Sex car?
Sex as Conflict: War in the Womb Various reviewers noted a confusing and complicated structure of the book. Excerpts from the chapter on imprint, chillingly titled - I know what I'm talking about - war in the womb show why this is indeed the case. Sex, at least from an evolutionary perspective, is complicated and confusing. Various reviewers also attested this to the book. Biology students, former biology students and Hessian biology teachers followed the verdict. So here's a little self-portrayal of how complicated the whole thing really is. This is a phenomenon that cannot be reconciled with Mendel's laws. This would not be too tragic, because it is well known that the law of independent distribution does not apply to genes on the same chromosome. This does not diminish confidence in Mendel's laws. The phenomenon of the imprint contradicts all ideas that have been established in the last 100 years. Therefore, Siddhartha Mukherjee sends greetings, various confused representations have been established in the analysis of imprint genes in connection with the inheritance of acquired characteristics. A little advice: Ask your current doctor what kind of organ the placenta is. An organ of the mother, of the unborn child, or a symbiotically functioning one of the two? An excellent account of this can be found in Life's Vital Link - The astonishing role of the placenta (2013) by YW Loke But here are some digestible excerpts from Chapter 4: Sex as Conflict: War in the Womb - Epigenetics and the Genetic Imprint We are all in the caught sex. Never will a woman come along and - as is common with so many other creatures - give birth to a healthy baby from an unfertilized egg. We are trapped in sex, but the male and female genes responsible for it have interests of their own. Sex is a genetic battle between the sexes with far-reaching practical consequences. For example, future romantics should be wary of the illusion that all genes work together in harmony to produce a healthy child. "War in the womb" or "conflicts over the placenta" have been the buzzwords geneticists have been using to describe what happens during pregnancy for some time. About ten years ago, attention was first drawn to the existence of paternal genes in the fetus, which behave in a completely selfish manner and can thus, under certain circumstances, cause serious damage to the health of the future mother. Reik is fascinated by the imprinting phenomenon, other geneticists speak of one of the sensational discoveries of the last 20 years. Because imprinting genes contradicts everything biology students have learned about heredity for 100 years. According to an iron rule of genetics, in species with two sets of chromosomes, one gene – or more precisely: the possible form of a gene, also known as an allele – usually characterizes a trait, regardless of whether it is inherited from the father or mother. The Augustinian Father Gregor Johann Mendel (1822–1884) was the first to recognize this in his groundbreaking experiments, which he carried out in a monastery in Brno: if he crossed short-stemmed peas with long-stemmed peas, he always got the same results: plants with long stems, regardless of whether the gene copy for long stalks came from the ovum or from the pollen. The gene or heredity factor - Mendel spoke of trait - for long stems is dominant over that for short stems. "Paternal genes are greedy and suck valuable nourishment out of the mother-to-be," says Wolf Reik, explaining the situation. Reik has been a researcher at the Babraham Institute in Cambridge, England, in the Department of Developmental Genetics for 19 years. He publishes articles in scientific journals on parental influence on the genome, dramatic conflicts between paternal and maternal genes in the womb, the battle of the sexes that begins in the fertilized egg, the programming and reprogramming of the genome in the early embryo, and importance for cloning. Reprogramming means that a genome is transferred back from an already specialized cell to the state of a totipotent embryonic cell. Surrounded by laboratory mice, DNA sequencing machines and employees from all over the world, Reik's main interest is in the phenomenon of genomic imprinting, which caused only astonishment when he discovered it: the genetic material in the sperm and in the egg cell each has its own pattern that leads to this This means that some genes from the mother's and the father's side in the embryo - which, and this is crucial here, are not located on the sex chromosomes - are expressed differently. A label is attached to each gene that says either Hello, I come from the father, do this or Hello, I come from the mother, do this – although both this and this often stand for opposite information. But both gene copies must be present, otherwise things get critical. Reik is fascinated by the imprinting phenomenon, other geneticists speak of one of the sensational discoveries of the last 20 years. Because imprinting genes contradicts everything biology students have learned about heredity for 100 years. According to an iron rule of genetics, in species with two sets of chromosomes, one