As I talked last week about
epigenetics, I found the example of X-Chromosome Inactivation extremely
interesting. So, I resolved to explain more about.
As
we know, one of the female X-Chromosome in each cell is inactivated by
methylation (epigenetic process) as a mechanism of dose compensation related to
the male quantity of gene expression. Half
of the female’s cells has a working X chromosome from her mother while the
other half has active X chromosome from her father. In this way, a cellular mosaicism
is result from the X inactivation. The choice of the X-Chromosome to be inactivated
is random. In the fetal development each cell chooses which X they will inactivate:
the one from the father or the one from the mother.
The
gene responsible for inactivating one X-Chromosome is called X inactive specific transcript (XIST). This
X-linked gene is transcribed in the chromosome that will be inactivated. Its
transcription causes methylation and modification of chromosome’s chromatin,
which makes the chromosome inactive. (Migeon, 2007)
The
female mosaicism provides to women a biological advantage. This is not
difficult to understand: a single X chromosome in males make them vulnerable.
Any mutation that affects a gene on their maternal X chromosome will be
expressed in 100% of their cells. In contrast, women have two X chromosome in
each cell: when there is a mutation in a gene on one of their X chromosomes, they
have a normal copy of that gene on another one. Because of X inactivation, the
mutation will be expressed in only half the cells (Migeon, 2007). Therefore,
X-linked diseases are more severe and lethal in men than in women.
According
to Migeon (2007), in the course of evolution, mammalians began with identical
sex chromosomes of reptilian origin. Then, the Y chromosome has been progressively
reduced in size and one of its genes became a sex-determining gene. As result
of gene’s losses, this chromosome has now less than 100 genes while X-chromosome
has about 1100 genes. Thus, mammals inactivate one of the two X chromosomes for
dosage compensation. Other organisms also make dose compensation but curiously
in a different way. Flies, for example, increase the expression of the single X
chromosome in the male to achieve the same production as that from the two X
chromosomes in the female.
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An example of female mosaicism caused by X-Chromosome
Inactivation: A mutation in a gene for sweat glands from one X-Chromosome affects
some parts of the body while tissues that express the normal X-Chromosome are
not affected.
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REFERENCE LIST:
Migeon, B. R. (2007). Why Females
Are Mosaics, X-Chromosome Inactivation, and Sex Differences in Disease. Gender Medicine, vol. 4, no. 2.
Fascinating and well explained. This is a definitely a case of when having more can be beneficial. Are there incidences when the body fails to recognize deleterious mutations on the x-chromosome, resulting in disease/disorder regardless of the presence of a “normal” x-chromosome? Great post.
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