was a Neanderthal.
This is a dead-end population, there are no descendants of them in modern Europe , but, again, another independent hybridization event.
You can see the proportion of Neanderthal fragments in these ancient Cro-Magnons. One study showed that the proportion of Neanderthal fragments decreases over time, which means that selection gradually washes them out, they are not very good. But another article was immediately published, which, on the contrary, shows that if you make an adjustment for a certain artifact, the proportion of Neanderthal fragments does not decrease over time. That is, it means that selection does not work against them, that there is nothing wrong with them .
And then begins this novel in genomes, which I promised in the title of the lecture. Because people sequenced more and more genomes of modern humans, the resolution of computational methods increased, the methods became more subtle, more detailed, and we began to see more of everything. It turned out that Denisov variants actually exist in the genome not only of Papuans, but also of East Asians, the same Chinese, just smaller.
The more data there is, the more complex scenarios it is possible to understand: what happened and when. It turned out that not only in the genomes of Cro-Magnons there are Neanderthal fragments, but also vice versa: in the genomes of Neanderthals there are Cro-Magnon fragments. Namely, not all Neanderthals, but the Altai Neanderthal.
Most likely, 50 thousand years ago, the child remained living with his mother and in the group to which the mother belonged. Accordingly, the very first descendant is a half–breed, then these Neanderthal fragments (if this is a Cro-Magnon tribe) gradually spread among everyone, average out, and everyone gets a little bit. This is pure arithmetic based on the very process of recombination. That is, apparently, Dad was a Neanderthal, met mom somewhere, mom happily got pregnant, returned to her relatives in her tribe, gave birth there, and there this baby lived and contributed to the gene pool of this tribe.
And sometimes the opposite happens: mom was a Neanderthal, dad was a Cro-Magnon. And everything is the same, just the opposite: they met again, everything happened, the Neanderthal mother returned to her Neanderthals, and this Cro-Magnon-Neanderthal half–breed - he also had some children of his own, grandchildren and everything else, and gradually now Cro-Magnon fragments began to spread across this Neanderthal tribe.
It could have been either way. And this is already quite a novel.
Two independent streams of Denisovan genes were found in East Asians, that is, there were also several hybridizations with Denisovans.
Thanks to the large amount of data, we can see which Neanderthal was doing all this, with which Neanderthal hybridized. These are European Neanderthals. Hybridization happened approximately 70 thousand years ago, after the European Neanderthals separated from the Altai, which was about 150 thousand years ago, but before the European Neanderthals began to separate from each other. There is also a separate story about early and late Neanderthals, God be with her for now.
Two years ago, a fantastic story happened in general. Another tooth from Denisova cave. We already know that it may be Neanderthal, or it may be Denisovian. And this one turned out to be in half. It turned out to be a wonderful girl whose mother was a Neanderthal, and her father was a Denisovan. This girl was a pure half-breed. These are not great-grandfathers, like that Romanian guy, but they are just mom and dad, relatives. That is, it is a hybrid of the first generation.
And then people evaluated the antiquity of various bones in the Denisova cave. We have four Denisovan individuals, three Neanderthal individuals; it is clear that they overlap very much – this girl, who 100 thousand years ago was the fruit of this connection. That is, they really lived in Denisova Cave, then one, then the other, then all together, in general, somehow it all happened very violently there.
Chagyrskaya cave, very close to Denisovskaya cave, also in Altai, a very recent article – May 2020. There is also a Neanderthal there, but he is absolutely not a close relative of the Altai Neanderthal from Denisova Cave. I said "Altai Neanderthal", and now it's clear that you can't say that, because there were at least two independent branches of Neanderthals in Altai who lived a little at different times, that is, the Chagyr Neanderthal and Denisov Neanderthal are not the closest relatives to each other.
We don't have Denisov skeletons. We don't know what they looked like. But what we can do: we can try to reconstruct them from the genome. What people have done: they took many, many modern people, identified variants of genes that affect the development of certain bones, certain fragments of the skeleton, validated it on modern people, checked that this prediction really works correctly, that we can determine the length of some bones, their mutual sizes, such by variants of genes sorts of things. Further , this was also validated on Neanderthals. Because we know both genomes and skeletons about Neanderthals. It seems to have worked too. And then they applied this technique to Denisov genomes, where there are no skeletons anymore. And here is a Denisov skeleton, reconstructed according to genomic variants. They even tried to draw a portrait of this Denisov girl, she turned out to be very unkind here, I do not know why.
If we take a human and take his Neanderthal variants, what signs can these variants bring? The hair color is understandable, the structure of the skin and hair is also understandable, the immune variants of our genes are Neanderthal – it is clear why: Neanderthals lived in Eurasia for a long time and adapted to local pathogens. And when the ancestors of the Cro - Magnons came from In Africa, then local variants of the immune system genes proved to be useful, and they spread well in the population. Carriers of Neanderthal variants of the immune system genes gained an advantage because they were more adapted to local pathogens.