gene – or more precisely: the possible form of a gene, also known as an allele – usually characterizes a trait, regardless of whether it is inherited from the father or mother. The Augustinian Father Gregor Johann Mendel (1822–1884) was the first to recognize this in his groundbreaking experiments, which he carried out in a monastery in Brno: if he crossed short-stemmed peas with long-stemmed peas, he always got the same results: plants with long stems, regardless of whether the gene copy for long stalks came from the ovum or from the pollen. The gene or heredity factor - Mendel spoke of trait - for long stems is dominant over that for short stems. So male and female germ cells have equal rights, a finding that was revolutionary at the time, since many researchers and doctors in the 19th century, most of them male, believed that the semen shaped the hereditary disposition. Mendel's findings are by and large still valid today, but for a few genes it does matter whether they are inherited from the mother or the father: in genomic imprinting, the traits that appear depend on whether they are passed on to the oocyte or the sperm enter the zygote; Certain chromosome sections are specifically marked in the male or female germ line - i.e. the cell line from which the germ cells that develop separately from the body cells, the soma, emerge - so that in the body cells of the newborn individual either only the paternal or the maternal copy of a gene is active. A classic example of genomic imprint or imprinting is a gene called Igf-2, which is located on chromosome 7 in mice and encodes the insulin-like growth factor 2 (insulin-like growth factor): Growth factors are proteins that cells use during growth and growth Regulate formation of tissues. The insulin-like growth factors belong to a group of chemical compounds that are produced by the liver and are important for the formation of the skeleton; In general, the interaction of numerous growth factors is responsible for the complicated behavior of cells in developing tissues and organs. In the fetus, the Igf-2 gene drives cell division, while in the placenta it controls the transmission of food from mother to embryo. Remarkably, the gene in the mouse embryo is only active on the paternal copy; it is normally switched off in the maternal copy, as if the paternal genes wanted to get a particularly large amount of food resources from the mother. This sounds strange, and the same can be said of the results of those pioneering experiments by two research teams in Philadelphia and Cambridge, which led in 1984 to consider the existence of an imprinting pattern for the first time. "But actually it all began with the question of parthenogenesis, unisexual reproduction," Reik recalls. “Why in mammals does not a living being develop from the unfertilized egg? This question was left unanswered for years. Now there were a few basic possibilities as to why virgin birth does not occur among us, and one of them was that the genes are sex-specific, that is, that they are imprinted. This would mean that parthenogenetic embryos lack the imprint of the father. But such a mechanism was then only considered as a theoretical possibility. And a second aspect – very important at the time, but perhaps forgotten now – was that there was a man named Illmensee. In the 1970s and early 1980s, Karl Illmensee was considered a child prodigy of embryology: in 1977 he produced mice only paternal or only maternal genes, a little later he even cloned mice. At least those were the findings that Illmensee published. "He was so highly regarded as an embryologist," says Reik, "that many believed that only such a technically brilliant man, who was far ahead of his time, could carry out such spectacular experiments at all." To produce mouse pups from only paternal or only maternal genes , the genetic material of one of the two pronuclei must be exchanged in the zygote, the fertilized egg cell. These pronuclei develop a few hours after fertilization, one from the egg and the other from the sperm that has penetrated the egg. Both pronuclei therefore contain the chromosomes of the male and female parents respectively, so they are still haploid, meaning they only have one set of each chromosome. Bioethics officials from various organizations are happy to announce that the final fusion of the egg and sperm, which results in the creation or conception of new life, takes place in the fertilized egg cell. Well, this statement is true for the sea urchin, but not for mammals: the pronuclei in mice and humans in the zygote get closer and closer, but initially remain separate. Only when these two pronuclei migrate to the center of the cell do their nuclear envelopes, the membranes, begin to interlock. Then the two pronuclei duplicate their chromosomes and the cell prepares for division. But the maternal and paternal chromosome sets remain nicely separated: the final merging of the parental genes only takes place in the two-cell stage. So it should somehow be possible, as cell biologists imagined around 1980, to suck out the DNA from a pronucleus and replace it by injecting it with another