Suicidal altruists

Mikhail Gelfand: "We will come to a better understanding of why mice are not fish, and fish are not mice"

Bioinformatician Mikhail Gelfand tells what evolutionary significance suicidal altruists have in nature, what a person can read from DNA and why the cells of the body are identical and their functions are different.

Editor-in-Chief of PostNauki Andrey Babitsky talked with Mikhail Gelfand, bioinformatician, Deputy Director of the Institute of Information Transmission Problems of the Russian Academy of Sciences, about the modern theory of evolution.

– Mikhail, what is the most interesting and incredible thing in the scientific part of your activity?

– Progress in biology is associated with progress in experimental technology. Now it is based on the fact that it has now become possible to quickly and cheaply determine the sequences of nucleic acids. A large number of protocols are based on these experimental methods, which tell us how all the genes work at once.

Moreover, processes such as translation and binding of regulatory proteins in DNA can be viewed not on average for a population of cells, but to describe the work of genes in individual cells. And then we have a completely different view of embryology, because we look at how progenitor cells become cells of a specific tissue or organ. You can take a mouse embryo, divide it into individual individual cells and watch the trajectories of changes in these cells and the appearance of tissues. That's probably the most wonderful thing.

– If we imagine that the proteins surrounding DNA are some kind of complex device, then there are probably some interesting adaptations in this device that allow you to control the DNA – RNA-protein system (the central dogma of molecular biology. – Ed.)?

– Such a system is different in organisms of varying degrees of complexity. A single cell of the infusoria, which is self-sufficient and knows how to do everything it needs, is much more interesting and more complex than any of our cells, because our cells are specialized and know how to do one thing.

– What influences it?

– Where DNA is looser, genes work more intensively, and where DNA is packed tightly, genes are silent. There is a funny paradox: the genome in all our cells is the same. However, as always, there are 5% exceptions in biology. But we can talk about the human genome, ignoring the differences in the genomes of individual people. And we can also talk about the genome, neglecting the differences between different cells of the same organism. In all cells, the genomes are the same, and the cells are different. And different cells form tissues that work differently. It turns out this way because different genes work in different cells. But at first, all the cells were one fertilized egg. And the first few cell divisions in the development of the embryo of the cell are absolutely identical. And then they acquire individuality and gradually differentiate into different cells and tissues. And when we look at how DNA is packaged or how genes work in single cells, we begin to understand the differentiation process much better.

– Is he becoming predictable for us in some sense?

– I would be careful not to speak out about predictability. But, in any case, we can try to describe it with much more details and from a much more general point of view. In the next five years we will have a breakthrough in embryology, because it will be possible to compare cell development programs of different animals. And then we will come to a better understanding of why mice are not fish, and fish are not mice.

– And how is such a program created?

– It's all written in DNA. We can see how the initially set gradient of several proteins in different parts of the egg includes different development programs and how gradually the egg learns where it will have a head, where it will have a tail.

– Is it possible to take an amoeba and make a tendril, a wing, an eye out of it, if it initially knows how to do everything?

– No, she knows everything she needs to be an amoeba. But she doesn't know anything of what it takes to be a fruit fly. Another thing is that there are, for example, such wonderful amoebas that can become a small fungus. They are called "dictyostelium". When they feel good, they are ordinary amoebas. When you get hungry, it's clear that you need to turn into a dispute, surround yourself with a dense shell and hope that the wind will take you to some good place. The following happens: these amoebas slide together and form a fruit body. After they have slid down, the fate of the cells that remained in the leg and the fate of the cells that remained in the hat are different: those in the hat go into sporulation, and those in the leg die.

– They know that they are suicidal altruists. Why don't they try to fight for themselves?

– The problem is that if everyone goes into sporulation at the same time, they will die halfway, because there will be nothing to eat. Therefore, some organisms commit suicide, and the rest feed on what flowed from those who died. These nutrients are enough for them to form full-fledged spores. The mechanism of suicide is regulated at the level of concentration of one protein. Moreover, in an individual cell, the concentration of this protein changes stochastically, due to random on-off. If you don't have enough of this protein, you will die.

There are cheater organisms that break the mechanism of random modulation and fix the protein level at a high level. Why does all this work evolutionarily at all? Because all these populations are clonal: all cells are genetically identical. And they are all descendants of the first spore that survived in the previous colony. If cheaters have formed in some colony, then they have a much greater chance of surviving and forming a new colony. The problem is that the whole new colony will consist of cheaters. And this mechanism will not work: no one will sacrifice themselves. It is clear that in more complex beings altruism is arranged in a much deeper way. But this model shows that in order to explain altruism, it is not necessary to involve higher forces, morality, and so on. Altruism can occur in unicellular creatures, and in form we will not distinguish it from the noble suicide of Alexander Matrosov or anyone else.

– Do I understand correctly that if some genes are actively read, and some are packaged and archived, then they have different levels of significance?

