How it all started
In 1961 the British geneticist Mary Lyon working at the MRC Harwell campus proposed that the genes on one of the two X chromosomes present in cells of female mammals get switched off during early development. She termed the process X chromosome inactivation or X inactivation for short. One of her inspirations for this idea was the work of Barr and Bertram who in 1954 reported that there is a distinct structure or body visible in the nuclei of XX female but not XY male cells. Mary suggested that the structure, now referred to as the Barr body, is the inactive X chromosome adopting a compacted configuration due to gene silencing.
Mary Lyon at the first X inactivation symposium in Novosibirsk, Russia, 1999
Photomicrographs from Barr and Bertrams original paper in 1954
In keeping with evolutionary theory, X inactivation evolved in order to balance the levels of gene products in XX females relative to males that have only one X chromosome. This solution contrasts dramatically with that in the fruitfly D. melanogaster where balance is achieved by doubling the levels of gene product on the single X chromosome in males, or in the nematode C. elegans where levels of gene product are halved on both X chromosomes in females (hermaphrodites).
Different systems for sex chromosome dosage compensation in classical model organisms
In X inactivation the choice of which X chromosome gets inactivated is normally random, but once a cell makes the decision, the same X chromosome stays inactive in all of that cells daughters, granddaughters etc throughout the life of the animal. A consequence of this is that female mammals are mosaics with groups of cells or clonal patches that have one or the other X chromosome silenced. It was by studying X-linked mutations that result in variegation (patches) on the coats of mice that led Mary to her insightful idea. A more common day to day manifestation of this is the orange and black fur patches seen in tortoiseshell and calico cats.
Coat colour variegation due to X chromosome activity in female mice and cats