DNA. Karl Illmensee now claimed to have implanted a pronucleus with maternal chromosomes in an unfertilized egg or to have removed the female pronucleus from the unfertilized egg and to have replaced it with two pronuclei with sperm chromosomes. Suddenly there were supposedly mouse embryos that, genetically speaking, did not have the usual two parents, but only paternal or only maternal. In addition, Illmensee had claimed that his one-parent embryos had developed into splendid mice. However, no other scientist was able to repeat these experiments. Developmental biology took a crucial turn when cell biologist Davor Saltor in Philadelphia developed a method in 1983 that allowed pronuclei to be exchanged and fused in a much simpler way than had previously been possible. Thanks to this technique, parental embryos could be produced relatively quickly; In 1984, the Philadelphia group and a team in Cambridge led by developmental geneticist Azim Surani published their results. Both came to the conclusion that it was completely impossible to exchange pronuclei in such a way that the embryos - which have a normal number of chromosomes but only a double set from the mother alone or only from the father - can develop normally. These single-parent embryos looked strange and quickly died in the womb. The embryo with the mother-only genes contained relatively well developed embryonic tissue, while the surrounding tissue, which includes the placenta, was scarce. Conversely, the sperm-only embryos: The embryonic cell tissue was underdeveloped, while the experts wondered about a relatively well-developed placenta. However, the conclusions were clear: embryos with only the paternal or only the maternal genome are not viable. Both genomes are needed for normal development. “And the reason for this, it was concluded, is that the chromosomes are marked by imprints, which means that the chromosomes are parentally marked. At least that was the suggestion at the end of these two articles, although no concrete mechanism for such imprinting was known at the time." "And then what about the Illmensee mice?" "Saltor's and Surani's results directly contradicted the result of Illmensee, who yes, allegedly produced a parental mouse," Reik replies. As early as 1983, Illmensee's laboratory at the University of Geneva was examined for these inconsistencies. Although no research botch or even fraud could be proven, the commission raised serious allegations against his record keeping and the way in which he had organized his laboratory. In 1985 Illmensee disappeared from Switzerland and thus from the international research scene, at the same time Reik started looking for a job in England after completing his doctorate in Hamburg. He visited various laboratories in England, including Azim Surani's in Cambridge. "I'd heard from him, not very much, his article had just come out, so the whole thing was still very hot," says Reik. “I was so fascinated by these experiments with single-parental mice that I immediately thought about the possibility of finding out the molecular mechanism for imprinting. Above all, I wanted to find specific genes that are subject to imprinting. So I quickly applied to Cambridge and was accepted. In fact, we found the first DNA methylations back then, and the results were published in Nature in 1987. And it turned out that imprints are parent-specific and based on DNA methylation.” What does DNA methylation mean? How is it that in an embryo, for example, only the paternal copy of a gene pair is active while the maternal copy suddenly becomes silent? The mechanism that causes this imprinting is quite unspectacular and well known from other DNA inactivation processes in a cell: the gene in question is made silent through a process called methylation. In the DNA double helix, a so-called methyl group made of carbon and hydrogen (-CH3) attaches itself to the base cytosine, which modifies the letter C of the genetic alphabet. To be more precise: If a methyl group binds to the cytosine in the activation region of a gene – i.e. where transcription, the transfer of information from DNA to RNA, is initiated, the gene no longer passes on the instructions it contains to the cell; the methylation makes the genes silent; however, there are exceptions where the exact opposite is the case. “Let's focus on the general for now. So the imprinting takes place during the formation of the germ cells?” “Yes,” Reik replies, “but we don't yet know exactly how it works. A methylation imprint is set in one germ line – for example in the immature egg cell, the so-called oocyte, but not in the other germ line, i.e. not during spermatogenesis, the formation of sperm. If fertilization then occurs, the gene is imprinted or methylated on one chromosome and not methylated on the other chromosome. The important thing about this methylation pattern is that it is somatic, i.e. in the body cells, stable: If the chromosomes are duplicated during cell division, the methylation pattern is also replicated, so they are preserved. By replication we mean the exact multiplication of an organism, cell or DNA: so when the cells in the embryo multiply, the difference between the maternal and paternal chromosome remains. This means that one copy is shut down, ie not transcribed, while the non-methylated copy is transcribed. However, the specific factors that trigger these mechanisms are unclear. All we know is that the imprint in the germline involves enzymes that can methylate the DNA." "And is this methylation the reason why only the genes coding for this organ are active in a liver cell and the other genes are silent?” “The scholars argue about that,” Reik replies. 