2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Israeli scientists have found a way to change the proportion of females and males in the droppings of mammals. To do this, it is necessary to cross a female and a male of two different modified lines: the CRISPR-Cas9 system is assembled in their offspring, selectively attacking certain genes, as a result of which all its carriers die before birth. The scientific article was published in the EMBO Reports journal.
In many vertebrates, individuals of different sex differ markedly in the characteristics of their vital activity. For agriculture, this is often critical: only females provide milk and eggs. Males in this case are needed only for reproduction, but then one individual is enough for several tens or even hundreds of females. Since the sex ratio in the offspring is initially close to 1: 1, farmers get rid of most of the males by simply killing them shortly after birth.
Researchers at Tel Aviv University, led by Udi Qimron and Motti Gerlic, have developed a more humane way to manage the sex ratio in mammalian offspring. It does not prevent the formation of male embryos, but it introduces lethal changes in their genome. Scientists crossed eight male mice, whose Y chromosome carries genes for guide RNA, and females, in which the Cas9 protein gene is inserted into chromosomes from the sixth pair. Together, these components make up the CRISPR-Cas9 system.
In the described experiments, guide RNAs targeted three genes for Cas9 attack: Atp5b, Cdc20, and Casp8. Their correct operation is important at the earliest stages of embryonic development. In a series of control experiments, six males with genes of the same guide RNAs were crossed with ordinary females of the B6J line, which do not have the Cas9 gene (therefore, CRISPR-Cas9 did not work in their offspring). In both cases, the sex ratio of the offspring was assessed.
Eight pairs of modified males and females gave birth to 31 mice, but eight of them died in the first 72 hours after birth. After that, the ratio of males to females in the offspring was 3:20 (they all lived to be weaned from their mothers, that is, they were healthy). As a result of six control crosses, 41 mice were born, of which four died in the first three days. Here the proportion of males turned out to be higher: 23:14. The authors note that this is the first time that in mammals the percentage of representatives of one or another sex has been significantly changed by genetic methods.
Mice crossing scheme. Males carry genes on the Y chromosome that encode guide RNA (gRNA). Females carry on the nonsexual chromosomes (the sixth pair) the gene encoding the Cas9 protein. A complete CRISPR system is assembled in the male offspring of this pair, and it damages a number of genes necessary for the correct development of the embryo in the early stages. Therefore, males die before birth (bottom left), and females remain alive.
Although in the work the sex ratio in the offspring was shifted towards the predominance of females, the authors note that it is possible to do the opposite: to keep only males alive. This may be necessary in beef cattle breeding, since bulls are larger than cows and in this case it may be more profitable to keep them.
Schemes of hypothetical crossing, due to which there will be only males in the offspring of mammals (a), and in the offspring of birds - only females (b) or only males (c)
However, even now it is possible to regulate the ratio of males and females in the offspring, without resorting to the destruction of the "unnecessary" sex. In at least some species of hamsters, the sperm that carry the Y chromosome have smaller nuclei, probably because it is shorter than the X chromosome and requires less space. Thus, it is possible to sort male germ cells according to the size of their nuclei and fertilize females with those cells that guarantee the production of offspring of the desired sex.
