
Mary F. Lyon
Wolf Prize Laureate in Medicine 1996/7

Mary Frances Lyon
Affiliation at the time of the award:
Medical Research Council, Mammalian Genetics Unit, England
Award citation:
“for her hypothesis concerning the random inactivation of X-chromosomes in mammals.”
Prize share:
None
Dr. Mary Frances Lyon (born in 1925, England) commenced her academic journey at Girton College, part of the University of Cambridge, in 1943. Her coursework included zoology, physiology, organic chemistry, and biochemistry, with a primary focus on zoology. As she delved into her studies at Cambridge, her interest in embryology blossomed. Subsequently, she pursued her Ph.D. under the guidance of Ronald Fisher. Continuing her doctoral studies, she relocated to the University of Edinburgh, completing her research under the supervision of Douglas Falconer.
Mary Frances Lyon put forward early in 1961 a disarmingly simple yet elegant hypothesis regarding the random inactivation of one of the two X-chromosomes carried by female mammalian cells.
Somatic cells of male mammals carry only one X-chromosome, whereas cells of females carry two. Since many of the genes encoded on the X-chromosome must be expressed to the same extent in both male and female cells, some mechanism must exist to compensate for this imbalance in X-chromosome number. The Lyon Hypothesis was put forward as a means of achieving this dosage compensation for the genes encoded on the X-chromosome. In a concise one-page paper (Nature 190: 372, 1961), Lyon argued that this balance was brought about by the random inactivation of either the paternally or maternally inherited X-chromosome in each female cell and that this inactivation occurred early in embryonic development.
The original arguments were made on the basis of genes expressed in the mouse, including coat color genes, but this hypothesis explained X-chromosome behavior in many – if not all mammals. Over the years her hypothesis has been confirmed by much indirect and, more recently, direct evidence focusing on the gene(s) responsible for this behavior.