There are a lot of all sorts of psychological signs – it's true just from this , it still needs to be sorted out – but it seems that according to various articles , the idea that Neanderthal gene variants predict whether a person will smoke, that is, that he will rather smoke, all sorts of depressions (well, this is related to smoking, apparently), sensitivity to pain is also a very recent article that some variant of the gene that enhances sensitivity to pain is of Neanderthal origin. Well, one of us. All sorts of stories related to metabolism, with growth – in general, we have a bunch of Neanderthal variants that bring some of their own variants. Here, according to various articles, it is possible to collect it, I have been doing it for a long time, I think that now this list would be much longer. Well, just what is true from this – it needs to be sorted out for a long time.
There is a wonderful story, I will tell it, it is absolutely wonderful. Tibetans. People live in Tibet, in the mountains. If one of us is sent to the highlands and also given physical exercise, then we will die, we will have a high-altitude illness, it is known to climbers, and the reason for this disease is this: the body feels a lack of oxygen, and the natural physiological mechanism of production of red blood cells – blood cells that carry oxygen, red blood cells - turns on. And since this is severe starvation, so many red blood cells are made that they simply clog small capillaries, and the person dies. And the Tibetans – nothing, they run there with their backpacks, it's fine. It turned out that this is why: there is an EPAS1 gene, it determines fitness for high altitude. In general, the Tibetans are genetically very similar to the Chinese. But this particular variant of this gene in Tibetans is completely different.
And so we see a very characteristic pattern in most Chinese, and we see a very characteristic and completely different pattern in Tibetans. It can be seen that some Tibetans still have this gene in the Chinese version, but most of them have a completely different one. And what is this wonderful option? And this is the Denisovsky variant. We see that the Tibetans have seized a variant of this gene from a Denisovan. And by the way, it's only from here, from Moscow, that Tibet, that Altai – the mountains are somewhere far away there. In fact, these are completely different places. And again, this means that Denisovans were not only in Altai, but also met with Tibetans somewhere , and the Tibetans grabbed a variant of this gene from a Denisovian, and it turned out to be terribly useful, adaptive precisely for the conditions of the highlands.
The trick there is that this connection between oxygen starvation and the production of red blood cells is broken. That is, Tibetans and Denisovans would probably be bad stayers, bad marathon runners, but in the mountains it turned out to be useful and good.
Then an interesting thing. Already another article. People took the genomes of different Tibetans living at different heights. And it turned out that the higher a Tibetan lives, the more he will have a share of Denisov DNA. Perhaps this tells us something about where the Denisovans lived.
Then it turned out (I have already mentioned this) that not only the Papuans have Denisov variants, but the Tibetans also had them, and besides , they were found among the Eskimos, and not ordinary, but Greenlandic ones. Where is the whole story with Altai and Tibet, and where is Greenland, right? There were two genes that a lot of people have, but the Eskimos (it seems they are supposed to say "Inuit" now) they also turned out to be very adaptive, almost all Inuit have Denisov variants of these genes. These are genes that affect a lot of things: the development of the skeleton, adipose tissue, the shape of the face – in general, a lot of things.
Which genes have ancient variants turned out to be bad? These are just the genes that are found in the "Neanderthal and Denisov deserts." These are mainly genes related to male fertility and the quality of sons in general. These are genes in which mutations lead to male sterility; these are genes that work in the testes; these are genes that live on the sex chromosomes, and this is all such a complex of genes that affect the quality of males. This means that the boys in these mixed marriages were so-so. Either there were dead boys at all, or boys, maybe there were nothing, but they could not have children. That is, this Neanderthal could be a man, could be a woman, but there was no hope that he would have good grandchildren through his sons. And through the daughters – as much as you want. That is, our Neanderthal fragments came mainly from the female line.
Well, then you can see which genes we have changed rapidly compared to Neanderthals. These are all sorts of genes related to learning ability, brain development and hyperactivity. It is also clear that our genome is not arranged in the same way as in the Neanderthal: for example, we had a duplication of the amylase gene (amylase is an enzyme that breaks down starch), this is an adaptation to eating all sorts of tubers and rhizomes.
Well, now... I kept hinting that so far what I was telling is just flowers, and the real terrible secrets begin only now. Here they begin. Terrible secrets are connected with mitochondria. Mitochondria are cellular organelles, they also have a very interesting history: these are former bacteria that turned first into symbionts, and then into organelles in general, completely lost their independence. And what they are remarkable for is that they have their own genome. These are short genomes, there are 17 thousand "letters" in total. There are 3 billion letters in the nuclear genome, and only 17 thousand in the mitochondrial genome, but each mitochondrial genome in each cell is present in a large number of copies. Each fragment of the nuclear genome is present in two copies, and each fragment of the mitochondrial genome is present in a hundred copies. Therefore , the dose of each mtDNA fragment per cell is greater. And this means that when we look at the highly degraded ancient DNA, the first thing we will pick up from there will be just the DNA of mitochondria.
