Mammals, by and large, differ from each other not in the set of genes or even gene variants, but in when they turn on and off. In fact, people understood this in words for quite a long time - at the level of hand waving. But for half a century it was such chatter, theoretical, and for the last ten years you can touch these things with your hands, look with your eyes, put them into a computer and start comparing. Unfortunately, it's very expensive to do this well, but it gets easier. In the first article about transcriptomes of single cells, there were, in my opinion, about three hundred of them, and it was an article in Nature. And now in normal articles there are thirty thousand of them - or already three hundred thousand.
You can make genomes of single cells and, for example, look at the phylogeny of neurons. What would be a naive picture? Well, there is a brain, and in each part of the brain the neurons are relatives to each other, because some cell divided and its descendants formed this part. It turns out that there is nothing of the kind: neurons that are located in one place are genetically very distant relatives of each other. So distant that their common ancestor may not have been a neuronal precursor at all, but some earlier cell. And their functional identity is determined by the place they ended up in.
In hindsight, it is clear that this was a very correct engineering decision. Why? Let's imagine that a region of the brain is the descendants of one cell. This means that if during the process of ontogenesis this cell accidentally died, then an entire area has disappeared, because the cells that should have developed from it did not appear. And the situation when the identity of a neuron is determined by where it ends up is much more stable. Because even if some cells randomly die during ontogenesis, and this is inevitable, others take the place of their descendants. This is much more stable than a rigid hierarchy.
Another useful application of cellular phylogenetics is reconstructing the history of cancer tumors. These are the same wood methods. You can see in what order the mutations appeared, how the clones differ, and what the origin of the metastases is.
Thus, the scope of application of molecular trees is actually much wider than it seems at first glance. Let's say embryology at the genome level - that is, which cells come from which. This can be complemented by transcriptomics to describe the differentiation of cell types and tissues. Cancer phylogeny is a reversed embryology, dedifferentiation, regression to early cell types.
— Is it possible for anyone in Russia to make transcriptomes of single cells?
— In Russia they work with single cells, although in few places. Colleagues from the Institute of Gene Biology made the chromatin structure in single Drosophila cells; We then processed this data with them - and we got a good article.
Then - this is my favorite story - it turns out that in insects with complete transformation in the pupa, the transcriptional program of embryo is reproduced. Not as brightly as we would like, but it works a little. So evo-devo, something people have wanted for a long time, can now be done arithmetically.
“The question turns from a scholastic one into a purely computational one”
— If we return to general biology. I asked everyone: have the criteria for the species changed? In general, what are considered species? And there was a general consensus that species are certainly a reality, but the criteria for species are being blurred.
— Well, are Neanderthals a separate species or not?
— Well, there are different opinions. But crossing occurred.
— Crossbreeding took place, but the boys were dead.” It was successful because we are his descendants, but it was also not entirely successful because the male hybrids apparently were poorly fertile, and we also see this in genomes.
— And how can we answer the question of whether this is a separate species?
— This problem has always been there, only it was solved at the level of conversations. And now some quantitative estimates are possible for it.
— I tried to bring everyone to quantitative assessments.
— There is a classic definition that I heard from Alexey Simonovich Kondrashov: a species is a set of individuals between which there is a free exchange of genetic material.
— It happens that groups in nature are isolated, and free exchange does not occur, but if they are “put in one bucket” (not my expression), then individuals can reproduce.
— There are many different experimental designs. For example, you put a male of one species and a female of another together, and they begin to reproduce because they have nothing to do. And if the female had a choice, she would take a male of her own species, but would not pay attention to him. This is a classic thing: there must be an experiment with competition. Second option. There are equestrians, two different species, they do not interbreed at all - they do not produce offspring. But they turn into one species if they are fed tetracycline, because Wolbachia does not allow them to interbreed. In general, there are always gray areas in biology. There are understandable extremes and there are more or less broad transitional situations. A normal biologist approaches this without neurosis.
— Zoologists are looking for a quantitative level of molecular differences that could serve as a criterion for a species. And it is different in different groups.
— Absolutely right. It is different in different groups, and a person differs from a chimpanzee by one time by 100 letters, and two specimens of Drosophila also differ from each other by one time by 100 letters. This means, from the point of view of Drosophila, humans and chimpanzees are one species. But there are no offspring, it has been verified: enthusiasts were engaged in this business a hundred years ago.
In principle, for each family it is possible to gather people who work on it, and they will decide that, say, in beetles we distinguish one species with such and such similarity of such and such a gene, and in butterflies - with such and such similarity of another gene ... But, firstly, I don’t really understand how this will be useful - this is still not a substantive, but a technical definition. Secondly, there will still be a lot of exceptions, because in biology there are always a lot of exceptions, and taxonomists will still argue. Thirdly, this will actually have to be done separately for each taxon, which in itself, in my opinion, is very ridiculous. There will be a thick reference book: in such an order, a species has so many percentages of similarity for such a gene, and in another order, a species has a different number of percentages for another gene. And on each page there is the seal of the corresponding department.
