Mary Lyon and the hypothesis of random X chromosome inactivation

The 50th anniversary of Mary Lyon's 1961 Nature paper, proposing random inactivation in early embryonic life of one of the two X chromosomes in the cells of mammalian females, provides an opportunity to remember and celebrate the work of those involved. While the hypothesis was initially put forward by Lyon based on findings in the mouse, it was founded on earlier studies, notably the work of Susumu Ohno; it was also suggested independently by Beutler and colleagues using experimental evidence from a human X-linked disorder, glucose-6-phosphate dehydrogenase deficiency, and has proved to be of as great importance for human and medical genetics as it has for general mammalian genetics. Alongside the hypothesis itself, previous cytological studies of mouse and human chromosomes, and the observations on X-linked mutants in both species deserve recognition for their essential role in underpinning the hypothesis of random X-inactivation, while subsequent research on the X-inactivation centre and the molecular mechanisms underlying the inactivation process represent some of the most outstanding contributions to human and wider mammalian genetics over the past 50 years.