The five-day embryo (blastocyst) rights. At this stage, well-read by aneuploid errors resulting from improper chromosome segregation during mitosis. To study the effects of aneuploidy researchers used a three-and five-day blastocyst. Photo from bag.admin.ch
US experts to investigate the causes of aneuploidy in human embryos. It is known that aneuploidy – non-multiple number of chromosomes or their parts – causes rapid destruction of embryos and early miscarriage is the main cause of reduced fertility in women. As it turned out, aneuploidy is associated with a specific polymorphism in a specific area on the fourth chromosome. This polymorphism is associated with a gene topographically PLK4, responsible for chromosome segregation during mitosis. It is surprising, but the option PLK4, causing reduced fertility, is widespread in the human population, its rate is quite high. Scientists are discussing the question of how could seemingly harmful gene spread in the population, and not drop out selection.
Experts from Stanford University and the company’s genotyping Natera dismantled interesting case of fixing harmful trait in human populations. “Harmful” – means reducing reproductive success. In this case, reduced reproductive success was not a remote consequence of a harmful trait, such as low resistance to disease or gender unattractiveness, and a direct result of reducing the quality and survival of embryos. Scientists interested in the number of defective chromosomal regions – so-called aneuploidy cases when part of a chromosome (or an entire chromosome) or is lost or present in duplicate. Such errors occur during meiosis or mitosis when proper chromosome segregation violated the daughter cells. It is known that aneuploidy causes the death of the embryo in the early stages of development and miscarriages. In their study, the researchers assessed the level of aneuploidy in eggs and early embryos and found out what has caused the emergence of such errors.
Much of the effort was spent on finding out the time of occurrence of aneuploid errors. Clearly, they can appear as in meiosis as in mitosis. In the first case aneuploid chromosomes will be found in the unfertilized egg, the second – in early embryos. Experts worked with samples of artificial insemination: eggs, sperm and early embryos at the blastocyst stage. When the art PCR was possible to read the genomes of parental cells and embryos. This material – it should be noted, quite massive – allowed to estimate the proportion of aneuploid and other types of errors. The reasoning was approximately as follows: since the errors in aneuploid sperm during meiosis extremely rare (as it is known), all the errors in the paternal genome of the embryo can be attributed to mitotic abnormalities.
Mitosis in the early stages of embryonic development is regulated by maternal genes, so it’s possible that an error chromosomes are responsible or that maternal genes. Having data on maternal genome, you can look for these unfortunate genes. To do this it was necessary to compare genomes of nuclei which have appeared in aneuploid errors, with those where no error occurred. And thus revealed a plot for the fourth chromosome variations which correlate maternal with aneuploidy embryos. Features of this site indicates that it is under strong influence of dynamic selection: there are signs of the so-called “sweeping through the selection of polymorphism” (see .: Selective sweep). One of the genes located in this area, – Polo-like Kinase 4 (PLK4) – has been well studied, and its function is related to the regulation of mitotic spindle formation and, consequently, the differences of paired chromosomes into the daughter cells. This gene Doctors excellent candidate for the role of the offender that order.
Check the available databases and private data collected by scientists showed that the “harmful” (increases the likelihood of aneuploidy in embryos) version of this piece of DNA is extremely common in a variety of human populations (with a frequency of 20% to 45%). All peoples have this genetic variant. It is interesting to note that it is not found neither Neanderthal nor denisovtsev.
It turns out that the genetic embryonic aneuploidy – the property is clearly unprofitable for reproductive success – in fact spread quite widely in the human population. It appeared, presumably, after the separation line and was supported sapiens selection. On average, people have only 30% of conceptions leading to successful pregnancy, and most of the failures are due to aneuploidy.
Why selection favored the spread of the harmful trait? Speaking about this, the scientists put forward a number of hypotheses. The first sign may be harmful, but it turned out to be linked to another feature, the benefits of which exceeds the harm of aneuploidy. Second, the harm from reduced fertility, probably not so great for the human population.
Scientists offer a version of balancing selection. They are based on the fact that the frequency of this allele is more or less similar in all human populations. This means that in this case, triggered some kind of common patterns. For example, scientists believe, reduce the likelihood of pregnancy, as well as concealed ovulation and constant readiness of females to mate, it led to the fact that males were more difficult to determine who is the father of the offspring, and therefore more males to invest in taking care of it. But, unlike the hidden ovulation and constant readiness for sex, this feature is still a negative impact on reproductive success. Therefore, it does not fully entrenched, it balances and fills allele does not cause aneuploid disorders. Women with enhanced ability to reproduce, thus enjoy the benefits sought by mothers with low probability of pregnancy.
It should be noted that such a scenario is balancing selection – only one possible, and American experts do not insist on it. Anyone can come up with a scenario for balancing selection. For example, it can be assumed, and this: a mother who rarely bear and give birth to children, keep better health and, therefore, have more options and power to take care of the offspring – as his and his sisters, and even grandchildren. After all, the health of the woman, the more likely that she will see her grandchildren and help them to grow – who doubt the benefits of grandmothers!