Dosage compensation

In XX: XY sex determination, the amount of gene product encoded by the X-chromosome would be high in females (twice than produced in males). DC equalizes the amount of protein produced by X-linked genes in two sexes. In flies, DC is achieved by doubling the activity of the genes on X-chromosome of the male. In worm, C.elegans, it is achieved by halving of the activity of genes on both of the X-chromosome in females. In females that are heterozygotes at X-linked locus, 50% of the cells will express one allele and 50% will express the other allele. Thus protein produced by both alleles will be produced but not within the same cell.

In humans, females are hemizygous at the cellular levels for X-linked genes. Mary Lyon gave Lyon hypothesis which states that within each female cells, one of the two X-chromosomes become inactive and it is random. Random inactivation requires two steps: (a) the cell assesses or counts how many chromosomes are present, (b) one X-chromosome is selected to become the active X-chromosome and all others are silenced. Gene called Xist (X-inactivation specific transcripts) is active on the X-chromosome destined to become inactive, producing an RNA molecule that is quite large and lacks ORF, thus cannot be translated. This RNA product spread and coats the X-chromosome bearing the gene that produced them and inactivates the genes on it, probably by altering chromatin structure. This inactivation is of cis-acting. X-inactivation center (Xic) is the region located on the proximal end of the p-arm in humans (end toward centromere), its genetic expression occurs only in the inactivated X-chromosome. Other non-coding gene Tsix and Xite also play an important role. On the X-chromosome destined to be active, other genes repress the activity of Xist so that Xist RNA on this chromosome remains active.

The inactivated X-chromosome is called a Barr body which was identified by Murray Barr. It is darkly stained bodies in the nuclei of cells of females.

karyotype	phenotype	Barr bodies
XX	Normal	1
XY	Normal	0
XO	Turner	0
XXY	Klinefelter	1
XXYY	Klinefelter	1
XXXY	Klinefelter	2
XXXXY	Klinefelter	3
XXX	Triplo-X	2
XXXX	Poly-X female	3
XXXXX	Poly-X female	4