Mary Lyon, the discoverer of X-inactivation, has died, according to the Medical Research Council Harwell. She was 89.
"[W]ith the discovery of X inactivation and her work on the t complex, she brought fundamental and profound insights to mammalian genetics and the genetic bases of disease," says the MRC Harwell statement.
As Lyon told PLOS Genetics' Jane Gitschier in 2010, Lyon had more opportunities to pursue science as a career because of the onset of World War II, which restricted the number of men who could go to university and perform research.
Lyon focused on mouse genetics and began working on the pallid mutant during her PhD, work that she continued through her postdoc. She also began to study the mutagenic effects of radiation, a topic of concern in the post-WWII and atomic bombing days. From there, she moved to Harwell where there was more space for the mice they needed for their mutagenesis projects
During this time, she became aware of X-linked mutants like Tabby and mottled, and began to wonder how a male mottled mouse could pass on that trait to some of his daughters while other daughters and sons were normal. The affected daughters themselves had affected daughters and sons, though the sons died — they were acting, Lyon told PLOS Genetics, like they had a mutant gene on their X chromosome. But how, then did the original male mottled mouse arise?
Lyon said that he likely had a mutation that occurred early in his development that gave him cells with mutated X and cells with a normal X chromosome.
"[I]t occurred to me that if that explanation of him having two types of cells applied to his pattern, could it not also apply to the pattern of his daughters?" Lyon said. "His daughters could have two types of cells, one with the mutant gene active and one with the normal gene active."
Lyon also recounted reading in the literature that XO mice are fertile and Susumu Ohno's report saying that that the sex chromatin in the nuclei of female mammals contains one highly condensed X chromosome.
"So I put all those things together and came up with the idea of X-chromosome inactivation," she said.