Males without male genes
Mice don't need a Y chromosome to produce offspring
Elena Naimark, "Elements"
A group of scientists from the University of Hawaii, working with transgenic mice, obtained offspring from a line that does not have a Y chromosome. Moreover, the males of this line did not have a single gene that contains the Y chromosome, and the offspring from such males turned out to be quite viable and fertile. Instead of Y-chromosome genes, spermatogenesis was controlled by some embedded autosomal and X-chromosomal variants. However, judging by the level of expression of Y- and X-chromosomal alleles, the Y-chromosomal gene works incomparably more efficiently. Scientists emphasize the key role of the amount, dose of regulatory factors necessary for normal spermatogenesis.
Let's go back a few years. A group led by Monika A. Ward from the Institute for Biogenesis Research at the John Burns School of Medicine at the University of Hawaii at Manoa publishes the results of artificial insemination of mice with a defective Y chromosome. The results were impressive: if you remove the large arm of the Y chromosome, leaving only 7 genes, then males are still able to produce normal germ cells that are capable of fertilization and the production of viable offspring (Y. Yamauchi et al., 2009. Live Offspring from Mice Lacking the Y Chromosome Long Arm Gene Complement).
Two years ago, the same group issued a new study: the number of genes needed for normal spermatogenesis can be reduced to just two. These are the Sry and Eif2s3y genes. The first of them is expressed in embryos and ensures the development of testes from the gonads, and the second controls the onset of spermatogenesis, triggering meiosis in the germ cells of the testes. With artificial insemination of eggs with sperm produced in such genetically truncated testes, however, quite normal mice develop from them.
That is, scientists seemed to be leading us to the conclusion that the Y chromosome is generally superfluous.
This is what the human genome printed on paper looks like in the Wellcome Collection Museum in London: a cabinet about twice the height of a man; volumes on the shelves, each several thousand pages of the thinnest tissue paper; on each page there are lines of the sequence of ATGTS nucleotides printed in size 3-4; the last volume is the Y chromosome. There, on all thousands of pages, except for the last few, the letters "n" are printed (visible on the inset), which means "meaningless repetitions". Looking at the endless lines of "nnnnnn...." inevitably, one wonders: why did this strange chromosome survive at all?And here are the new results of the same group: even these two genes in the Y chromosome, it turns out, are not required!
The scientists worked with transgenic mice that had no Y chromosome at all. The mice in this lineage carried either two X chromosomes (these are normal females) or one X chromosome. And the Y-chromosome genes necessary for spermatogenesis – Sry and Eif2s3y – were transferred to autosomes (not sex chromosomes). Males X0 could generate underdeveloped sperm, round in shape and without tails, but which nevertheless were quite suitable for normal fertilization. Such lines turned out to be very convenient for research: it is possible, by manipulating two genes embedded in autosomes, to check their functions and potential capabilities. Take, for example, the Sry gene. Its function is to start a cascade of reactions leading to the formation of testes. But the role of the switch, in principle, can be performed by another gene – and so, according to scientists, this role was transferred to the Sox9 gene, which is the direct target of Sry. In transgenic mice, Sry was removed altogether, activating Sox9 instead.
In mice with genotype X0 and Sox9, testicles with round tailless sperms were formed as a result. The second gene is also, if you think about it, not such an irreplaceable player – it has an Eif2s3x analog on the X chromosome. By adding five more copies of this gene to autosomes in the transgenic line, we obtained males X0. Most of them – 35 out of 48 – had defective testes in which no germ cells were found. But in 13 males, the testicles, although small in size, produced the already known round tailless germ cells. These germ cells turned out to be quite suitable for artificial insemination (see the video with the filmed process of artificial insemination of eggs with round sperm. As a result of the appropriate manipulations, viable mice were born. And they turned out to be able to give offspring themselves: scientists received sons, grandchildren and great-grandchildren in the X0 line and without the Sry and Eif2s3y genes.
The result of artificial insemination of eggs with round immature sperm (Round spermatid injection, ROSI) obtained from males X0-Sox9,Eif2s3x: A – pipette, which will be used to select sperm; B – 6 hours after injection, two nuclei are visible in the egg (short arrows) and the second polar body (arrow); C – fertilized the eggs began dividing, after 24 hours two–cell embryos are visible (the length of the scale segment is 50 microns); D - three generations of males X0-Sox9,Eif2s3x, obtained as a result of artificial insemination by injection of sperm ROSI eggs X0; the first male X0-Sox9,Eif2s3x albino, the remaining generations – with dark fur indicating the maternal genotype X chromosomes. All males do not have a Y chromosome, but autosomal X0-Sox9 and Eif2s3x work. Fig. from additional materials to the discussed article in Science.This means that the lack of functions even of these two genes, recognized as the minimum necessary basis for spermatogenesis, is not an absolute guarantee of infertility.
It would seem that the redundancy of the Y chromosome is indeed confirmed. But scientists pay attention to one important aspect of their research, which was revealed when measuring the expression of the Eif2s3y and Eif2s3x genes in X0 lines. It was found that in X0-Eif2s3x lines, sperm are obtained only with very high expression of Eif2s3x, if 4 copies of this gene are included at once. And the Eif2s3y variant copes with spermatogenesis even in a single copy. It works 5-7 times more efficiently than its X-chromosome counterpart.
So, having in principle a spare X-chromosomal variant, you should not get rid of the Y-chromosomal one in a fever. After all, natural selection has been working for him for millions of years. Scientists emphasize that the X- and Y-variants of alleles together give a finely balanced dosage of the necessary regulatory factors. And to claim that the Y-chromosome is so meaningless, apparently, is not worth it.
Source: Yamauchi et al., Two genes substitute for the mouse Y chromosome for spermatogenesis and reproduction // Science. 2016. V. 351. P. 514–516.
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04.02.2015