The very first Neanderthal fragments that were identified were just mitochondrial. And another important property of mitochondria is that they are transmitted strictly through the maternal line. That is, only men have Y chromosomes, and they are transmitted from man to man, from father to son, and mitochondria everyone has it, but regardless of whether you are a man or a woman, your mitochondria will be from mom.
And you can watch, say, all sorts of stories about the diversity of mitochondria: for example, you can watch what happened in Europe about 50 thousand years ago. To do this, they took mtDNA from different remains and saw that the family tree of different Neanderthals could be considered. We see that young European Neanderthals are all close relatives to each other. They came from different places in Europe, but they are all very similar to each other. And the old European Neanderthals and Asian Neanderthals – they are much more diverse. This means that at some point 50 thousand years ago, the entire diversity of Neanderthal genomes in Europe disappeared. And then it began to arise anew from some rather small group. This means that most Neanderthals died out 50 thousand years ago. Only a little bit remained, then they settled Europe back. And in Asia everything was fine, in Asia both young and old Neanderthals – they are all quite diverse.
What terrible thing happened in Europe 50 thousand years ago? Glacier. This is just the time of the greatest glaciation. And living in a glacier is pretty shitty, especially for a Neanderthal. And here they all are, poor, then. Almost all.
But that's okay, it's so that you just get a little used to the idea of mitochondria and maternal inheritance. But this is already a horror movie, if you look at all the mitochondria together. The Khoisans were the first to separate, a large variety of Africans, a branch that wandered to Europe and Asia. Separately , the Neanderthals, who differ from us by about half a million years, but the Denisov mitochondria is completely different. That is, we know that according to the nuclear genome, Denisovans are the closest relatives to Neanderthals, but according to the mitochondrial genome it is not so at all. Denisov's mitochondria came from absolutely no one knows where. And it separated from other human mitochondria about a million years ago. Who lived there a million years ago? And this is just the time when erectus are separated.
Further, in Spain there is the cave of Sima de los Huesos, also a "cave of bones". In it, the oldest bone from which DNA has been isolated is about 300-400 thousand years old. This is also a large femur. And according to the mitochondrial tree, these were the closest relatives of the Denisovans. And according to the nuclear genome, it is normal, these are the closest relatives of Neanderthals. That is, we have a contradiction between inheritance on the maternal side and inheritance in general, in the nuclear genome.
This is actually a fairly common story, called "introgression", when some fragment of the genome after hybridization is fixed from one of the ancestors. That is, most of it is blurred and it is not visible, but some fragment is fixed. In classical economic breeding, this is continuously used.
And here introgression happened just along the mitochondrial genome. The same story happened with polar bears: polar bears according to the nuclear genome are a completely separate, independent species, and the mitochondria of all modern polar bears are from the brown bear. It is even known where she lived: 100 thousand years ago in Ireland. And if you take a fossil polar bear from permafrost and look at its mitochondrial genome, then it is completely different. That is, this mitochondria of the brown bear captured all the genomes of all modern polar bears. And it seems that the same thing happened with the Denisovans, at least with those we know.
Although there may be another explanation, which four years ago it was impossible to believe. It is possible that everything was the other way around, that the Denisovan preserved the ancient mitochondria from a common ancestor with a Neanderthal, and these people had the same mitochondria in Sima de los Huesos 300 thousand years ago. And a Neanderthal grabbed mitochondria from a Cro-Magnon. In 2017, when it was first published, I did not believe it at all, I found some inconsistencies in this article. And now people have done neat work, and they also looked at the Y-chromosomes, which are transmitted, on the contrary, on the paternal side, and "according to the latest orders of the party and the government," the picture looks like Neanderthals and mitochondria and Y-chromosomes came from Cro-Magnons as a result of hybridization. The nuclear genome, the usual somatic chromosomes, they have their own, everything is fine with them, but they have the Y chromosome and mitochondria from Cro-Magnons.
How could this happen and why? And this is just a consequence of the fact that the population was small, genetically, apparently, not very powerful due to inbreeding and small groups, due to weakened selection, and these sexual The Y chromosome and mitochondria in this situation turned out to be more powerful in Cro-Magnons. And as a result of positive selection, they gained a foothold in the Neanderthal population ; although there might have been enough random drift, this should already be considered. In any case, those Neanderthals that we see.
But, again, there are many such examples about mitochondria – polar bears, African elephants have the same story. But for the Y chromosome to be replaced as a result of hybridization is perhaps the first example, and this is an amazing thing.
And then complete immorality begins. Firstly, it turned out that African genomes also have a little bit of Neanderthal alleles. This is again a recent article, February 2020. How could this happen? There can be two scenarios. The first is some kind of ancient hybridization between some Africans, even before entering Eurasia, and Neanderthals, that is, this is some kind of flow of Cro-Magnon genes from Africa to Eurasia, which left its traces in the genomes of Neanderthals. Possible explanation number two is reverse crossing: it was the Neanderthals who interbred with the Euro-Asians, and then some of these Euro-Asians returned to Africa and the Neanderthal variants dragged back to Africa through themselves.
