Lyon hypothesis

The Lyon hypothesis states that in cells with multiple X chromosomes, all but one is inactivated during mammalian embryogenesis. X-inactivation leads to clumped chromatin termed Barr bodies, which are generally considered inert. This formation of Barr bodies is called Lyonization.

In humans the X chromosome that is inactivated is determined by chance. In marsupials, however, the paternal X chromosome is always inactivated. Inactivation is achieved by methylation of the X chromosome DNA, a common way in which the cell silences particular genes. Certain animals have their coloring patterns dictated by this phenomenon. For example, female Calico cats have unique patterns of fur due to certain areas where different X chromosomes are inactived. The X chromosomes that are activated express different coloring genes and lead to their mosaic fur color.

However, there are now reports that women still express many genes from their inactive X chromosomes, and that different women express different genes from the inactive X. Research by Carrel and Willard (2005) indicates that 15% of the genes on the inactive X chromosome are actually active across all women, and a further 10% of genes were switched on in some women. Many of these genes are dominant genes covering for defective recessive alleles on the active X chromosome to cover such sex-linked disorders as haemophilia and color blindness.

The hypothesis was first stated by Mary F. Lyon in 1961 while she was studying the genetic consequences of radiation exposure, and therefore bears her name.