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Less is more

In 1999, Professor Maynard Olson, one of the founders of the Human Genome project , proposed the evolutionary hypothesis "Less is more" . It lies in the fact that the most plausible optimization mechanism in evolution is the loss of functional genes. Genes break down, but it contributes to change and moving forward. Together with mutations, new opportunities are born. Some may see this as an ethical contradiction, because sometimes we lose valuable genes. The concept of striving for minimalism in evolution raises questions and is still being discussed.

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This material is a reasoning that everything is relative even in evolution and that it is not necessary to level all mutations with the same comb.

Evolution collects genes


Anabena - cyanobacteria. Sphagnum - moss. Fir is a tree. A rose is a flower. Evolution is inevitable. Also, as man is not a “crown of creation”, the process of evolution does not have an initial plan, idea, script. Changes to living beings occur in the context of changes in the world around them. It is not the strongest that survives, but the fittest, and this fitness is relative. So, with the change of conditions around the dinosaurs die out, they are replaced by brisk animals, covered with wool. Speaking about changes, you should not think only about new acquisitions: functions, organs, abilities. Evolutionary change occurs when there is a difference in reproductive success between individuals with different genotypes. We can easily put ourselves in the shoes of losers. All evolutionarily unsuccessful individuals are equally unhappy. The absence of offspring, death in solitude, and now, the heap of harmful mutations that your mortal body has worn is removed from the gene pool. Surprisingly, it is much harder to imagine the opposite picture. It is not clear which mutations make you "fit." To deal with how to adapt to the natural population and what happened in the recent past (including the human), Maynard Olson offered his vision.
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Ctrl + Alt + Delete: Destruction needed


The main idea of ​​Professor Olson is that from a random event a mutation with a loss of function passes into an evolutionary engine. If the gene mutates, that is, the nucleotide sequence changes randomly, the most likely outcome is a breakdown. In this case, the gene becomes a pseudogen. It is simply turned off and stored in the genome, unless, for some reason, evolution does not remove it entirely. In turn, the loss of gene function becomes a standard evolutionary change in a population that is experiencing a change in environmental conditions, such as light, temperature, salinity, competition for resources, and natural phenomena. If we imagine all these factors in the form of a volumetric figure, where each factor influences the form, then what is happening around the population of living organisms can be illustrated by animating the metamorphosis of this figure: something is constantly changing - cyclically or by chance. In turn, in the gene pool of a population, one of the genes may mutate and lose its function, and this change is already spreading over the entire population. If we agree with this idea, questions will inevitably arise.

First question: what is considered a wild type?


In biology, in particular, in genetics, there is the concept of the wild type, wild type. Wild type is the most common phenotype in a population, a complex of characters (or a combination of frequent phenotypes). That is, there is no clear definition of what exactly should be considered a wild type. On the one hand, the wild-type gene variant is one that “meets the norm”. On the other hand, each non-laboratory animal contains a set of wild-type genes. But, in fact, if there is a sharp change in climate, then the “wild types” will change.

In any case, the “wild type” is a model, an absolute, an abstraction. At the same time, in accordance with the less-is-more hypothesis, the Swiss-knife organism, a multifunctional device in which everything is turned on and working, becomes a wild type. Only such devices could hardly ever have been accidentally constructed at all - simply because they would be ill-adapted to real environmental conditions.

The second question: how many genes can you get rid of?


How can you unceremoniously throw away genes without experiencing dire consequences? It turns out that a massive shutdown of genes is possible, but you have to pay for it. The body loses its flexibility in relation to environmental conditions. The best model to illustrate unnecessary non-functional genes is yeast, Saccharomyces cerevisae .

Yeast is a single-celled fungus (and not some bacteria). Each yeast cell can share in two different ways, break down glucose and breathe air with the release of carbon dioxide. In this case, the yeast genome is 6,000 genes. This is approximately 0.5% of the mammalian genome. Yeast experiments often use gene knock out techniques. It is usually used to identify the function of a gene . The experimenters posed the question differently and found out that the yeast survived even if they have knocked out 85% of the genes. The limit of their range is a sterile Petri dish with a nutrient medium, but you can live.

The third question is: where are the links?


How often can we directly observe such genes in a population? If Professor Olson claims that this event is a routine in evolutionary practice, I would like to see examples. Such genes do exist. When the body is relatively simple, the genes can be re-enabled. In other cases, genes simply remain in DNA as evidence of an evolutionary process. For example, bacteria are rather strange creatures, with the help of them, as if, they tested a variety of biochemical cascades and reactions: they can be fed with oil , and chitin, and cellulose . But they are interesting to us in the context of genes that have lost their function.