I said that the Neanderthal fragments in my genome can be determined by comparing my genome with the Neanderthal one. But in fact, this is not necessary. If there is just a fragment in my genome that I don't look like anyone else, it means that it is a fragment of some extraneous origin. Just compared to the average level of similarity in this area of the genome. And this idea can also be implemented algorithmically. And then we do this: we take a program that implements this idea – just let 's look at modern people, different individuals, see where they differ most from everyone else. Then we can validate this program on the same Neanderthals. That is, we first forget that we have a Neanderthal genome – we remember that there are Neanderthals, but we forget that there is a Neanderthal genome – we reconstruct these potentially Neanderthal fragments, and then compare them with the first method that the Neanderthal genome uses explicitly, and make sure that we reconstructed about the same thing, that is, the method works. And now let's apply it, for example, to Africans. And we will see that the South African Pygmies and the Central African Pygmies have some fragments that came from nowhere, they are not like any of the neighboring peoples in these fragments. And these are not rapidly evolving fragments, because all the other people in these fragments do not differ much from each other, but these tribes differ very much.
And then this idea can be applied in different ways, and it turns out that the Tibetans have a contribution in the genome from no one knows who, and the Indians, people living in India, have a fragment from no one knows who, and the Denisovans, as I promised, here they have this mysterious mitochondria, and also they have fragments of the nuclear genome, too, from no one knows from whom. And all this unknown who was divided with modern people somewhere about a million years ago. Then there were no sapiens, then there were erectus. From the classical anthropological point of view. A million years ago is the time of erectus. That is, some people separated from the common ancestors of all of us now – Cro– Magnons, Denisovans, and Neanderthals - a million years ago, and then different groups of modern people, including Denisovans, met with these unknown people and also hybridized.
This is fresh, the work of August 2020. People evaluated all these ancient contributions, made subtle programs, and they saw what? They saw that about 200-300 thousand years ago, Neanderthals picked up DNA fragments from Cro-Magnons. That is, this is what I was talking about: that this is some kind of ancient Cro-Magnon migration from Africa to Eurasia, which left no traces archaeologically, but left them in the genomes of Neanderthals. Approximately 1% of Denisov genomes do not originate from Sapiens, that is, it is generally unknown from whom, from someone left. And then, since Denisovans first hybridized with unknown people, with erectus, most likely, and then they hybridized with Cro-Magnons, with Papuans, they dragged this unknown DNA during secondary hybridization to Cro-Magnons. That is, Papuans have about 1% of the genome that is not Sapiens. Well, as if not direct hybridization, but through Denisovans.
Boris, have you learned something new?
Dolgin:Yes, of course. Many, many new things, I must say. Well, that is, the picture has been significantly enriched. It has been significantly enriched by the way the history of our crosses and, apparently, migrations looks like, and by methods, of course. A lot more methods were presented, and it seems to me that this is also very interesting for listeners as some kind of introduction to the methods used to figure out this kind of thing.
Gelfand: Yes, why I like to tell this lecture is the science that is happening right now. I said at the very beginning that the last slides I showed were the slides of August. And there are some things that fall away, some of what I told you can be modified after a while. There are some obvious contradictions in what I was saying, so a very attentive listener, in fact, could catch me a couple of times. But this is a normal life. Here you can still see what Boris said: here you can see not only how the history of history is arranged, but how the history of science will be arranged after a while .
Dolgin: We have a huge number of questions. I'm starting to talk about them. There is one off-topic, but related to scientific popularization, it will be at the end. I'll start with something that is directly related to the topic. "What are the bioinformatic features of working with partially fragmented DNA?"
Gelfand: What are the features… Well, first of all, it's terribly dreary. There's also the main problem with the ancient The fact is that these are very small doses, and the risk of contamination is very high. The false start of 2006 was due to the fact that just the DNA that flies with dust in the air of the room from the fact that someone sneezed there - you don't even have to sneeze in a test tube , it's enough to just talk in the room – is comparable to the amount of DNA that we have in the sample. There are some insanely super-sterile rooms being made in order to work with this DNA, worse than with some terrible pathogens.
On the other hand, this is a good thing, because by the degree of fragmentation and by the chemical modifications that occur, you can estimate the proportion of contamination in your results. Another side, purely bioinformatic: the fragments are all short, and it is clear that you cannot assemble a complete genome from such short fragments, so any genome there is actually restored by mapping these fragments to the reference genome of a modern person.
That's what we can't study – we can't study large genomic rearrangements. We can study them by comparing modern people, some translocations when a fragment jumped somewhere. We cannot do this with fragmented genomes.