'But that would be the same mechanism that could be considered?' 'That would be a potentially very good mechanism for silencing genes that are not needed. But you don't know. The experiment with which one could really prove this is not easy to carry out.« Reik reports on an experiment in which the methylation in the genome of a mouse is practically 90 percent eliminated. This is technically very difficult, but one can work with embryos in which the enzymes that cause methylation have mutated. These embryos die early, a testament to how important DNA methylation is to a healthy individual. Ultimately, however, all gene activities in the mutated mouse embryos would have changed in such a way that it would be impossible to interpret this experiment exactly. Then Reik begins to talk about a particularly fascinating aspect of genomic imprinting, about how the imprints must always be set correctly in each new generation, regardless of whether they enter the embryo from the mother's or the father's side, regardless , whether in mice, gorillas or humans. For example, there is an imprinted gene that comes from the father; the marking is thus passed on to the offspring via the sperm. The child, let's assume it's a girl, has the muted copy of a gene on the chromosome that comes from the father's side, while the gene copy on the maternal chromosome has not been switched off, i.e. it is active. Although egg formation in the daughter begins with an undifferentiated germ cell that contains both paternal and maternal chromosomes, at the end of meiosis she only produces germ cells with active imprinting gene copies, because the daughter later gives to her own offspring as a mother - regardless of whether Boy or girl again - only female imprinting genes further. Therefore, first of all, the muting - the methylation - on the original paternal chromosome must be removed. In other words, if a woman passes on paternal imprinting genes to her children, those original paternal genes must be given maternal imprint status. "If the imprint goes through the next germline, its status must be reversible," says Reik. “In fact, the imprints are erased relatively early in the germline and then reinserted. And it's absolutely fascinating to watch: Suddenly all the methylation is gone. We don't know exactly how this works, but it can now be precisely reconstructed mechanistically: all this takes place in mouse embryogenesis between day eleven and a half and day twelve and a half. On day eleven and a half after fertilization everything is still normal in the germ cells, the imprinting patterns are still there. And a day later they are all gone. So obviously after eradication there is a situation where the chromosomes are neutral in terms of their imprinting state." "And then how are the imprints set again?" "This is depending on oogenesis, as the development of female egg cells is called, or spermatogenesis, the process of sperm formation. In spermatogenesis, the imprints are set again sixteen days after fertilization, while in oogenesis it only starts again after birth. Again, we're talking about mice that give birth around the twentieth or twenty-first day after fertilization. After that, the markers for the future generation are set in the females again.” The first imprinted genes were discovered in mice in 1991, and surprisingly these experiments led some biologists to rethink the processes during pregnancy in general and the role of the placenta in particular rethink. All pregnant women have a placenta that gets thicker and thicker, weighing sometime between 500 and 900 grams, and is then expelled from the body in labor, usually after nine months. 3,000 years ago, this amazed people just as much as the arrival of a comet in the sky: the Egyptians stared in awe at this three centimeter thick disc with a diameter of up to 25 centimeters and often kept it. The Egyptians chose this cake as the seat of the soul after they noticed that many animals devoured it with the umbilical cord. Pharaohs had flags made with placenta emblems, which were always raised on celebratory occasions. Aristotle was in the 4th century BC. the first to describe the placenta in detail. The placenta, from the Latin placenta for cake, is the connecting organ between mother and embryo, later between mother and fetus, as the fetus is called from the fourth month of pregnancy. Where the fertilized egg attaches itself to the wall of the uterus, the cake is formed from parts of the uterine lining and an embryonic part, the surface membrane of the embryo. Internal fertilization and fetal development in the womb (uterus) are genetically