The correct approach, but orders of magnitude more expensive, is to sequence the genomes of a noticeable number of individuals of one and another species, and then see if there is a flow of alleles here or there. If there was no flow of alleles, then these are different species. If you see that they have hybridized many times and continue to do so, it means that they are one species, then you can divide them into subspecies as you wish - that’s what they just did with the Far Eastern tigers: they divided them into subspecies according to genomes. It is clear that in the overwhelming majority in most cases there will be no money for this, but for some important and endangered species it is necessary to understand the genetic structure of the population, in particular, in order to correctly plan protective measures: to preserve all subspecies, but not to mix them.
Returning to evo-devo. We understand that changes in regulation that alter morphology and physiology are essential for speciation. They also occur as a result of mutations, but the proportion of such mutations is small. Therefore, defining a species based simply on sequence similarity is not even very good conceptually, because it measures the time of divergence of populations, but not the substantive differences.
There are classic cichlids in African lakes; They undergo explosive speciation, and at the same time they interbreed freely. That is, they just don’t interbreed freely - they don’t want to - but if they are not given a choice, then they will interbreed, and the result will be an ancestral form, a gray one. Since the species there are very young, they are genetically and sequence-wise very similar, but morphologically they are quite different. Again, this means that some specific genes work a little differently in them. Therefore, for example, the shape of the mouth turns out to be different, and in the end someone is a scraper, someone is a predator, and someone is a picker from the bottom or from the surface. And the colors are different - it is important that boys and girls recognize each other, and not others. But at the same time they hybridize quite strongly, this is visible.
— But this does not prevent them from being considered species.
— I don’t care... I asked the zoologists another question. The species are okay, we will at least somehow define the species. What is genus? And all other taxonomic levels? The most honest zoologists say that yes, of course, the rest are just constructs that we make for convenience. On the one hand, yes. On the other hand... Let's say what an order is in mammals - this is quite clear (except for really some special cases, like with whales). And it’s clear why. Apparently, because at some point they all diverged very quickly. Mammal orders collapse around 70 million years ago. This is a situation like that of a dill inflorescence - a one-time division into many branches, then another - a clear hierarchy. Another option is with rowan: the branching in the inflorescence is chaotic, but the output is still an umbrella. Therefore, if the world were structured like a dill umbrella, then we would have childbirth, families, everything would be fine. If the world is structured like the umbrella of a rowan tree, then there are no genera or families, and we can only formally say that 50% of something is an order. Why 50%? Because it's convenient for us.
The tongues seem to be structured like dill. I asked linguists, there really is a concept of a language family, it is reasonable, families of approximately the same level of division. And there are no full-fledged hybrid languages (pidgins don’t count).
Generally speaking, this could be watched, I even know how. What is the difference between dill and rowan? If we project the branching nodes of dill onto the axis that runs along the inflorescence (that is, onto the continuation of the stem), then we will have points at which a lot of branching nodes are projected. And if we project the rowan onto an axis that runs along the inflorescence, then we will not see anything like that, because the branches will be chaotically scattered along this axis and there will be no condensations.
Why are mammalian orders good? If we take the tree of mammals and project it onto the time axis, then we see a very large condensation at the moment when, in fact, the current orders were formed. And this means that the order of mammals is a reasonable unit, completely objective, with which one can operate.
That is, in fact, the question of whether a high-level taxon exists meaningfully or is it a purely technical construct without any content is resolved this way: we take a tree, project it onto the time axis and see if there is condensation.
— With Elena Temereva, professor of the Department of Invertebrate Zoology, Faculty of Biology, Moscow State University, in “Conversations for Life” you talked about the Cambrian: if many, many organisms arose in the Cambrian at once, then they can be considered the ancestors of types.
— This means that types also exist. The question turns from a scholastic one into a purely computational one. We may not be able to do this for some reason, but at least we can perform a thought experiment.
— I have another unexpected question. Why do you think plants need such complex genomes? It seems that they do not have to solve such complex problems in life as animals do - movement there, learning...
— Who said that these genomes are complex?
— Well, first of all, they are very big.
— And the amoeba has even more, what now? A large genome is not good; a large genome means that selection is ineffective. In addition, we need to look at what functional classes of genes plants have. Let's say they have a more complex metabolism, they produce a lot of secondary metabolites, because everyone gnaws on them, but they cannot escape, and they need to defend themselves with some kind of chemical. And in general, they need genes for all occasions, because they can’t eat anyone, which means they have to synthesize everything, and they have to endure stress, because you can’t hide.
On the other hand, complexity in our sense is behavioral reactions, and this does not require very many genes. This requires a flexible regulatory system. Again, the germination of neurons - you need to follow some general engineering principles, due to a not very large number of genes. And then it works out on its own.
Now an interesting question is formulated, the answer to which I do not know: what happens if we compare the complexity of regulatory networks. It may turn out that our regulation is largely combinatorial, and therefore a lot of regulatory genes are not needed, but different combinations of their products are needed. But for flowers it can be flat, when each condition requires its own separate regulator. You just have to watch it.