And from a genetic point of view, of course, people have invented a bunch of new methods to detect all this hybridization. It's not really my area, really. I love her and I follow her, but I can swim on very technical details, but here's what you can see – that people have invented a bunch of new genetic tests, and such tests… Here's the specifics: any modern genetics works with the genomes of contemporaries. These are people who live at the same time. You don't have a time axis in normal modern population genetics. And in the ancient DNA, you have another time axis. You can take into account that someone is older than someone. And this also gives rise to a large number of purely methodical techniques that work directly with this. Well, here are the corrections I was talking about: does the proportion of Neanderthal fragments decrease over time or does it not decrease? There the time axis is clearly involved.
Do you know what it looks like a little bit? This is similar to how viruses are being studied now by these terrible ones of ours. There, too, not only the sequence itself is essential, but also on what day it was taken from the patient. The methods are completely different, but this feature is really quite funny.
Dolgin: "How can the effects of Neanderthal gene variants be studied? Paabo seems to be doing GMO mice with human gene variants. Do you think this is a reasonable study?"
Gelfand: You can do this. You can do more on cell lines. It's not very clear what kind of control is there, because if you drag a human gene into mice, then the main shock there is that it's just not mouse, and it's Neanderthal or Cro–Magnon - that's the next question. But what I was showing, anyway, is just classical genetics. You have a connection of gene variants with some physiological, or anatomical, or psychological features that you see simply by classical genetic methods. And then you see that some of these variants are of Neanderthal origin. Here what I have shown is not experimental work, it is classical genetic work, just taking into account the fact that the variants may have such an unusual origin.
Dolgin: "Why Are there no world-class paleogenetic laboratories in Russia yet?"
Gelfand: And why is there not a lot of world-class science in Russia at all? Well, firstly, there are actually two or three such laboratories all over the world. And this is Paabo and his students, mostly. This is a very heavy equipment. This is the first thing. The second thing is that in Russia in general with great biology… There is a good biology in Russia, of course. But so that Russia has the same great biology as great mathematics and great physics – there has not been such a thing since 1948, since the famous session I remembered when the development of biology just stopped for 20 years. Moreover, these were critical 20 years when modern biology was being formed. And we still haven't overcome this gap. Well, then I can discuss in detail in general the state of science in modern Russia, but this is the topic of another lecture.
But, on the other hand, Russia is a great raw material power. We position ourselves as a raw material power. And in all these articles about Neanderthal DNA, quite often there are Russian co–authors exactly like the producers of raw materials - these are the people who dug up the bones and brought them. And already there , the third redo and the fourth redo are no longer ours, we participate in these articles with the source material.
Dolgin: " Are you interested in research related to later periods? For example, the Mesolithic population of Europe was dark-skinned, and before the Bronze Age it also did not digest lactose."
Gelfand: I understand. No. This is a very interesting science about the reconstruction of a younger history, population genetics, there are also a lot of wonderful things done with old bones. For example, the last thing I know is that they did understand which archaeological culture was the native speakers of the Proto–Indo-European language. There were many different theories, but now everything is tied to the pit culture, and it seems to be tightly tied. It was one of the three main theories, but it seems to have defeated everyone now.
Vyacheslav Vsevolodovich Ivanov believed that the yamnaya culture is the secondary homeland of the Indo–Europeans, not the main one. He wanted them all in the Front Room Asia should be planted according to linguistic reconstruction. I just found this book, a two–volume book by Ivanov-Gamkrelidze, by chance and reread it. And they just mention the Yamnaya culture, but as a secondary homeland of some Indo-Europeans. And it looks like it was her.
There are some wonderful stories about how agriculture was promoted in Europe. I am interested in this, but I don't know how to give lectures about it, because this is a very large separate area, there are people who know it much better than me. I did participate in some Neanderthal works, and this is just another field, colossal, with completely different methods and very interesting, but I don't know how to talk about it well.
Dolgin: Another question from the same author is related to lactose in a number of Asian peoples, with the impossibility of processing and at the same time with the active use of fermented milk products. More precisely, the question simply talks about dairy products, but they are listed further, of course, fermented milk.
Gelfand: Well, look, it's a well-known thing that people who can't drink milk can drink kefir at the same time. Because fermented milk bacteria, namely lactococci and lactobacilli, happily devoured this lactose, and now you can eat. This is a well-known effect that fermented milk products are better absorbed by people with lactose intolerance. But, again, I know this a little bit from the general culture, but this is not my specialty. But in principle, I think I answered. This is rather a question not about genetics, but about microbiology. It's the bacteria that digested it all.
Dolgin: "Humanized mice with human FOXP2 seem to squeak differently. And how else to study the effects of Neanderthal alleles? In public, you can't. They are trying on organoids, but there are not many publications yet."