determined and have been promoted by natural selection in the course of evolution: both serve to protect the embryo. If fertilization takes place outside the body, while only a small proportion of the abundant zygotes generally survive, in the case of internal fertilization an individual produces only a few zygotes in the course of his life, but these are correspondingly well protected. The various species and orders of placental animals developed explosively 70 to 40 million years ago; since then, evolution has produced placental mammals as diverse as elephants, rabbits, vampire bats, whales, deer, pigs, sea lions, rhinos, dogs, cats, rats, beavers, monkeys, great apes, and of course us humans. The placenta ensures that the fetus can breathe and is properly nourished, it serves as an excretory organ and as a filter to protect the baby from germs and harmful substances. The formation of a placental barrier allows the exchange of nutritional and metabolic products between maternal and fetal blood, separating the two circuits of embryonic and maternal blood vessels. The blood of the embryo is pumped through the arteries of the umbilical cord to the placenta and from there it flows back through the umbilical vein. Capillaries penetrate the maternal part of the placenta so that the unborn child can obtain oxygen, nutrients and liquid from the mother's blood. At the same time, waste products such as metabolic waste and carbon dioxide are returned. The placenta also produces hormones and estrogens as well as immune substances to fight off infections. In guidebooks for the modern family, the placenta is often described as an organ that connects the fetus to the mother via the umbilical cord, so that the future little one sees the light of day suitably well nourished. And some cell biologists also publish corresponding scientific articles in which the relationship between mother and fetus is presented as a particularly cozy event. The placenta seems, as the name suggests, to be primarily a maternal organ. If the placenta is the vital connecting organ between mother and embryo, then it should be genetically programmed for a smooth and harmonious pregnancy. What is good for the mother should also be good for the little one and vice versa. “Pregnancy should be the epitome of shared purpose, a sanctuary from any form of conflict, the perfect communion of convenience between mother and fetus. And the relationship between the two is as intertwined and mutual as any relationship can be," characterize Randolph M. Nesse and George C. Williams in Why We Get Sick: The Answers in Evolutionary Medicine (1997; Why We Get Sick . The New Science of Darwinian Medicine, 1995) the deceptive situation, because pregnancy should give at least every immunologist a headache: how can the mother's immune system accept the presence of a semi-foreign organism for nine months? Since half of the offspring's genome comes from the father, the maternal immune system should attack at least part of the embryo in the same way it rejects foreign tissue in a skin transplant. In fact, the part of the fetus that is closest to the mother's tissues contains few antigens that could provoke a rejection reaction. However, differences between father and mother in the Rhesus blood groups lead to complications; not necessarily during the first pregnancy, but in the second, when the mother has formed enough antibodies against the foreign blood group system: the mother's antibodies then penetrate through the placenta into the embryo's bloodstream and attack its red blood cells. What follows is an anemia in the unborn child, which can lead to cardiac arrest; if the embryo survives, what is known as haemolytic disease occurs: the severe breakdown of the newborn's red blood cells leads to the release of hemoglobin, which in turn is converted into the bile pigment bilirubin, which damages the brain cells. Pregnancy is therefore in principle an explosive affair, and this was only confirmed by the findings of Azim Suranis and Davor Saltors, according to which it is precisely the paternal genes that activate the formation of the placenta in mice. The identification of the first three imprinting genes Igf-2, Igf-2 receptor and H19 also fit into this pattern. Because while the Igf-2 gene in the mouse is a paternally activated gene, there is a maternally activated imprinting gene in the fetus with the Igf-2 receptor, which is exclusively responsible for controlling the breakdown of the insulin-like growth factor to accelerate. In other words, while the paternal genome tries to push the activities of this growth factor higher and higher, the maternal genes in the fetus try to thwart such genes. At first glance, this seems absurd. However, from an evolutionary perspective, Harvard University biologist David Haig concluded, it makes sense that since mother and future offspring share only half of their genes through ancestry, this could well lead to such wildly different reproductive strategies. Finally, genes that affect food resources have different interests depending on where they come from: paternal genes want more resources from the mother, maternal