Inactivation of X chromosome (Lionization)

Sex chromosomes (X and Y chromosomes)

Genetic information of living organisms is stored in chromosomes located in the "nucleus" of cells. The human nucleus contains 23 pairs of 46 chromosomes, 23 pairs from the father and 23 pairs from the mother. 22 pairs of 44 chromosomes out of the 46 chromosomes are called autosomes, which are the most common type of chromosomes in the world.

Numerous genes are present. The remaining one or two pairs of chromosomes are called sex chromosomes, and genes are also present here, but they contain genes related to sex determination. Two types of human sex chromosomes exist: X and Y chromosomes.

In humans, females have two X chromosomes (XX) and males have one X chromosome and one Y chromosome (XY), and a region on the Y chromosome called SRY has been shown to play an important role in the expression of genes necessary to become male.

lionization

The Y chromosome, which determines male identity, has only about 50 genes, not many, and its main role is to determine sex, whereas the X chromosome has more than 1,000 genes, many of which are important for the life of the organism.

Then, is there any difference in the amount of protein, etc., produced based on the genes in the X chromosome between women with two X chromosomes and men with only one X chromosome?

The answer is no.

It is known that the function of proteins produced from the X chromosome is almost the same in women, who have two X chromosomes, as in men. If the expression levels of important life-supporting genes on the X chromosome were higher in females, there might have been a greater difference between males and females.

In fact, one of the two X chromosomes possessed by females is functionally inactivated so that it can only function as a single X chromosome, virtually the same as a male chromosome. This mechanism of X chromosome inactivation is called "lyonization. (The name comes from Mary Lyon, a British geneticist who proposed this hypothesis in the 1960s.)

Since which X chromosome is suppressed in "lionization" is determined for each cell at birth, any difference in the function of the two X chromosomes results in a "mosaic state" in which each cell has different characteristics.

Example of lionization: How a tortoiseshell cat is made

It is difficult to understand the concept of "lionization" through general explanations, but an example that is familiar and helps us understand how it works is the "tortoiseshell cat. 

Tortoiseshell cats, which you may often see around you, have three colors of fur: white, black, and brown. Of these three colors, the gene that determines whether the fur is brown or black is located on the X chromosome ("O" for brown and "o" for black). If a female cat has both "OO" genes on her X chromosome, she will have brown fur all over, and if she has "oo" genes, she will have black fur all over. Then, what would the coat color be if the cat had an "Oo" gene combination with one brown and one black gene?

According to the "lionization" mechanism, one of the X chromosomes is suppressed, so it would seem that only one color, either brown or black, appears, but as mentioned earlier, each cell determines whether the X chromosome is suppressed, so brown and black cells exist in a mosaic state, mixed together randomly. Therefore, the brown and black hairs are mixed together to make a "tortoiseshell" cat.
　
Male tortoiseshell cats are rare.
Now, up to this point, our discussion of tortoiseshell cats assumed a female cat with two X chromosomes.
So do male tortoiseshell cats exist?

Males have only one X chromosome, so they can only have either black or brown genes.So, basically, tortoiseshell cats are not born.
However, if a chromosomal abnormality occurs, resulting in three "XXY" sex chromosomes and two X chromosomes, "lionization" may occur, resulting in a tortoiseshell cat. The probability of a male tortoiseshell cat with an "XXY" chromosome abnormality is said to be about 1 in 30,000, making it extremely rare.

This chromosomal abnormality that results in "XXY" is the cause of a genetic disorder called Klinefelter's syndrome. This will be explained in more detail later.

Genetic abnormalities related to sex chromosomes

A number of genetic disorders caused by sex chromosome abnormalities have been reported. Here we will introduce some of the most common disorders and consider how "lyonization" is involved in these diseases.

Klinefelter's syndrome (XXY, XXXY, etc.)

Genetic disorders with two or more X chromosomes, such as "XXY" in the male tortoiseshell cat example above, are called Klinefelter's syndrome, a disorder that occurs in males because they have a Y chromosome and is thought to occur in about 1 in 500-1000 people.

Although one or more X chromosomes are present, it is not a fatal genetic abnormality because the function of the excess X chromosome is suppressed by "lyonization. Symptoms are often mild, and it is believed that many people are unaware that they have the syndrome until they are diagnosed with infertility, or they live their lives without knowing they have the syndrome.

However, symptoms such as testicular atrophy and azoospermia still appear because the X chromosome contains a "pseudoautosomal region," a gene that is not inactivated by ligation, and therefore more genes on the X chromosome are expressed in this region.

For more information on symptoms and treatment,This sitefor more information.

Turner's syndrome (XO)

Turner's syndrome" is another disorder related to a sex chromosome abnormality, but it refers to a series of syndromes that occur in women with only one X chromosome (XO). The frequency is found in approximately 1 in 2,500 people.

A normal woman with two X chromosomes (XX) also has one of them inactivated by "lionization" and is basically functioning with only one X chromosome, which may not appear to be significantly different from Turner syndrome, which has one X chromosome. However, Turner syndrome, like Klinefelter syndrome, is not a fatal genetic abnormality, but it does cause clinical symptoms such as short stature and amenorrhea because only one gene in the "pseudoautosomal region" of the X chromosome, which is not inactivated, is present in Turner syndrome compared to the normal. This is why clinical symptoms such as short stature and amenorrhea appear.

summary

Lionization" is an important mechanism that regulates gene expression in females with two X chromosomes by inactivating one of them. It is also involved in the development of tortoiseshell cats, and the effects of "lionization" can be observed close at hand. Lionization" also plays an important role in diseases related to sex chromosome abnormalities, such as Klinefelter's syndrome and Turner's syndrome, and this mechanism is thought to make the symptoms of these diseases less severe than those caused by other chromosome abnormalities.