The evolutionary role of tumors
Within the framework of a joint post-science project and St. Petersburg Polytechnic University We are publishing a lecture by Andrei Kozlov, Doctor of Biological Sciences, dedicated to the study of evolutionarily new genes of cancer tumors.
The oncological problem is one of the main health problems, because a very large percentage of people still die from cancer. In addition, cancer patients experience very severe torment. Modern science manages to do something, somehow help, some types of cancer even manage to cure. But the overall picture is that we are not winning this battle.
In the late 1960s, Nixon announced a program to combat cancer (so in the text - VM), after they flew to the moon. It was necessary to fill this vacuum of aspirations, so the United States announced a so-called viral cancer program. As a result of this program, the first viruses that cause leukemia in humans were identified. If we, the human civilization, had not done this, we would not have detected the AIDS virus, because it turned out that the AIDS virus is related to the leukemia virus. And all those technologies that were developed during the study of the leukemia virus during this decade, during the 1970s, were then applied to HIV. Now, recently, Obama announced another, so to speak, fight against cancer, with oncology, because the task has not been completed, which characterizes the problem.
Now let's go from the other side. Why is the problem not solved, because huge amounts of money are spent on it, but nothing happens? Previously, there was such an idea that we need to find a "golden bullet" that will solve all our problems. But it does not work, there is no "golden bullet". Among oncologists, the idea is maturing that, apparently, the tumor cannot be defeated, so we must somehow try to live with it, that is, bring the tumor into a controlled chronic state. All this indicates that it is necessary to work not only on specifics – on specific medicines and some technologies, but also on a paradigm, a general view. It turns out that this kind of need stimulates our thinking, that is, what I will tell you next comes to mind by itself, but it turns out to be in demand because the previous paradigms do not work.
Now I'm going to talk about the evolutionary role of the tumor, which in itself seems a little strange – the evolutionary role of the tumor, the role of the tumor in progressive evolution. If we start to figure it out, it won't be very strange. Firstly, most tumors do not kill the body. After all, we are used to hearing about malignant tumors from which people die. It turns out that both humans and animals also have benign tumors, other types of tumors that do not kill the body. There are more than 50% of them. Such tumors exist, and they can be involved in biological processes. In addition, there is a whole category of inherited tumors that can take part in evolution.
Comparative oncology has been studied for two hundred years. These are tumors in various representatives of the living world – mostly animals, of course, but plants also have tumors. It turns out that no matter what they study, they find tumors everywhere, and it feels like tumors are spread throughout the phylogenetic tree. If they are so widespread, then the question arises: what place do they occupy in evolution?
There is a maxim formulated by the famous Russian-born geneticist Dovzhansky: "Nothing in biology makes sense except in the light of evolution." Therefore, if there is such a widespread phenomenon as tumors, then they should also be considered in the light of evolution. I explain that it's not wild at all, it's not a whim. Many directors work with classics only in order to emphasize some of their own peculiarity. The creation of a theory of the evolutionary role of a tumor is not a whim, but a consequence of the biological way of thinking.
The next group of arguments in favor of the evolutionary role of tumors is that oncogenes and gene-tumor suppressors that control tumors are also widespread. It turns out that they are very ancient, almost the most ancient genes in humans and other animals. It turns out that cellular oncogenes and gene-tumor suppressors are also very ancient, almost the oldest after the genes of "housekeeping" in animals. Another very interesting fact is called the convergence of signaling pathways of development and oncogenesis. What is it? It turns out that some oncogenes play a role in normal development, and signaling pathways of normal development play a role in oncogenesis. Then the question arises: is the tumor part of development?
Recently I showed one slide, a bit encrypted, like the one given to students at the histology exam, with the question: "What is this?" It shows a certain structure similar to a fungus, and there are possible answers. Doctor of Medical Sciences Zabezhinsky, my friend and a well-known morphologist, qualified this as a papilloma. Attention, the correct answer: these are the rudiments of horns in the ancestral beetles Onthophagus. Do you realize how interesting this is? Many developmental processes resemble tumor processes, and both tumors and horns in beetles are regulated by the same insulin-dependent signaling pathway. And then where is the boundary between these processes?
Based on this, I formulated a hypothesis for the first time in the world (and that's why everyone is so sensitive about it now), which suggests that tumors can really play a role in the evolution of organisms by providing excess cell masses for the expression of evolutionarily new genes. Moreover, there are the words "excess cell masses" and "evolutionarily new genes". All of this can be measured, especially evolutionarily new genes. I will now tell you how we measured.
First, before measuring, we found several examples, already described as paradoxical, when tumors really played a role in evolution. These include, for example, the nodules of leguminous plants (this is a plant example, but nevertheless). Nitrogen fixation takes place in the nodules, which resemble tumors, so they have turned into new organs in legumes.
On the other hand, many voles have macrovilli in their stomach, which arise on the basis of malignant papillomatosis and kill these voles. However, they manage to leave offspring. And in other burrowing rodents, on the basis of these malignant villi, benign macro-villi appeared, playing a role in symbiogenesis with some bacteria that help to ferment cellulose.
The next example of this kind is the placenta, which has occurred several times in the history of placentals. As a result of independent infection with various retroviruses that became endogenous retroviruses, the genes of endogenous retroviruses participated in the development of the placenta. And the placenta, which is an organ, has a number of tumor signs (I counted about 12). The most striking tumor signs of the placenta are invasiveness and metastasis, that is, it is a normal organ that behaves like a tumor, and people studying the placenta ask the question: "How does the placenta differ from the tumor?" It turns out, regulation, that is, the placenta is so well regulated that it differs from the tumor. But if it is taken out of control, it becomes malignant.
Why do we need new hypotheses, new theories? They must somehow explain what is happening, what surrounds us, and they must predict. In addition to explaining something with our theory, explaining all the paradoxes that I just told you about, we also predicted something. We have formulated two very non-trivial predictions. The first of them is that tumors can be selected for function in the body. The second prediction is that evolutionarily new genes are activated and begin to work in tumors.
To prove the first prediction, we worked with goldfish. One of them is still alive and is a symbol. She has a beautiful hat on her head, these are lionheads, orandas – they have such cute formations on their heads, in fact, that's why they were selected. When I saw them, I immediately understood what they were: it's a tumor. We did a histology, and, indeed, it looks like a benign tumor. To finally prove this, we conducted a two-year experiment: we looked at the development of a hundred fish, traced all the stages of development of this tumor and made an unequivocal conclusion that the cap of a goldfish is a benign tumor. Then it turns out that breeders have been selecting fish for a benign tumor for fifteen hundred years. Since artificial selection with a benign tumor is possible, in the same way natural selection can work in nature with different types of tumors. This is a very non-trivial result.
We obtained another group of results when proving the existence of genes with double specificity, evolutionarily new, expressed in tumors. When working with evolutionarily new genes, we studied the specificity of their expression. In genes that are known to be expressed in tumors, we determined the evolutionary novelty. We showed in both cases that, indeed, there is a large group of genes, which we called evolutionarily new, expressed in tumors, in English HSEER (Human Specifically Expressed Evolution Removal). In our recent work, we have shown that not only single genes (we have described about 12 of them), but also whole classes of genes can be evolutionarily new. Many of them occur mainly in humans, that is, these are evolutionarily new human genes that have almost one hundred percent specificity of expression in the tumor.
About the author:
Andrey Kozlov – Doctor of Biological Sciences, Professor, Head of the Research Laboratory "Molecular Virology and Oncology" of Peter the Great SPbPU.
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16.06.2016