| X Inactivation |
Having a single copy of any chromosome other than the X or the Y is lethal in humans; however, only one X chromosome is needed for normal development to occur. Therefore, the evolutionary process that resulted in a loss of genes from the Y chromosome would seem to have presented a problem. At least two possible mechanisms could balance gene expression between the two X chromosomes in females, versus only one X in males. Gene activity on the one X present in males (relative to the ancestor before the evolution of the XY system) could be increased so that these genes produce twice as much in males as in females. Alternately, X-linked genes could have their activity decreased in females. The first mechanism is seen in some insects, including Drosophila, while mammals use a special variant of the second, called X-inactivation. In X-inactivation, female embryos randomly inactivate one X chromosome in each cell, resulting in only one functional copy of X-linked genes in both males and females.
X-inactivation requires a locus on the X, called the X-inactivation center. At this locus, inactivation occurs in response to a developmental cue, which is present only at specific stages of embryo development. Inactivation occurs because of a specific type of RNA, which binds to one X chromosome, preventing transcription of the genes on this particular copy. In addition, enzymes add methyl groups to the DNA of the inactive X, resulting in repression of transcription. The inactivated X is visible during interphase in mitosis as a condensed chromosome, called a Barr body. It replicates in the S (synthesis) phase of the cell cycle later than does the active copy. Inactivation of one of the two X copies in a female leaves only one active
X chromosome in any cell. An individual who has three X chromosomes has two inactivated copies of the X, producing two Barr bodies.
Because the X is inactivated randomly in cells, one cell could have the maternal X inactivated, while the adjacent cell could have the paternal
X inactivated. This causes a pattern of gene expression called mosaicism, which occurs when different alleles of X-linked genes are expressed in different cells. A classic example of mosaicism is the female calico cat, which inherits an X-linked allele for yellow coat color from one parent and an
X-linked black allele from the other. One or the other color is expressed in patches of the coat that represent cells descending from parental cells with either an active maternal X or paternal X.