Chromosomes and their problems
What are they?
Remember those long twisted chains of DNA molecules from those pretty pictures? Well, in reality they look a little different.
Firstly, a cell needs a lot of DNA. If you stretched all the DNA contained in one nucleus, you would get about two meters. In order for all this to fit into a nucleus whose dimensions are 6 microns (6 millionths of a meter), DNA is repeatedly twisted or, as scientists say, spiralized. Since the thickness of the DNA thread is very small, then when twisted into a kind of ball, it does not take up much space. But it is not completely twisted. Those parts of the DNA molecule that the cell needs at the moment do not spiralize or spiralize to a lesser extent. Only those parts that have recently worked or are about to start working resemble the famous image of a double helix (in fact, it is more correct to say a double screw).
Secondly, the DNA strand is not continuous (in the vast majority of species. In some, perhaps). I am not sure that this has any function, rather it just happened that way. One way or another, somatic (non-sex) cells of a human contain 23 different pairs of pieces from the mother and the same number from the father. These pieces are called chromatids. In turn, chromatids are combined into pairs of two identical pieces. Such pairs are called chromosomes.
In order to somehow organize the available information about chromosomes, people agreed to number them from longer to shorter. The numbering was chosen arbitrarily, since they float in the nucleus completely chaotically, divide synchronously, work simultaneously and have no fundamental differences (except for sex chromosomes).
Generally speaking, chromosomes of the thing are paired. Your n-th chromosome, which you got from your dad, is very similar to your n-th chromosome, which you got from your mom. In all people, n-th chromosomes are very similar to each other, but are very different from all those with other numbers. Except for sex chromosomes. Sex chromosomes exist in two types, X and Y (They are not very similar to each other, although to a greater extent than, for example, the fifth and sixth).
Until about 160 million years ago, the sex of our ancestors was determined similarly to the modern sex determination of most reptiles – depending on the temperature of the environment in which the egg developed (at that time, our ancestors still laid eggs). And then, at one fine moment, the SRY gene (or a very similar predecessor) appeared, which launched the determination of sex according to the male type, regardless of environmental conditions. I emphasize that it did not encode all the sexual differences between male and female, but only activated the existing genes that implemented these differences.
Since then, genes that are useful only for males, but useless or even harmful for females, have begun to accumulate in the Y chromosome. This is how it happened:
Normally, before a sperm/egg is created, there is a mixing of genetic material between the mother and father (in relation to the child, they are grandmother and grandfather) in order to load the sperm/egg with equal amounts of genetic material from both parents (in relation to the child, the grandmother and grandfather).
The closer genes are to each other on a chromosome, the more likely they are to be inherited by one offspring. Males with genes that are useful to males but harmful or useless to females left more viable sons if these genes were close to the sex-determining gene. Gradually, a stable set of sex-linked genes was formed, which traveled together from generation to generation and were passed mainly from father to son. A certain genetic mechanism also emerged that prevented them from exchanging genetic material with genes received from the mother (so that daughters would not get “male” genes that were dangerous to them, and sons would get them in full).
The fate of the X chromosome was no less interesting. It is present in the male body in a single copy, and in the female body in a double copy, as it was originally. Moreover, in the female body, when an egg is created, the genetic material of the father's X chromosome and the mother's X chromosome are mixed, as if they were not sex chromosomes, and in the male body, an exchange occurs between X and Y in areas that do not exceed 5% of their length (normally).
All of the above is true for most placental mammals, which include us, but there are other systems of sex determination in nature, so before applying this information to other groups of animals, it is advisable to check what type of sex determination they have.
CHROMOSOMAL MUTATIONS OF AUTOSOMES.
What happens to an organism if it loses one autosome (non-sex chromosome) as a result of a mutation? Due to the fact that autosomes exist in pairs (one from the father, the other from the mother), the organism will not lose the function of producing proteins encoded by the lost chromosome, but will produce much less of them. In turn, this will lead to an imbalance of important chemical compounds in the cells, as well as homozygosity of the alleles in them (as after incest), and ultimately to death at the stage of intrauterine development. If not the entire chromosome is lost, but only some part of it, then in principle there is a small chance of survival (the less is lost, the higher they are), but severe health consequences are almost guaranteed.