genes take fewer resources. Ultimately, three different types of genes can come into conflict in the womb, namely the mother's genes and the fetal maternal and paternal genes. Since the mother wants to have more offspring, she wants to distribute her resources evenly; none of her embryos, which she has to take care of in the course of her life, should receive too much or too little. The embryo's paternal genes, on the other hand, want growth hormones to work at full power; they want a large placenta with a large offspring. It is completely irrelevant to them whether the mother will have cubs again or not - especially since she could also get them from another male. From the point of view of modern evolutionary genetics, the placenta is therefore not a maternal organ for the benefit of the future baby, but an organ of the fetus which taps into the mother's blood and nutritional supply almost parasitically and without regard to losses. All of this can be compared to a dogged tug of war; two teams join forces to tug at the two ends of the rope, maintaining immense tension; if a teammate breaks in, everyone is suddenly on the ground; the system has collapsed, and something similar, David Haig suspects, is happening not only with female mice, but even in the human womb: although the various consequences of this arms race are rather minor, apart from a few extreme situations, there is undoubtedly an intense conflict between the mother and the fetus Genes that are characteristic of pregnancy. The sending of hormonal signals plays a decisive role here: the force with which the fetus wants to squeeze food out of the mother signals to the mother something about the suitability of the fetus; conversely, maternal resilience conveys to the fetus the costliness of its actions. Normally, as Haig points out in support of his theory, hormones are produced in small quantities, but as long as there is no conflict between the sender and receiver, they have a large effect within the body. Conversely, the situation in the womb is where the offspring are genetically programmed to produce increased doses of hormones while the maternal system arms itself to resist these manipulations. So the fetus releases the hormone human placental lactogen (HPL) to get more glucose for itself. Usually, when the blood sugar level reaches a certain point, a human body releases the hormone insulin produced in the pancreas, causing the glucose concentration to drop. HPL now binds the mother's insulin, causing her blood sugar level to rise. The mother, in turn, responds to the fetus's request with a higher insulin output, which only makes the fetus more greedy: it sends out even more HPL without further ado. Haig compares the struggle in the womb over the resources to be distributed, which begins after every meal a pregnant woman treats herself, to a loud bickering: »If a message can be transmitted in whispers, then why shout? Raised voices are often an expression of a conflict.« In total, the fetus secretes one to three grams of human placental lactogen into the mother's bloodstream every day, a fairly large amount that, strangely enough, is not required at all for the normal course of pregnancy: the weight of a newborn is normal even if the fetus has not produced any HPL at all. On the other hand, a high HPL output in women with stressed insulin production leads to so-called gestational diabetes; Although this is not directly noticeable, it can disrupt the regulatory mechanisms of the sugar balance in the long term: women who were diabetic during pregnancy are at increased risk of developing permanent diabetes in old age. The "war in the womb" theory sounds a bit over the top - at least to non-biologists or scientists uninterested in evolutionary explanations or who cannot imagine that different genetic forces are at work within an individual. But with their help, not only the gestational diabetes can be interpreted, but also one of the most dangerous complications during a human pregnancy: The so-called preeclampsia is the most common cause of damage to the health of the expectant mother, it affects three to six percent of all pregnant women and can sometimes lead to the death of mother and fetus. Dangerous high blood pressure sets in between the sixth and seventh month of pregnancy, which damages the mother's kidneys. This leads to protein excretion in the urine. This is because the fetus is trying to get more and more food; the fetus increases blood flow to the placenta by releasing hormones that constrict the maternal blood vessels, leading to increased blood pressure. On the other hand, during the course of the disease, the mother activates an enzyme that damages the blood vessels of the placenta and thus impairs the supply of oxygen and nutrients to the unborn child. “Indeed, this is a striking example of a possible maternal response to a signal sent by the fetus for more food to pass through the placenta. And the mother responds by producing substances to make less food pass through the placenta. In the case of preeclampsia, this leads to consequences that are not very pleasant for either the mother or the