- Yes. We know that there are beneficial, harmful and neutral mutations. Most of the individual differences between people are differences that don't seem to affect anything at all. But this is just the classic idea that most differences are not really good or bad, but neutral.

For example, there are areas in DNA that regulate the work of genes. So, some kind of protein senses a change in conditions. Regulatory proteins sense changing conditions and bind to DNA in certain places. And after they have bonded, those genes next to which they have bonded turn on or off. And the places where regulatory proteins bind are very important. You can, by writing sequences of intergenic sites under each other, see conservative islands in which the sequence persists for a very long time. And with a high probability it will have something to do with regulation.

– Is there a well-known arsenal of tools available to bacteria?

– Biochemist Andrey Osterman explained that everything that multicellular bacteria can do, they can also do. That is, any metabolic pathway that you find in multicellular, most likely, you will find in bacteria. It is known from comparative studies that there are several hundred genes that are almost universal.

– Is the ability of bacteria to exchange genes and, accordingly, metabolic pathways absolute or predictably limited?

– She's unpredictable. Moreover, in the history of any gene family, horizontal transfer events have occurred. Bacteria change even proteins that are involved in basic processes. And there are genes that are horizontally transferred en masse. This is something that we are interested in because these are genes that are associated quite often, for example, with drug resistance. And it is useful to understand how the horizontal transfer of drug resistance systems works.

These systems do not arise together with the appearance of new antibiotics, because we do not create them – we take antibiotics from wildlife. There are chemical variants to which bacteria adapt quickly. But initially, antibiotic resistance systems existed long before antibiotics entered medical practice, because it was a chemical war between bacteria.

And these systems are transmitted quite quickly between different bacteria. And moreover, if we made a new antibiotic, that is, we took some kind of natural antibiotic and modified it so that the old systems of resistance to it stop working in bacteria, one of them will learn to resist antibiotics, and this modification spreads with instant speed through the population, and not only through the population, but and between bacteria of different species, too. We can't learn to predict it yet.

– Do bacteria have any adaptation that facilitates this process?

– There is. Many bacteria, such as Streptococcus pneumoniae, have a competence system. When these bacteria feel bad, they begin to ingest DNA from the environment. It is clear that all the time there are some pieces and fragments of those who died, and, in particular, large fragments of DNA. And pneumococci are able to eat a whole large fragment of DNA in order to try to insert it into their genome and see if there is something there that will give some kind of evolutionary advantage. This is a system that facilitates horizontal transfer. And it is known because it was shown on pneumococci that DNA is the carrier of genetic information.

– But it's not profitable either? When you feel good, you won't put any rubbish in your mouth.

– This is on the one hand. On the other hand, when we talk about bacteria, we understand that there are many of them. And it's good for them that different members of this population try something all the time, because if one person is successful, the species will continue to develop, discover new ecological niches. And in general, the observation is that the ability to rearrange genomes increases dramatically in young pathogens that have recently changed their host. And there may be two reasons. First, this population passes through the bottleneck, and there is less effective selection. An alternative explanation is that they feel bad because of the change of owner: they found themselves in new conditions to which they are not quite adapted. And then the mechanisms of experimenting on one's own genome are turned on in the hope that something more substantial will turn out.

– It turns out that most of the genes that once arose still exist?

– To do this, we need to see if the genomes that existed a couple hundred million years ago have anything miraculous. This is something that we cannot count in principle. For example, we see that when a population passes through a bottleneck, some useful skills that it had are lost along the way.

– Going back to the beginning of our conversation: you said that our ideas about kinship have changed. What did you mean by that?

– About fifteen years ago, they said that bacteria do not have an evolutionary tree, but there are conglomerates of genes that are freely exchanged. There are a lot of horizontal transfers that overwrite this signal, but nevertheless, if you take, build many, many evolutionary trees for different proteins, they will all be different, but they will have some common part. And if you average them, then it is approximately clear which bacteria are more related and which are less. If we talk about multicellular, there are close species can hybridize, but there will still be no wonderful hybrid of palm and turnip. And in this sense, we still understand that a palm tree is a separate plant, and a turnip is a separate one.

And if we talk about animals, there were really wonderful revisions of the kinship system. First, it became clear that mushrooms are closer to animals than to green plants. It became clear that many of the million different algae are completely independent branches. And an important conclusion from this is that multicellularity has arisen many times independently: separately in green plants, separately in animals, separately in fungi.

– Do you believe in the argument about the tsunami, the typhoon that swept through the Boeing cemetery, and in the calculations about how incredible life could be?

– On the one hand, we need spontaneous synthesis of sufficiently long RNA molecules so that they can have a reasonable function. On the other hand, we need simpler and simpler RNAs that can replicate themselves. An RNA molecule that can replicate does not have to be a single one. It can be several molecules that interact with each other. And this is the idea of block evolution. Something very simple may arise, for which these probability estimates are not exorbitant. But in combination, they are already doing something so relatively complex.

This is an excerpt from the interview, you can watch the full version here.

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