In human and other mammals, the dosage compensation is followed by the inactivation of one of the X chromosomes in females so that both males and females have only one functional X chromosome per cell. In females, the coiling of inactive X chromosome into heterochromatin, a dark spot becomes visible in the nucleus of female cell, which is known as X-chromatin or Barr body. Thus Barr body is the inactivated X chromosome, which does not exist in the somatic cell nuclei of normal males. But Barr body is found in the nucleus of the cell of normal females. The hypothesis, named after Mary Lyon who stated it, suggesting that dosage compensation in mammals is by inactivation of all but one X chromosome in cells with more than one X chromosome.
The Barr body, visible in some female mammalian cells, is an inactivated X chromosome. Sexually aneuploid individuals provide evidence for this hypothesis. Aneuploidy means the possession of an abnormal number of chromosomes. An extra or missing chromosome is the characteristic of Aneuploid individuals. Females lacking one X chromosome exhibit Turner’s syndrome (designated 45 XO), while males with an extra X-chromosome exhibit Klinefelter’s syndrome (designated 47 XXY). The number of cells of some Aneuploid individuals is shown in the following figure:
The sex testing of Olympic athletes includes a count of Barr bodies. Males masked as females can be identified as they have no Barr bodies. The inactivation of X chromosomes occurs because of inactivation of maternally derived X-chromosome in some and the inactivation of paternally derived X-chromosome in others. Thus we obtain the descendants of a particular cell having the same X inactivated.
Calico cats having patches of color show mosaicism due to dosage compensation. There are several loci, that control the coat color in cats, but only one X-linked locus is involved in producing calico individuals. Normally, all calico cats are females. The sex-chromosome aneuplioidy causes the male calico cats. The heterozygous females possessing allele for color blindness exhibit normal color vision due to the presence of other normal clones.
In heterozygous females also the X inactivation can be seen for some X-Iinked traits. Ectodermal dysplasia is one such condition. People with ectodermal dysplasia may not sweat or may have decreased sweating because of the lack of sweat glands. Its symptoms also include few missing or abnormal teeth or the patches of skin. The random inactivation of different X chromosomes during development, the genetically identical female twins represent the considerable difference in the location of patches of skin lacking sweat glands. Thus, in genotypically identical individuals also, the X-chromosome inactivation may bring phenotypic differences.
Enzyme G-6PD results from the X-inactivation in females heterozygous for an X-linked gene. The G-6PD gene has alleles in two enzymatic forms, G-6PD type A and G-6PD type B for the heterozygous individual. Generally, half the cells express G-6PD type A enzyme, while the remaining express G-6PD type B enzyme. Thus, the validity of the hypothesis that X-inactivation is clonally transmitted gets confirmed. The heterozygous females can be detected through the phenomenon of random X-inactivation for a particular trait or enzyme.
Certain cells of this heterozygous female exhibit the gene expression like deficient male cells and some like normal female cells. Because of possessing ability to transmit both of their X chromosomes to their progeny, the X chromosomes inactivation is a reversible process. The case of hemizygous male progeny receiving either of the X chromosomes of the mother with equal probability signifies it. The inherited mental retardation in humans is the example of the abnormal reactivation of the heterochromatic X chromosomes.
In Drosophila: The mechanism of Dosage compensation occurs is different in fruit flies (Drosophila) from the mammals. The X chromosome to autosome ratio determines the sex as no barr bodies are found in fruit flies. In Drosophila, like in humans, male cells have a single X chromosome, while female cells have two. By increasing the transcriptional activity of genes on a single X chromosome in male cells with respect to each of the X chromosome in female cells, the dosage compensation can be obtained. The hyperactive X-chromosome of male reached to the activity level of both of the female X chromosome. This hyperactivity of X-chromosome can be observed as “puffed” bands in the salivary gland chromosomes. While in mammals, the inactive X-chromosome gets appear in condensed form.