The most studied among bacteria is for some reason E. coli, the famous E. coli. So, most of the "wild" E. coli carries hidden genes. These genes encode enzymes for digesting carbohydrates that are difficult to break down, so normally the bacterium feeds on more accessible foods. If you plant these E. coli in a Petri dish and do not give them anything nutritious except for “complex carbohydrates,” you can get mutants that will turn on “forgotten” genes and be able to use what they give as a nutrient medium. That is, the function of the gene will be restored . Evolution is not limited to bacteria. Such processes occur in people. The pseudogenes found in humans even proannotized , that is, they described what function they could have. This study was conducted by comparing human genes and their structure with chimpanzee genes.

Fourth question: how to evolve?


How inactivated genes contribute to the subsequent evolution of the organism? Sometimes the function acquired in the process of evolution was redundant, and “gently” adjusting the process that it controls is difficult. Then the advantage is given to individuals whose gene is turned off altogether, broken. And the pendulum swings again.

Armed with a list of human pseudogenes, the scientists decided to analyze their functions. To do this, they chose the Mbl-1 gene, a person in the genome has two copies of the Mbl-1 pseudogene, and there is a line of mice that are knocked out for this gene. MBL protein is a key element in the host's “first line of defense” against infectious agents, such as Staphylococcus aureus. In general, mice, for which, for some reason, Mbl-1 does not work, are characterized by increased susceptibility to microbes, viruses, fungi, but they suffer less from ischemia. Too strong immunity is also dangerous, especially for the person himself. The authors hypothesis is that, perhaps, the conversion of both copies into pseudogenes was more important for people than intolerance towards bacteria.

Fifth question: how does something new appear if we just break the old?
Sometimes breaking is building. The idea behind “Less is more” is counterintuitive. Usually "in order to buy something unnecessary, you must first sell something unnecessary." Anyway, how can you get something new, breaking the old.

First, getting rid of unnecessary things you can dwell in the environment where you could not live before. Loss of pigmentation is important for the inhabitants of dark places: a bright or opaque body makes them vulnerable. However, if you look at our population now, then “gene breakdowns” are more successful from the point of view of reproduction of human beings. Some allow you to maintain low pressure in a diet high in salt or not to gain weight, eating high-calorie foods, and someone has less anxiety during stress. Probably, some of these phenotypes can be associated with loss of gene function (converting fats into digestible form or responsible for the perception of the neurotransmitter). It’s impossible to guess for sure who the “winner” will be. You can learn your strengths and weaknesses, and depending on this build a strategy.

Secondly, with the loss of function, the inevitable can be avoided. CCR5 - CC chemokine receptor 5, a receptor whose role in the immune response is not completely clear. Apparently, he is involved in the inflammatory response. People who have a deletion of 32 nucleotides (the loss of a specific fragment of the sequence) in two variants of the CCR5 gene are immune to HIV . The virus cannot interact with the protein and is not embedded in the DNA, what exactly is happening is shown in the picture. At the same time, it cannot be said that this mutation is common in our population. The AIDS virus has recently become a pressing factor in our environment. You can find out what type of people you are. People with a "healing deletion" can be donors for allogeneic stem cell transplantation to the sick. This means that if the histocompatibility complexes coincide (the same condition is required for hematopoietic cell transplantation in oncology), stem cells that are immune to the virus can be introduced into the human body.

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Last question: Doctor, am I evolving?


Some mutations complicate the lives of their owners. Does this lead to evolutionary success? One example where less is less: you and I, bats, guinea pigs and sparrows have an acute need for vitamin C. Sometime our ancestors (not our common ancestors, but the ancestors of each of the groups separately) went on a diet rich in vitamin C, and we have lost the ability to synthesize it on our own. Now we need to constantly consume vitamin C containing foods for food, otherwise severe fatigue, depression and scurvy may develop. Moreover, different people have different needs for vitamin C, it is also genetically determined. Replacing a gene in a specific region slows down the transport of ascorbic acid and increases its circulation time in the plasma.

Universal living transforming organism is a product of fantasy. At the same time, an overly positive view of things with the idea that “every imperfection is a hidden virtue” is also not true. Truth eludes and environmental conditions change. Mutations occur and are corrected by conservative typewriters in our cells. But not all.

As you already understood, trying on the damage in the genome on yourself is still a pleasure. An individual has no time on an evolutionary scale; moreover, he carries his unique set of imperfections. We cannot predict what qualities will be needed for survival in the future, but you can learn how to eat better in the present in order to make your life more pleasant. In any case, if you are wondering what role your metabolic features play in evolution from the point of view of Maynard Olson, you can check this in Genotek .

Source: https://habr.com/ru/post/399493/


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