New adventures of the Weismanists-Morganists

This boring article about genetics is designed to permanently discourage the reader from talking about natural selection and other matters inaccessible to him

Alexey Aleksenko, "Snob"

Only the humblest of the ignorant have no opinion about the theory of evolution. The rest express their opinions without hesitation. Recently we had to hear that natural selection could not create a variety of species of living organisms, because selection only kills, which means that there should be fewer species over time. And this is not the biggest nonsense that you have to listen to when it comes to natural selection.

Or here is such a paradox. In order for evolution to move forward, selection must consolidate beneficial mutations and remove harmful ones. Let's say that at some point selection manages to create an organism ideally adapted to its niche. But harmful mutations continue to appear. There are no problems with the most harmful ones: their carriers immediately die. But there are mutations, the harm from which is quite small. Most likely, the first generation of descendants of our ideal organism will retain some share of these mutations. The next generation will add more to them. Then another and another. Regardless of the strength of selection, there will always be mutations with such a small, imperceptible harm that selection will not have time to remove them. As a result, our body will inevitably deteriorate over time. And not to improve at all, as should happen according to Darwin's intuition. So genetics and Darwinism are incompatible.

This reasoning, in its stupid simplicity, can compete with the above maxim about the origin of species. Meanwhile, here it is just right. It took genetics almost a hundred years to get close to solving this paradox. But before we talk about the recent work carried out under the leadership of Alexey Kondrashov, we will have to make a small historical digression.

Historical digression

Genetics, unlike Darwinism, is respected by everyone. This is partly due to the Lysenkoist persecution: when an entire branch of science becomes a victim of tyranny, it becomes as inappropriate to make light jokes about it, as, for example, about the magazine E. M. Albats The New Times. Darwinism was less fortunate: at that time it was raised to the shield by very unsightly forces. This is not surprising: Darwinism really seems so simple at first glance that it does not seem to offend the ignorance of a simple Soviet person offended in childhood by more intelligent classmates. But when such a person is offered to understand why epistasis is characterized by splitting 13:3 in the second generation, it's time to get angry and write a denunciation.

This attitude persisted even after a complete change of ideological polarity: as noted above, at the beginning of the XXI century, it is still believed that any ignoramus can come in from the cold and make judgments about Darwinism, now critical. It will even seem to him that he is succeeding.

A very similar situation, by the way, has developed with the two main halves of physics: those who want to refute Einstein have not been translated for a hundred years, but there are not so many who want to revise quantum mechanics – for this it would first have to be learned, and it is incomprehensible.

An analogy with physics can be found in another aspect: No matter how ridiculous Einstein's refuters are, physicists cannot yet mock them with a pure soul. The trouble is that the theory of relativity is really not consistent with quantum mechanics (although homegrown philosophers will never understand exactly what it is). So genetics with Darwinism still has problems, also unknown to the laymen.

Darwin himself knew nothing about genetics and had no idea where the small inherited changes that serve as material for selection come from. This gap was filled by August Weisman, after whom, in fact, genetics in the USSR was long called "weismanism-Morganism" (the second half of the nickname comes from Thomas Morgan, who connected abstract "genes" with chromosomes visible in a microscope). Weisman started talking about spontaneous mutations and became the founder of a theory that was called "neo-Darwinism". But there were weaknesses in this theory.

One of such weak points is just the paradox described above, which was called the "Meller ratchet" (we already wrote about it a year ago, talking about the charms of sex). A ratchet is a wheel that can rotate only in one direction, because a special tooth prevents it from turning back. That's how the mutation process, it turns out, is able to turn around only in one direction: to worsen everything he undertakes. Sexual reproduction can help here, from time to time mixing all the mutations and accidentally giving out individuals free of harmful cargo. But mathematical models show that this trick works only under special assumptions about the properties of mutations. Which, as luck would have it, may not have such properties, and then the whole evolution goes down the drain.

The War against Mutants

Those mathematical models of the "Meller ratchet" in the conditions of sexual reproduction, which we mentioned, were created several decades ago by a young scientist Alexey Kondrashov. It is difficult (although I really want to) call Alexey a Russian scientist for two reasons. Firstly, his scientific activity has been taking place mainly in the USA for a long time. Secondly, speaking of scientists of such world renown, it is somehow not customary to point out the origin (Stephen Hawking, after all, no one calls a British scientist). Alexey Kondrashov is one of the leading theoretical biologists of our time, and the paradoxes of the mutation process and natural selection are the main topic of his research.