Gelfand: It 's a question of what effects you want to study. If you want to study psychological effects – well, probably, yes, you will have to torture mice, but probably monkeys are better. Because the fact that these mice squeak differently - I would carefully examine these works… I'll explain what's the matter: there is a FOXP2 gene that is responsible for the development of speech. And people with a mutation in this gene are dyslexic, but at the same time their thinking is preserved. I don't even understand how this can be, because I'm used to thinking that people think through language. But that's how they write about it, anyway, I'm not a psychologist, I do not know what is meant. Neanderthals have the FOXP2 gene the same as us, if I remember correctly. But the whole area around this gene is a "Neanderthal desert", that's what I mentioned. That is, it seems that the Neanderthal version of this whole area was bad for modern man. And, naturally, it comes to mind at this point to start waving your hands and saying that Neanderthals had speech arranged somehow differently. What does this mean: that it's not about the protein sequence itself. (I can lie a little now, I don't remember this story well.) It seems that the gene is the same, but the regulation of this gene is different, it turns on and off a little differently. Just like with lactose, in fact: there, too, the matter is not in the variant of the gene itself, but in the regulatory variants.
And then, yes, there were some works about these mice that start squeaking in a different way. There this gene is interesting, birds have it, and there it also somehow affects how songbirds learn to sing. It works in the head, somehow determines the germination of neurons to each other.
That is, it seems that this function of the gene associated with speech, with communication, is a very ancient history, and then you can really put it in mice and see what changes. An interesting question is what will happen if the Cro-Magnon variant is transplanted to these mice. Surely such control was done, but I suspect that these mice also squeak differently. Maybe not so different, but... you need to watch the original article. I saw her, but I don't remember.
And if you want to watch some simpler cellular functions, something unrelated to the psyche, then you can do it on cell lines , please.
Dolgin: Many viewers are very actively thanking you. "Thank you for the excellent lecture, it has expanded significantly since the reading at the Scientific Station. Unfortunately, not all slides have a reference to the articles. Is there any way to get a complete list of articles? I want to read more."
Gelfand: Oh, I may not have made links on some old slides. You know, you can just search for it by keywords. I'm not picking them up now either. But in the most extreme case, if there really is no way, but you really want to, write to me, I'll try to find them. Then I need a slide, and I'll try to find the source for it. At the same time, by the way, I will plant it in a slide, in this sense there will be some benefit. It's just necessary to write me a letter, and it's easy to do, because in any of my articles and in any place of my work there is my mail, they are all equivalent.
Dolgin: " Is it possible to assess patrilocality/matrilocality in Denisovans by mtDNA diversity?"
Gelfand: It is impossible for Denisovites, because there is no diversity: we know them from the same cave. More precisely – again, I had it somewhere on a slide, I missed it - a couple of years ago a Tibetan bone - also, in my opinion, a jaw, if I remember correctly, a half of a jaw – was found in Tibet quite a long time ago, it was kept in some monastery, then it was they were transferred from the monastery to the university, and when the hunt for Denisov bones began, there was no DNA in this bone, but there was enough collagen protein to analyze by another method, to determine the sequence of not DNA, but one specific protein, and it turned out to be Denisov's, this jaw. This is the first direct proof of the existence of Denisovans in Tibet. We know this because Tibetans have Denisovan DNA fragments, I told you about it, but this is direct proof, just a bone lying there.
I have already said about patrilocality, I mentioned it, I did not say in detail: these are the Elsidron people, there was a whole family group, and there was one DNA in adult men, and the other DNA was in women and children. That is , it means that the women came from some other groups and, accordingly, the children were similar to them. Mitochondrially. In any case, this is how it is interpreted. There, if you start writing a novel and think how it could be, then it is clear that this is not a very stable situation, because then mtDNA must change in each generation. There, in general, everything is also not very clean with this, to be completely honest. Denisovites don't have this, because we don't have family groups . We have individual teeth that are tens of thousands apart years, and that's it.
Dolgin: " Please recommend a good book that allows you to dive into population genetics in an accessible form."
Gelfand: I don't know any good popular books about population genetics. But this may be a consequence of my illiteracy, again, because I do not follow population genetics closely. It's just that there are wonderful books about evolution Alexandra Markova, the whole series, in particular, about the origin of man. Well, in general, there are a lot of good books about evolution in general – Eugene Viktorovich Kunin is a wonderful book. About ancient DNA – this autobiography of Paabo...
With ancient DNA, there is also a wonderful science about the history of domestication. Because the same thing can be done with ancient bones of cows, horses, dogs.
A terrific plot: dogs were domesticated several times, apparently independently (this is something I followed at least a little). There is some history of domestication of cattle unfolding. In fact, there are still a lot of wonderful stories about this. And, again, I haven't even seen good reviews about it , to be honest.
About population genetics, I can say that it is necessary to look. There is a Gene Pool website.the Russian Federation, which is led by wonderful people at the Institute of General Genetics – Nadezhda Markina, in particular. It's not like a book, it's news. But there, firstly, they are well selected, and secondly, they are clearly stated.
Therefore, if you are interested in modern population genetics in its historical aspect, you just need to look at the Gene Pool.the Russian Federation should go and read articles there more or less in a row, probably. You won't get a general picture, but the mosaic will be very funny. And in fact, no one has a general picture . In this sense, we are all in the same boat with you.
