How a virus makes a boy out of a girl (1)
The story of a popular science duck, born through the joint efforts of popularizing journalists from different countries
Alexey Aleksenko, "Snob"
"It's a girl! Ancient viral genes can determine the sex of a child," says the title of the article on the venerable English–language resource. In the Russian translation, everything turned out to be even tougher: "An ancient virus determines the sex of a child." The author of this article decided to go a little further along this path (see the title). But in fact, this is not true. Viruses don't do anything like that. And in general, this is not a story about gender or viruses, but about how popularizers (like yours truly), saving their precious time, instead of knowledge spread ignorant obscurantism and turned a fascinating story of scientific research into shameful clowning.
And this story began about ten years ago. No, in fact, it began about a billion years ago, so it will be more accurate. And in order not to confuse the reader even more, we will tell it in parts. No rush this time.
Chapter one. Billions of years ago
A very, very long time ago, our ancestors were attacked by parasites. It's hard to say what our ancestors looked like then, but they were almost certainly unicellular. And the parasites seemed to look exactly like the current viruses. For example, some of them have already mastered the trick that the herpes virus or the much more unpleasant human immunodeficiency virus (HIV) demonstrate these days: they were embedded in the genome of the cell (I remind you: our ancestor!) and they lurked in it for as long as they wanted, doubling along with the chromosomes. And then how they pop out!
But some never popped out. Firstly, the most pragmatic viruses at some point realized that there was no need to arrange this whole farce with epidemics: you can also have fun just by staying embedded in the chromosome and multiplying with the host. Well, except sometimes jumping from place to place. Such sensible viruses no longer need any proteins from which a viral particle will be built: a simple machine that will make copies of DNA and then insert them into other places is enough. Over time, they became so unlike viruses that they were called differently: transposons.
Secondly, our ancestor was also not so simple, which we know at least because his descendants have lived to this day, and we are among them. He learned to deal with the virus pretty quickly, even if it was embedded in a chromosome and disguised as a normal gene. Our ancestor came up with the idea that it is necessary to slightly spoil the viral DNA. The simplest and historically proven way is to hang chemical labels on it, methyl. Then the viral genes corrupted by methyl will no longer be able to work: that is, not only mature virus particles will not form, but even stupidly jumping from place to place will no longer work.
Such viruses (and transposons) have remained alive in our chromosomes forever. Enough of them have accumulated over a billion years: they say 40% of our genome is the remains of viruses and transposons at different stages of decomposition. But no, no, and a new transposon will come from somewhere. And then the body again needs to control its behavior by hanging molecular labels on it so that it does not become too active and does not interfere with cells to live normally.
Gradually, a balance was developed between the interests of the transposon and the host: the host controls the transposon (including by methylation), reducing its activity, but from time to time the transposon is still delayed and jumps to another place. If you do not abuse such jumps, it will not hurt the owner, but it is not in the transposon interests to ruin your only owner at all. There was also a benefit for the host: transposons, jumping from place to place, ensured the mobility of the entire genome – a useful thing if you need to somehow evolve.
So, as a result, after a billion years, our genome turned out to be chock-full of transposons. And not only ours: mice, rabbits, fish, and fruit flies have plenty of them. One of them is called LINE1. For some reason, there are especially many of them on the sex chromosomes. That is, on the X and Y chromosomes – those that determine the sex of the child.
Chapter Two: Hundreds of millions of years ago
Then this happened: our ancestors had a mechanism for determining the sex of the embryo. How exactly it turned out is another question; perhaps it all started the way we told here in one note about birds. But in the end, the situation is as follows: all chromosomes are paired, and one is not quite. In girls, it is still paired, called X, and they are present in all eggs. And the boy has one X – a big, fat, perfectly normal chromosome with genes and all the accessories. And the other Y is small, almost without genes. Boys' spermatozoa carry either X or Y, and if Y gets to the egg, X will already be waiting for her there, and a boy will be born. And if X gets there, then two X will turn out, and a girl will be born.
But the girl has a problem: the genes that sit on the X chromosome will be exactly twice as many as the boy. This is bad, sloppy. Therefore, one of the girls' X chromosomes must somehow be cleaned out of sight, deprived of power. And our ancestor had long been able to deprive unnecessary genes of their power: by that time, he had already inactivated transposons for a long time.
English geneticist Mary Lyon (Mary F. Lyon), who lived on Earth for 90 years and left this world two years ago, suggested – and not without reason – this is what. We eukaryotes are perfectly able to neutralize the pieces of the chromosome, where one after another, like repeating links in a chain, the bodies of once active viruses, or transposons, are stacked. It is quite logical that when our ancestors had this whole kitchen with two different sex chromosomes, and one of them had to be somehow silenced, they simply used a long-tried method. Fortunately, this very X chromosome already largely consists of the aforementioned LINE1 stacked one after the other. You see, from the point of view of smart modern biologists, LINE1 is an alien and an alien. And from the point of view of our stupid but experienced ancestor, everything was just the opposite: transposons were a long-standing and familiar accessory, but the problem with different chromosomes in boys and girls that had just arisen had to be solved from scratch. Well, our ancestor took advantage of what he had: he just adjusted the car a little, which has already proven itself perfectly in solving other tasks. There is a repeating series of transposons, and we will roll them into a compact ball so that their jumping genes do not interfere with our lives. There is an extra chromosome – well, we will roll it up in the same manner, the benefit of these transposons on it is like mushrooms behind a bath.
Here's what happens: on the basis of viruses that were once parasites, our ancestors made a very necessary thing in everyday life - since they could not get rid of them at the time.
Chapter Three: Ten years ago
Here we will part with our transposon friends for a while and turn to a completely different field of biology. Different organisms have such a protein, the enzyme alkB: it can, for example, remove a methyl label from one of the letters of DNA, namely from the letter A, from adenine. Bacteria have it, where the letter A is indeed often marked with methyl. But mice have it, and you and I have it. Somehow it has always been believed that only the letter C is labeled with methyl. Then why do we need a special machine that removes the label from the letter A?
To understand this, ten years ago, Norwegian researchers bred mice that did not have this alkB machine (however, in mice this thing is called Alkbh1). And six years ago they told about the results. Mice without a typewriter were very strange: they looked sick, ugly, not too prolific. The bones of their skull grew incorrectly, they were often born one-eyed. And most importantly, boys predominated in the offspring. That is, if the mouse dad didn't have a machine for demethylating the letter A, the descendants of such a dad were mostly boys (up to 80%) and looked lousy. And if mom didn't have a typewriter, then everything was OK with the ratio of boys to girls, although the mice were also so-so. An intriguing result, especially if we remember that there seems to be no need to demethylate the letter A at all, since, according to the data of that time, it is never methylated in mammals.
But some assumptions can be made. Since mutant dad mostly gives birth to boys, it means that dad's sperm very rarely carry a normal dad's X chromosome. And if so, then this same Alkbh1 machine is needed in order to somehow prepare Dad's X chromosome for the solemn moment of fertilization. In other words, when a mutant dad's sperm matures, some important ceremony does not occur with the X chromosome, in which, apparently, this very machine-demethylase should participate.
The Norwegian authors hypothesized that this could be a rite, and there is no point in remembering it, because it has not been confirmed. And what actually happened there, it became a little bit clear only now. That is, it became clear to biologists, and it would have become clear to everyone in the world if we, the popularizers, had not spoiled history with our idiotic enthusiasm. But about this – in the next part of our unhurried story.
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11.04.2016