How a virus makes a boy out of a girl (2)

Alexey Aleksenko, "Snob"

(see the end, the beginning here)

Chapter Four: Last Summer

If there is a first-class biology, and a second-class biology, and a third-class biology, then the Yale University School of Medicine, of course, nests the highest grade of biology. It is there, in the Stem Cell Center, that the doctor (that is, the professor) works Andrew Xiao. He has a lot of friends there, also doctors and, as a rule, also with Chinese surnames. Professor Xiao and his friends were terribly intrigued by the story of mice-dads, who are born mostly little boys (see chapter three). If you remember, the whole problem with these dad mice is that they don't have an Alkbh1 machine that demethylates the letter A in the DNA alphabet. Professor Xiao thought that since the absence of this typewriter so dramatically changes the family life of mice, it means that they need a typewriter. And, most likely, it is needed just to remove the methyl label from the letter A.

However, no one has ever seen such a mark on the letter A in mammals before. So what? Surely it is there, just not in adult mice, but at some stage of early embryonic development, Xiao thought. And since the professor had biology of the highest grade at his disposal, he decided to look for the marked letter A in the mouse embryo.

And, imagine, I found it (I will not torment readers with a story about how subtle and refined an experimental technique it was). And here our friends-transposons, the LINE1 element, of which there are so many on the mammalian X chromosomes, return to our story. Because the labeled letters A – let me call them N6mA in a normal way, it reads like "en-six-methyl-adenine" - just showed up where there were a lot of these same LINE1 elements.

Or rather, like this: there were few N6mA transposons on the old decomposed corpses. But those that were inserted into mouse DNA a million and a half years ago or earlier had a decent number of them, and the younger and more active LINE1 was, the more damaged letters there were in it.

And what was that letter doing there? And that's what everyone thought: it interfered with the work of the transposon genes. That is, I inactivated him so that he wouldn't jump. And at the same time, the labeled letter N6mA interfered with the work of all other genes nearby. All this, I repeat, occurs mainly on the mouse X chromosome. The one that mutant mouse dads for some reason could not pass on to their daughters. Well, now it's clear for what reason: they didn't have a typewriter to strip unnecessary methyles from the chromosome, turning N6mA into an ordinary letter A.

Dr. Andrew Xiao cooked all these LINE1 and N6mA in his head for so long that a huge pile of his own data and other people's hypotheses somehow merged into one shining image. Namely: as the late Mary Lyon suggested (see the second chapter), the transposon – aka the "ancient virus" – LINE1 plays an important role in the life of the mammalian X chromosome. And not only in girls, in whom he may be in charge of inactivating the extra X chromosome, because girls have two of them. But also boys. Obviously, in the embryonic development of these very boys, it is very important that the labeled letters A (N6mA) are not too few and not too many. If there are too few of them, the elements of LINE1, for good, will start jumping from place to place, causing instability of the genome (from this, by the way, at least there are cancerous tumors). And if there are too many of them, the genes of LINE1 themselves and all the surrounding genes will be completely silenced. And it turns out that this is contraindicated for them – at least, for the maturation of sperm, obviously, the X chromosome, which is too muffled by methyls, is not suitable. The job of the Alkbh1 typewriter is to maintain a delicate balance. The mouse's typewriter broke down – and his X chromosome does not work correctly, becomes defective, and there are no girls in his offspring, but only boys, and even those are kind of creepy.

So it turns out that the transposon (aka the "ancient virus") LINE1 turned out to be very rigidly inscribed in the picture of our entire life, from embryonic development to the moment when our sperm will go on the road to give birth to a new generation of mammals.

Embracing this whole picture with his mind, Dr. Xiao yi wrote his article in Nature last summer (Wu et al., DNA methylation on N6-adenine in mammalian embryonic stem cells). At the end of March, the article was published. That's when the story took a strange turn.

Chapter five. Right now

We don't know exactly what happened there: either the popularizers for some reason became interested in a complex and rather special article by Yale friends with Chinese surnames, or Xiao himself told the popularizers that he had discovered something important, or they were set on him by the university authorities greedy for fame and money. When you look for a solution to a problem for a long time, and then you find it, it always seems to you that the solution is very simple and very global. And now you will explain it to the whole world in just one phrase.

The professor told reporters from his own university bulletin everything at once (Sex of a baby? Ancient virus makes the call). And about the fact that LINE1 is the remains of an ancient virus. And about the fact that these "ancient viruses" are related both to cancer and to the work of the brain (and they really do, and for sure the professor wrote about it dozens of times to different funds, demanding money for his research). And about Mary Lyon's hypothesis. And about the fact that thanks to the demethylase machine, girls and boys are born equally, and if there is no machine, then there are twice, three times, or even four times more boys (journalists managed to record only "twice").

If scientists are banned from vanity, we won't have any science at all, so we won't talk about it. But, of course, the journalists got the impression that literally everything, from retrotransposons to Barr corpuscles in female mammalian somatic cells, Professor Xiao himself had just discovered.

And most of all they liked about the "ancient virus" and about the fact that the sex of the mice somehow depends on all this, so incomprehensible. It was this material that went into the production of headlines.

Of course, journalists also need to understand: it is very difficult to read an article in Nature (yes, try it yourself!) And their duty is to interest the public in science. That is, it is necessary to vividly and briefly tell the public the most stunning of what the journalists themselves have just learned.

And unfortunately, they learned too much for themselves at once.

Then other journalists copied it from them. And then Russian journalists translated it into their own language: for example, here and here.

Some of our compatriots, honor and praise to them, nevertheless turned to the original article. Respect for the foreign-language press did not allow them to say directly that it was all some kind of mud, but they still gently noted the speculative nature of the hypothesis and the fact that the article itself does not contain a word of all the frivolous foam that went into making the duck. And that a new type of DNA methylation in mammals – this very N6mA – is quite a serious discovery in itself, and there was nothing to muddy the water. It is this article by Alexander Ershov that I recommend reading to those who are interested in what was actually done there and how exciting it is.

Because we didn't set ourselves such a goal at all. We wanted to dispel the murk of misunderstandings among readers and at the same time gently scold colleagues. Let's read the primary sources already. Then you yourself complain that we don't have a good science pop in our country. Well, this is not at all because we have small salaries. That's it, sorry, just the opposite.

Elena Gelfand, by the way, asks you the same thing. She, however, thinks that the solution to the problem is a literal translation of English–language primary sources. The example we have considered shows that this is not a solution at all. The solution, in fact, is to read more and not be lazy, that's how banal it is.

Note. I ask enlightened readers to forgive me both the term "transposon" in relation to LINE1, and "typewriter", and "label", and "letter A". You would try to express yourself in a human way. No one would understand you, and even write in social networks that as scientists you are complete shit. And that's a shame. So we try to ingratiate ourselves with the audience, due to weakness of character.

Portal "Eternal youth" http://vechnayamolodost.ru  11.04.2016