Dolgin: Question from Evgenia Lysakova: "Does the X chromosome of modern humans contain Neanderthal snips? In recent hybrids, like that Cro-Magnon, they tried to estimate the length of Neanderthal sites..."
Gelfand: Look, these are insidious questions from people who know better than me. It's such a good way to learn everything, and then go to torture… I'm going to Google who Evgenia is Lysakova, don't think about it... Maybe it's an employee of the Institute of General Genetics of the same.
Look, in principle, there are "Neanderthal deserts" in the X chromosome, there are significantly fewer Neanderthal snips there than in somatic chromosomes. And this, again, is interpreted as a sign of that very male sterility. There seems to be a certain amount after all. But the density of Neanderthal variants on the X chromosome is significantly less than on somatic ones. That's the last thing I know about it. There didn't seem to be any bright articles about it . If there was something outstanding, I think I would have noticed.
And in principle, there is a very funny story with Neanderthal snips. Here I was asked how we know all these Neanderthal variants – but from where: it's just that all the people who were engaged in the genetics of a particular disease, specific physiological systems, immediately rushed to look for mutations among their mutations, not mutations in fact, but Neanderthal variants. In the 2010s there were a lot of articles that "we've been doing genetics of something all our lives, and now let's see if Neanderthal variants will explain it all to us." And there were dozens of such articles. I haven't looked through them all because I don't have the strength. If someone looks through them and writes a big review with a big beautiful table, he will be happy and grateful from the admiring humanity.
Dolgin: Two related questions. "Mikhail, I would like to clarify: is this interspecific or intergenerational hybridization? And I would like to understand if there are similar examples of hybridization among modern monkey species", "Contacts between different species could be voluntary and long-term, or were they usually violent?"
Gelfand: Listen, the answer to the second question is – it depends on your imagination. With regard to people who lived 50 thousand years ago, I cannot imagine how voluntariness and violence are arranged there in general, and how the concept of sexual harassment is arranged there at this time . But there didn't seem to be such a thing that there were just mixed groups. The devil knows, it's unclear how we would actually see it. But judging by how… You see, there is a small proportion of the DNA of the other parent in each genome . This means that they could have accepted someone into the tribe. But this does not mean that two independent tribes lived side by side and regularly exchanged brides and grooms. There is no such thing.
Dolgin:That there is this episodic, not systematic.
Gelfand: To what extent it was voluntary, no one will really say, but what exactly did not happen was such a free, long–lasting exchange of genes between two neighboring groups (they would have mixed up more). These are quite unique events. Frequent, but quite unique. Why do we know that they are frequent? Look, out of twenty ancient genomes, two of us have traces of fantastically recent hybridization: this guy from Romania, and a girl who is half Neanderthal, half Denisovan. Now look, if you go into a city and out of twenty passers-by you see two mulattoes, you think that in this city everything is OK with racial prejudice. Just purely for statistical reasons , it is clear that these events occurred frequently, because of the few genomes that we know about, this has just happened twice. But people don't seem to see a constant flow of genes. This is the answer to one question.
The answer to another question is how exotic it is, whether there is any special human miracle here. No, because mammals have such examples. Here I can refer to my review in the magazine "Nature" about five years ago, I have collected a small collection of such cases there. Two of the most beautiful examples are these polar bears, who 100 thousand years ago seized mitochondria from brown ones. Well, and besides, we know that they interbreed wonderfully in zoos: there are photos of hybrids of a white and a brown bear.
And the second example is very beautiful – these are savanna and forest African elephants. There savanna elephants are larger, and at the border of the area where they meet, their mitochondria are increasingly from the forest. And there is some legend that savanna males prefer forest females for some reason, or forest females prefer savanna males because they are larger. In general, there are a lot of elephants in the hybridization zone, which, according to external signs and the nuclear genome, are like savanna, and mitochondrially forest. They interpret it as who likes who more, who is more successful.
The question of whether it is a single species or… Well, this is obviously not an intergenerational crossing, because it is a genus Homo, in this sense it is not that insanely distant crossing. Whether to consider Neanderthals and Cro–Magnons as one species or different is a largely scholastic question, because, on the one hand, they had fertile offspring, we clearly see this. On the other hand, still not quite, because the girls were fertile, and the boys were not fertile. And this is a classic story when hybridizing close species – when we hybridize close species, the heterogamous sex, that is , the one with different sex chromosomes, like in mammals X and Y, suffers more from such close hybridization than the homogamous sex, which has XX, like in female mammals. In this sense, people are no different from everyone else. But whether to call such a situation one species or different, when there are offspring, but still a little crooked, is whatever you want. This is exactly the gray, transitional zone, when there is no longer exactly one species with free crossing, like, say, different populations of people, but not that completely different species with asexual descendants, like horses and donkeys. That's exactly in the middle.
Dolgin: I see. But in fact, can we say with certainty that the male descendants were infertile, just because this option seems to be losing evolutionarily?