fetus,” comments Reik, who has been conducting sophisticated laboratory experiments with his research group in recent years to investigate the molecular mechanisms of tug-of-war in the womb and the imprinting genes involved. The Igf-2 gene was knocked out in mouse embryos, and the processes that normally transfer valuable nutrients from the mother to the fetus were disrupted. The result: the boys were 30 percent smaller than normal. "Igf-2 does indeed have a dramatic effect," Reik interprets the results. “It's the most important fetal growth gene that we know of. If we switch it off, the babies get smaller, and if there are two of them, then the babies are simply much too big.” For example, if children happen to inherit two gene copies from their father, this leads to what is known as Beckwith-Wiedemann syndrome in humans: the babies have a heart that is too big and a huge liver, they suddenly weigh 12 kilograms at birth. They are also subject to an increased risk of tumours, especially kidney tumours. According to Reik, this cancer risk is due to the function of Igf-2 as a cell division driver. “Amazingly, the Igf-2 receptor gene is not imprinted in humans.” “Yes, it is. This gene is imprinted in mice, but not in humans." "But surely that would mean that the war in the womb is much less dramatic in humans than in mice? Which in turn raises the fundamental question of how far findings from laboratory experiments with mice can be extrapolated to humans?” “I think the war in the womb is not just taking place in mice, but also in humans. Only the intensity of this war is different. And this intensity depends essentially on the individual's mode of reproduction: mice have many young in the uterus at the same time, while human mothers normally only have one. Also important is how often mothers have offspring from different fathers." "In humans or in mice?" "Both. Polyandry is the technical term for a mating system in which one female mates with multiple males. And the more intense the polyandry, the more intense the conflict should be and the stronger the selection pressure for imprinting. So the more different male genomes that apply..." "...to get something out of the maternal side?" "Yes, they always want to get more out of it. David Haig has put all of this into a mathematical model that I find very convincing. However, this does not answer the specific question of why the Igf-2 receptor is not imprinted in humans, but in general it can be plausibly explained why the details of this war in the womb depend on the living conditions, above all on the respective mode of reproduction of the species or the organism ." "But that doesn't answer the question of how far all these generalizations between mice and humans, whether in behavior or in specific genetic traits, are always so justified?" could figure out human diseases, that would be positive. Whenever I come across something new in the laboratory, I ask myself whether what is observed in the mouse also applies to me. It's a natural reaction. I don't find it that unusual that something is sometimes generalized that is actually not so generalizable. Therefore, the corresponding experiments have to be carried out again and again. For example, if one finds that the Igf-2 receptor is not imprinted in humans, one must consider why this is so. You can't use the mouse as an example to explain why the imprinting pattern is different in humans.« Around 60 imprinting genes have now been identified in mammals, and Reik suspects that there are probably between 100 and 200 such in humans genes A small number compared to the probably 30,000 to 40,000 genes the average human is said to have, but the imprinting genes have lasting implications: they are, in fact, the ultimate reason why, unlike many other species, at Parthenogenesis does not occur anywhere in mammals. Thanks to genomic imprinting, all those men who constantly and unscrupulously squander their sperm and later abandon the mother or contribute little or nothing to the children's upbringing need not fear that some woman might for one day renounce her services and carry an unfertilized egg to term . Because without the semen at fertilization there are no paternal imprinting genes, the embryo would quickly die. In general, the imprints must be set correctly in both the female and male germ line; errors play a particularly fatal role in some rare diseases. In Angelman syndrome, which occurs at a frequency of 1 in 20,000 in European populations, patients suffer from mental defects, lack of language development and epileptic seizures; they also like to laugh suddenly and for no reason, they generally behave in a very friendly manner. These are activities that are usually directed and controlled by the cerebral cortex. On the other hand, people with Prader-Willi syndrome have underdeveloped sex characteristics, muscle weakness, small hands and feet, they suffer from disorders in the central nervous system that are controlled by the limbic system, the feeling center of the cerebrum responsible for emotions and affects, and that over the course of the disease of the disease usually lead to insatiable