Mary Frances Lyon

Observation of X chromosome inactivation using mice

Contributed by: Brandon Beall




Animals, Europe, Fundamental research, Genes, Genetic material, Genetics, Historical figure, Lab, Medicine, Molecular biology, Observational, Woman, X-linked inheritance



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Rastan, S. Mary F. Lyon (1925–2014)Nature 518, 36 (2015) link



Slide 1: Researcher’s Background

Mary Frances Lyon–an English geneticist and Cambridge University alumni–is renowned for her work regarding mutagenesis and, specifically, gene dosage. Her discovery of X-inactivation, often referred to as “Lyonization” in her honor, is the cornerstone of many successive gene dosage and chromosomal regulation studies.

Biography in brief

Born in 1925, Mary Lyon was raised in Norwich, England when the field of genetics had still yet to bud into the molecular stage. Lyon pursued her interest in science at Cambridge University where she studied zoology. Lyon went on to receive a PhD at Cambridge working with Ronald Fisher, a famous statistician and geneticist.

Lyon went on to conduct her x-inactivation research at the Medical Research Council Radiobiology Unit in Harwell, England. She continued to conduct her experiments with mice, a model system she had grown familiar with during her time as a doctoral student. Lyon eventually rose to the top of the genetics division at Harwell, leading research and taking on the next new batch of students.

While genetics (and science in general) remained a male-dominated field during her active years–emphasized by the fact that female graduates at Cambridge University were only awarded “titular degrees”–Lyon garnered her due respect in the scientific community. Lyon was awarded the Royal Medal of the Royal Society and several other rewards throughout the late 70s and earlier 2000s.

Is (or was) their research under-valued because of their identity?

Are there other scientists/research examples that this example can replace or be added to?
Mary Lyon’s work should be used more commonly in genetics curriculum to describe gene dosage and gene regulation among sex-linked chromosomes.


Slide 2: Research Overview

Take home message of study

Random inactivation of either the maternal or parental X chromosomes in females is the cause of genetic mosaicism in sex-linked traits.  

Study system

Lyon’s research involved mice, a model organism for genetics research.


Slide 3: Key Research Points

Main figure

The figure shows the logic behind chromosome x-inactivation.  A gene for fur color is sex-linked in cats.  Two alleles, an orange and a black allele, exist for this gene. In males (XY), the fur color will always be either brown or black because there is only one copy of the X chromosome and therefore only one possible allele of the gene.  In females (XX), the fur color will be uniform if both parents pass on the same allele for fur color.  In females where parents pass on different alleles, a mosaic pattern of fur color may be observed.  This pattern arises because random inactivation of the X chromosome will produce cells that express both the orange and black allele.


Societal Relevance

Lyon’s research arrived in a decade where many mechanisms of molecular biology and genetics were largely unexplored.  Lyon provided an example of gene dosage in action, a phenomena that is critically important to modern geneticists.  Lyon’s work also enabled the discovery of the Xist gene, which is responsible for the silencing of one of the X chromosomes.  This is one of the first well-researched descriptions of gene regulation, another concept that has grown only more and more relevant with the passing decades.

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