Although originally discovered in Drosophila, phenomenon of dosage compensation later received attention in higher animals and plants, especially in mammals. It has been demonstrated that in the homogametic XX female individuals, one X-chromosome gets characteristically condensed and inactivated. Such chromatin materialhas also been described as facultative heterochromatin, since it becomes inactive in certain part of the life cycle and resumes activity before entering the germ line. This is in contrast to constitutive heterochromatin (found near centromeres and other part of the chromosomes), which remains permanently heterochromatic and inactive. The phenomenon of inactivation of X-chromosome was confirmed by the observation of a Barr body (first observed by Barr and Bertram in 1949 in female cat and later identified as X-chromosome by Ohno et al., 1959). Later Lyon (1972) confirmed the existence of Barr body in normal females, superfemales and in Klinefelter males. Since it was found that whenever the number of X-chromosomes was two or more than two, the number of Barr bodies was one less than the number of X-chromosomes (e.g. one Barr body in XX female; two Barr bodies in XXXY males, etc.), it was established that in the normal female only one active X-chromosome is found. This is also referred sometimes as Lyon's hypothesis after the name of the lady scientist M.F. Lyon of U.K.
Which of the two X-chromosomes remains active in female individuals, is determined at the early stages of development. It was observed by Lyon in 1961, that each of the paternal and maternal X-chromosomes has a chance to become inactive. In other words, the inactivation of a X-chromosome is a random phenomenon. This could be shown by utilizing an individual which is heterozygous for coat colour in mice. It was shown that such heterozygous mice had a variegated phenotype, because while in some cells the chromosome carrying the normal allele was inactivated giving the mutant phenotype, in other cells the chromosome carrying the mutant allele was inactivated giving these cells the wild type phenotype. When the gene for coat colour was located on an autosome, such variegation was not observed suggesting that inactivation takes place only in X-chromosome and not in autosomes. Variegation was also absent in mice having XO genotype, since no inactivation takes place in such a case.
There is no general rule for the time at which the inactivation will take place leading to formation of facultative heterochromatin. In mammals, the inactivation usually takes place in early embryogenesis. In mouse, late replicating heterochromatic X-chromosomes can not be detected until late blastocyst. Similar situation has also been observed in certain other mammal cells. In mammals, it has also been observed that the condensed 'Barr-body', characteristic of somatic cells, is absent from the female pre-meiotic cells.
The process of inactivation, therefore, seems to be reversed in the germ cells, so that all female gametes or eggs will carry an active X chromosome. The fate of the X-chromosome carried in an egg will depend upon whether it goes to a male individual or to a female individual. In a female individual they may again have a chance of inactivation while in male they will have no chance of becoming inactive.