What happens if a person gets one extra chromosome? Mostly the same thing – an imbalance of synthesized protein and subsequent miscarriage. If you are very unlucky, then the miscarriage does not occur and a baby is born with terrible disorders in many organ systems. Higher nervous activity suffers the most. The most famous trisomy is trisomy on chromosome 21 – Down syndrome. The frequency is one case in about 700-800 births (it should be understood that there were significantly more embryos, but some of them were aborted, and some died in the womb due to natural causes). Less common are trisomies on chromosome 13 – Patau syndrome (1:7000-1:14000 births) and on chromosome 18 – Edwards syndrome (1:5000 births). The addition of any other additional autosome, as well as several of the listed ones at once, leads to intrauterine death with a 100% probability (or at least no survivors have been identified).
SEX CHROMOSOMES MUTATIONS.
As I wrote earlier, in most mammals, including humans, the male sex is determined mainly by the presence of an active SRY gene, and in its absence, the female sex is formed. Normally, this gene is located on the Y chromosome in the company of a small group of other genes (together they encode only 23 proteins), which help to form a healthier male organism. The second sex chromosome in men – X is completely identical to that in women and carries many more genes (encode about 800 proteins), which are mostly useful for both sexes.
What happens to the body if gonosomes (sex chromosomes) are lost or added? It would be logical to assume that everything is the same with them, but no. First, a question: how do women survive with double the secretion of X-chromosome genes? Why aren't their cells killed by the same protein imbalance that occurs when the number of autosomes increases?
The fact is that in the early stages of embryogenesis (only a few divisions) in each cell there is an inactivation (switching off) of one of the X chromosomes, which is preserved in all descendants of this cell, except for eggs. That is, there are two X chromosomes in a cell, but only one random one works at full capacity (in the body there are approximately an equal number of cells in which one or the other X chromosome is active). In the case of the presence of several X chromosomes in a cell, only one of them will not be inactivated. About 15% of genes avoid inactivation and mainly for this reason, the change in the number of X chromosomes does not pass without a trace.
Let's consider the following anomalies associated with sex chromosomes (hereinafter I call women and men people who are visually most similar to women and men, respectively):
X0 women. 1:1500 births. (Shereshevsky-Turner syndrome)
Short stature, underdeveloped sexual function, mental retardation and a bunch of other problems with other organ systems. As a rule, they are infertile, but there are exceptions.
XXX women. 1:700 births.
Outwardly, they do not differ from healthy women, although health problems including mental retardation and low fertility are quite common. They can give birth to children, including healthy ones. Excess of synthesized proteins is tolerated better than its deficiency. In addition, remember that most of the genes on the extra X chromosome are inactivated.
XXY males. 1:500-700 births of boys.
Externally it manifests itself rather weakly. You can notice a change in body proportions, sometimes breast development (slightly) in adolescence. Mental retardation is observed in 25-50% of cases, usually in a mild form. Sperm does not contain spermatozoa or contains very few of them. They cannot reproduce naturally, but with the help of IVF/ICSI it was possible to achieve the birth of healthy children.
XYY males. 1:1000 males.
It is almost not manifested externally, has no pronounced symptoms (remember that the Y chromosome codes for very few proteins and all of them are associated with purely male functions). Most carriers do not have any negative symptoms and do not even know that they are carriers. However, some consequences such as an increased risk of learning difficulties and sterility exist. And they are also on average slightly taller than normal men.
XYYY males 1:1,000,000
Mild to moderate developmental delay (especially speech), large, irregular teeth, poor enamel, tall stature, acne. Boys usually have normal genitals, but adult males often have hypogonadism (small testicles) and infertility. But with some luck, they can still have healthy children.
Tetrasomy and pentasomy, XXYY, XXXY, XXXXY, XXXYY, XYYYY and XXYYY males and XXXX, XXXXX females.