Gelfand: No, well, I said it a little sharply. I said that they were infertile – they were rather with reduced fertility, it is necessary to speak mildly. There were fewer and fewer grandchildren through the male line.
Dolgin: I see. And if we imagine that, after all, some small communities had mixing as a local norm, but it simply did not turn into a global norm, and when communicating with other communities, it was blurred? Could it be like that?
Gelfand: Listen, well... how can we find out?
Dolgin: So I'm trying to figure out if we can find out.
Gelfand: We have five genomes. If we have a hundred Neanderthal genomes from different places – or rather, even I, as an optimist, say not "if", but "when" – when we have a hundred Neanderthal genomes from different places and if we have a hundred Denisov genomes from different places, then we can try to answer these kinds of questions. Now we still have too jerky initial data to distinguish between these scenarios. Again, this is not my area, but I absolutely don't see how we could find out.
You see, it could have been anything. Neanderthals and Denisovans could live happily in the next cave for 100 thousand years, I can't mix up to the most, and we just don't have a single genome from there, that's it, hello!
Dolgin: Well , yes, I understand. "There is a question about left fragments and hybridization with whom it is unclear: and how to distinguish such hybridization from a situation when a fragment was inherited from the ancestral population of erectus, which was then lost in the majority? It is clear that all sapiens are monophyletic, the question is how real they were..."
Gelfand: Yes, I understood the question: how real is such a long-lasting polymorphism that lasts in the population for half a million years. Well, it seems to be considered that it is not very real. In the article in which they wrote about it, they take this into account, they always take into account the probability that there is just a polymorphism that holds in the population. But look, no polymorphism in the population can stay at a low frequency for a long time: it is either lost, or due to drift it grows and is fixed. There cannot be an option that is not adaptive, does not affect anything in any way, and that's how 1% holds on, holds on and holds on. This is a terribly unstable situation. If you have a million rubles, then you may have two million in some successful years, and half a million in less successful years. But you can still exist for so long. If you have a ruble and you have lost it – that's it, you won't take it from anywhere else, you've already starved to death. A variant that dangles with a small frequency will simply hit zero, and this is what is called a random walk with absorption: they no longer return from zero. If the option is lost, it will not come from anywhere. Random wandering around small frequencies is terribly dangerous. A drunk can safely walk on the plain, but it is harmful for a drunk to walk along the cliff. And random wandering is just called the "drunk problem". Well, of course, the drunk takes a step to the right-to the left.
Dolgin: The question I promised, not directly related to the topic, but related to the popularization of science: "How do you develop mutual understanding with scientists from other fields? We have repeatedly come across statements by Drobyshevsky, Derevyanko, and Zatevakhin that do not correspond to genetics."
Gelfand: I do not know Zatevakhin's statements, I do not follow them, and, in my opinion, he is a zoologist after all. I am reserved about Academician Derevyanko's statements, because Academician Derevyanko's contribution to all this science is not even that he dug up all these bones himself, but that he, as the director of the institute, allowed them to be used. There are other people working on the expedition. This is purely my opinion from the outside, I don't know the details, but I have a feeling that this is just a classic example of an administrative author. And with Stas Drobyshevsky, the story is like this: I am not an expert in anthropology, so I am not ready to comment on his anthropological statements, and many of his statements about molecular evolution in books and elsewhere are just nonsense. And moreover, unfortunately, an unpleasant situation happened with Stas when I criticized some of his book among my own, I was invited as a scientific editor to the second edition of this book, and then some edits were ignored, in my opinion, quite important; in general, I had to remove my last name from there, there was an unpleasant story. Therefore, I have a relationship ... well, with the first two , my relationship does not develop in any way, because I do not speak about them, and I hope they do not know about me, and with Stas we have serious disagreements on specific issues of molecular evolution. Well, again , neither he nor I are experts in population genetics, but I'm still not an expert, because I tried to understand the methods carefully, too. Well, and even did a little something.
We have been through this many times, in fact, in our science. There was a wonderful story about hippos being the closest relatives of whales, and there were also terrible battles between classical zoologists and molecular taxonomists. Two years have passed, and everything has become clear. Another thing is that in those works that I retold, there are also a lot of contradictions. Well, actually, I 've already talked about it. This is such a normal living state of science, when people get different conclusions by different methods, when new genomes are very much, well, not inverted, but very much added. This is a real scientific life, it should be arranged like this, by and large. But some basic things are not going anywhere. That there were hybridizations, that there were a lot of them, that there were Denisovans – that's not going anywhere, that's all, it's like the law of universal gravitation. Details, specific scenarios – I made a reservation several times in the lecture and now I will make a reservation again: come back in five years, something will be different.
Dolgin: Actually, this is what distinguishes science – the fact that constantly new data… She is not afraid that new data will force her to find new generalizations.
Gelfand: Well , yes, this is actually a sign of a normal living and healthy science, it's true.
Dolgin:Thank you very much. I think it was wonderful.
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