In 1961, Mary Lyon, a researcher who studied genetics, published “Gene Action in the X-chromosome of the Mouse (Mus Musculus L.),” hereafter “Gene Action in the X-chromosome,” in the journal Nature. Lyon’s paper focuses on the workings of female sex chromosomes, or X-chromosomes, and their implications for gene expression. A chromosome is a structure in a cell’s nucleus that contains the DNA, or genetic information, for each individual. In her paper, Lyon proposes her X-inactivation hypothesis, which states that one of the two X-chromosomes in mammalian female cells becomes inactive during early development, silencing its genetic activity. By describing X-chromosome inactivation, Lyon provided an explanation for the mosaic patterns observed in some female mammals, where different regions of their bodies exhibit distinct traits based on the genes carried by the particular X-chromosome that is active in that region. “Gene Action in the X-chromosome” provided evidence that X-chromosome inactivation occurs, laying the basis for understanding sex-linked traits, gene expression, and X-linked genetic diseases that impact thousands of people.

Mary Frances Lyon studied gene expression and developed the theory of X-chromosome inactivation, also called Lyonization, during the twentieth century in the United Kingdom. The Lyonization hypothesis proposes that, even though females have two X-chromosomes and males have only one, one X-chromosome in females is always randomly inactivated, which causes males and females to have the same level of X-chromosome gene expression. Prior to Lyon’s hypothesis, scientists understood that there must be a biological way to compensate for the difference in X-chromosomes in males and females, but they did not know the exact mechanism. To investigate the topic, Lyon studied coat color in mice, a trait influenced by genes on the X-chromosome. Her resulting hypothesis highlighted X-chromosome inactivation as a mechanism for controlling gene expression in females without altering their DNA sequence. Through her research, Lyon aided scientists in understanding X-linked disorders, which laid the foundation for the development of gene therapies designed to treat X-linked disorders that affect hundreds of thousands of people globally.