And this topic is becoming more and more acute. When Herman Moeller invented his ratchet, the topic of accumulation of mutations was of purely theoretical interest. When Kondrashov built the first mathematical models in the 1980s, he could make any assumptions about mutations, because they were not so easy to verify. But since then, tens of thousands of genomes have been deciphered, and a grim reality has opened up to the eyes of scientists.

Absolutely every newborn person carries an average of 70 new mutations in his genome. Previously, it was thought that this was not so much, because only one and a half percent of our genome encodes proteins: there is a chance that out of 70 mutations, none will fall into a vital area at all. But now it turns out that at least 10% of the entire human genome is functionally significant. And this means that each newborn carries about seven new mutations that are potentially harmful. Even the most conservative calculation shows that no selection will have time to remove such a mutational load: our species is doomed to perish under it in just a dozen generations. And, by the way, the fruit fly of the fruit fly will also disappear, because it has similar statistics, although it is not as sorry as us.

However, neither we nor the fly have disappeared yet. So, there is some kind of mistake in this whole story with mutations and selection.

Error detected

To understand whether selection will cope with the removal of harmful mutations, geneticists compare the rate of occurrence of mutations with the total selection coefficient. But this trick only works if all these mutations act – and are eliminated by selection – independently of each other. In real life, genes, and therefore mutations, interact – geneticists call it a beautiful word "epistasis".

This is where the very difficulties begin, which the homegrown critics of Darwin do not have the slightest desire to understand. But Kondrashov and his colleagues figured them out.

Mutations can interact, for example, according to the principle of "seven troubles – one answer": if one harmful mutation already exists, selection does not notice the rest. In such a situation, the real selection will be even weaker than calculated according to simplified formulas, that is, humanity – like flies – is doomed.

But mutations can interact, as they say, "synergistically": the harm from two mutations will be stronger than the sum of their individual harms. The total force of selection (for all our 70 mutations) at the same time may be quite sufficient to save humanity from a mutational catastrophe. It is a pity that calculating the selection coefficients for all three billion loci of the human genome, and then also checking ten to the nineteenth degree of interactions between them, is an impossible task.

And here you can cheat: look at the results of the experience already set by nature. After all, if mutations are scattered independently of each other, their number will be distributed randomly between organisms. About the same as the number of mahjong wins between four players who played all night. And if nature – that is, selection – does not like it when there are too many mutations, the distribution will be more strict, as if the luckiest player, ashamed of his luck, started dropping the necessary chips by morning. It remains only to see how the number of mutations is distributed in real cases, whether in humans or in flies. This task is also not easy, but it is quite capable of modern computing power.

The result of Kondrashov and colleagues: the distribution of the number of mutations turned out to be not at all random ("non-Poisson", as these arrogant scientists put it: their variance, you see, is less). And this can be explained in the only way: on average, mutations interact quite strongly with each other throughout the human genome, so one plus one is significantly more than two. And in this case, it is much easier for selection to cope with the purification of the genome from harmful cargo.

Thus, Kondrashov managed to prove the very arbitrary premise on which the famous "Kondrashov hypothesis" about sex and mutations was based: selection cuts off the most mutation-burdened part of the distribution. By the way, this hypothesis entered the history of science as the "Kondrashov axe", which is illustrated by a funny picture.

Saving the human race

So, the human race is saved. At least, its existence ceases to be a ridiculous curiosity from the point of view of scientific Darwinism. However, the existence of those who still intend to refute scientific Darwinism from general ideological premises, without really understanding a damn thing, is still curious.

In conclusion, I probably need to explain something. When the author says "the human race is saved, because selection manages to clear it of mutations," one must understand that he is walking on thin ice. The Social Darwinists proposed to purify the human race with the help of natural selection, and Hitler really took it (as follows from the only phrase in Wikipedia, Hitler only encouraged unhealthy competition of his own subordinates, and in general, artificial selection was practiced in fascist Germany, and many social Darwinists approved of eugenics - VM).

Nowadays, it is already indecent to rejoice that humanity is undergoing regular cleaning by selection. The authors of the article explain what they mean: only 30% of human conception leads to the birth of a child. Of the remaining 70%, the vast majority are spontaneous miscarriages, usually occurring in the early stages of undiagnosed pregnancies. Geneticists believe that their main reason is precisely the mutational load removed by selection. No one says that early miscarriages are good and fun, but there is little fun in nature at all. But she, nature, has arranged everything so that you and I appeared on the scene, and even we are not degenerating under the burden of mutations, but we are developing dynamically. And what's even nicer, biologists have finally figured out how we do it.

Portal "Eternal youth" http://vechnayamolodost.ru  16.05.2017