In 1961, Mary Frances Lyon proposed in Nature that one of the two X chromosomes in every cell of female mammals is inactivated. This, she argued, occurs to prevent XX female cells from expressing twice as many X-linked gene products as XY male cells.
Lyon’s X-chromosome inactivation hypothesis had profound implications for clinical genetics and developmental biology. For instance, it helped researchers to elucidate the genetic basis of many X-linked diseases, such as Duchenne muscular dystrophy. It also led, 30 years later, to the discovery of the Xist gene, which helped to spawn a whole field of research on the role of long non-coding RNA molecules in regulating gene expression. The non-coding Xist RNA is the master switch that turns off the X chromosome. It also explains some everyday phenomena, such as the patchy colouring of tortoiseshell cats.