They are very rare (less than 1:18000 depending on the type). The more extra chromosomes, the more serious the consequences. First of all, intelligence (especially speech) and sexual function suffer. Other functions of the body also do not work very well, but in general not as bad as the reproductive system and the brain (in some, IQ drops to 20, although it can be 80). Also, taking this opportunity, I will note that even three extra sex chromosomes do not always lead to intrauterine death, unlike the guaranteed death with two additional autosomes.
XX men 4-5:100,000
De la Chapelle syndrome occurs when, during division of the sperm precursor, a piece of DNA from the Y chromosome is translocated (transferred) to the X chromosome. This creates an X chromosome that in fact carries both female and male genes. If among these male genes there is an SRY or some other (some) that initiates the development of the organism according to the male type (and the genes of the Y chromosome initiate such development, and do not encode all the characteristics of men), then the embryo will develop into an almost full-fledged man.
Due to an excess of female genes and the presumed inactivation of some male genes, XX men may have short stature, problems with sex hormones (usually not too severe) and everything that follows from a lack of male hormones (gynecomastia). [образование груди]poor hair growth, low libido, etc.), although it is often possible to meet completely phenotypically healthy XX men. The only symptom common to all is the complete absence of spermatozoa, and therefore incurable infertility (most likely due to the fact that not all genes from the Y chromosome are translocated to the X and they lack some protein needed to form sperm precursors). Here it is necessary to understand that usually the XX genotype in men is detected precisely when there are complaints of infertility, which means that in theory there may be some small percentage of unaccounted men with de la Chapelle syndrome with a fully functional reproductive system. If they exist, they may be fathers of either completely healthy daughters or XX sons like them (though the sons will be sterile with a higher probability).
XY females. 1:80,000 (Swayer syndrome)
Several different mutations in the Y chromosome can lead to similar consequences: underdevelopment of the sex glands (none at all. Instead, the gonadal strand is an underdeveloped organ that does not produce any hormones or gametes). Carriers of the mutation are outwardly indistinguishable from women, and often have all the organs that women are supposed to have, except for the ovaries and uterus. Due to the lack of female hormones, problems with other hormones, bone strength, and other minor, rather varied disorders arise. Treatment comes down to surgical removal of the underdeveloped sex glands, since they can often give rise to a cancerous tumor, and hormonal therapy to artificially create a normal hormonal background. They cannot have their own children, but with successful hormonal therapy they are able to bear a child from a donor egg.
X0/XY gender is a matter of luck.
If, at an early stage of division of a male XY embryo, one of the cells loses the Y chromosome, then all the descendants of this cell will also not contain it, while some of the cells unaffected by the mutation will contain it.
Depending on the ratio of X0/XY cells, the phenotype can vary from completely male to completely female, including the development of genitals of an intermediate type. However, most of them grow into more or less full-fledged men, some of whom can even have healthy children. X0/XY carriers often have developmental pathologies associated with the genitals, but usually not too severe. Psychomotor development is normal.
This is not a complete list of existing chromosomal mutations associated with sex. Deletions (losses) or duplications (doublings) of some fragment of the chromosome are possible, mosaicism X0/XX, XY/XXY and a bunch of other mosaicisms are possible. In addition, some mutations of single genes can lead to similar consequences (in fact, I described them in the paragraph about Swyer syndrome). It is not possible to describe all existing mutations due to their too large number and a fairly diverse clinical picture for most of them. Swyer syndrome was included in this article about chromosomal mutations, to which it does not belong, in order to demonstrate the existence of XY women.
To sum it up, I will say the following: in addition to the standard XY men and XX women, there is an incredible variety of men, women and some other people with other chromosomal combinations, most of whom have some or other problems with physical health and psyche, and, as a rule, the larger the mutation and the more cells it affects, the worse the health. All of the above varieties are very rare and for the most part they are quite easy to classify as male or female. People with an intermediate phenotype often have problems with hormones (and because of this, many other disorders of varying severity) and need lifelong therapy that will keep their hormonal background in a normal male or female state.
Author: Universal Publicist