appetite combined with obesity. Both syndromes were named after the physicians who first described them in the 1950s and 1960s. Both diseases are caused by mutations, often involving the loss of a section on chromosome 15. If copies of the paternal genes are lost, this leads to Prader-Willi syndrome; if the maternal genes are lost, the child suffers from Angelmann syndrome. Or a so-called imprinting error occurs when the imprinting pattern in the germ line is set incorrectly: Maternal imprinting of the paternal chromosome leads to Prader-Willi syndrome, while conversely paternal imprinting of the maternal chromosome causes Angelman syndrome. It is possible, Reik suspects, that many such mental disorders are caused by faulty imprinting processes. In fact, geneticists have now gone deep into the brain to study this strange phenomenon from the womb. In one experiment, for example, it was possible to combine embryonic cells from purely maternal chromosome copies – which should actually die off early in their development – with cells from a normal embryo. The animals continued to develop until birth; they are called chimeras because they were artificially assembled from two individuals with different genetic constitutions. The cells of these animals contain only maternal chromosomes as well as normal cells, chimeras are essentially a mixture of different tissues. Mice with mostly maternal genes had an oversized head protruding from the body, conversely, mouse chimeras with mostly paternal genes had a large body and small head, as if straight out of a bodybuilding gym. With the help of a kind of transmitter, even the distribution of the cells could be tracked: the maternal chromosomes were often found in those brain cells that control perception and conscious thinking, while the cells with the paternal chromosomes were located in the hypothalamus, where behavioral structures are processed that like Sex, food and aggression are important for successful survival. These findings have given rise to a variety of speculations. As Matt Ridley writes in Alphabet des Lebens (2000; Genome - The Autobiography of a Species in 23 Chapters, 1999): "If we assume that the placenta is a selfish organ that the paternal genes do not trust the maternal genes to produce, then it is the cerebral cortex is an organ that the maternal genes do not trust the paternal genes to produce. If we humans are like mice, we run around with our mother's thoughts and our father's whims (at least to the extent that thinking and whims are hereditary at all).' 'This experiment has been extremely complex, so it is not so easy to interpret', Reik comments the situation a little more soberly. “But there is now some evidence about what is called Turner syndrome that points in the same direction. In this syndrome, individuals who are female lack an X chromosome. And the girls with this X0 syndrome have different cognitive abilities depending on whether they have the single X chromosome from their father or their mother. If they got it from their father, certain defects were found, which often had to do with difficulties in so-called interpersonal relationships. And this in turn can be compared to normal XX and XY carriers: we men are XY and have inherited our X chromosome from our mother. And there is no doubt that men and women have different abilities when it comes to social interactions. Men tend to have defects in this respect. I think that is now generally accepted. And this could actually be related to imprinting processes. In principle, I think it will soon become clear how important imprinting processes are for behavior and perception. At this point, we're really just seeing the tip of the iceberg.” For about every 2,500 live births, there is one girl who has only a single X chromosome (X0); theoretically, the absence of this chromosome shouldn't be too noticeable, after all there's a second one to replace it, but these women have underdeveloped ovaries, are sterile and short stature, and although they have good verbal skills, they also have difficulty formulating abstract ideas such as carrying out activities that require a certain degree of planning. In 1997, David Skuse published the results of a study he and his colleagues at the London Institute of Child Health carried out on 80 girls and women between the ages of six and 25. Astonishingly, Skuse found differences in the social behavior of women, depending on the origin of the chromosome. If the women had their father's X chromosome (Xp), they were less open to rational arguments in interpersonal tensions, they had a dominant demeanor and were quick to insult others without realizing it themselves; in short, they were often unaware of the feelings of those around them. In contrast, the girls who inherited their X chromosome from their mother (Xm) were less domineering and aggressive in the interpersonal arena. From this, Skuse concluded that there must be genes on the X chromosome whose paternal or maternal expressions are differently imprinted, resulting in different male and female cognitive abilities and behavior.
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