Mary F. Lyon

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Mary Lyon

FRS
Mary Frances Lyon.png
Born
Mary Frances Lyon

(1925-05-15)15 May 1925 [1]
Norwich, England
Died25 December 2014(2014-12-25) (aged 89)
Alma mater University of Cambridge (BA, PhD)
Known for X-chromosome inactivation [2]
Awards
Scientific career
Doctoral advisor Ronald Fisher
Doctoral studentsSohaila Rastan[ citation needed ]
Elizabeth Fisher (co-supervised with Steve Brown)

Mary Frances Lyon FRS [3] (15 May 1925 – 25 December 2014) [4] was an English geneticist, best known for her discovery of X-chromosome inactivation, an important biological phenomenon. [5] [6] [7] [8] [9] [10] [11]

Fellow of the Royal Society Elected Fellow of the Royal Society, including Honorary, Foreign and Royal Fellows

Fellowship of the Royal Society is an award granted to individuals that the Royal Society of London judges to have made a 'substantial contribution to the improvement of natural knowledge, including mathematics, engineering science and medical science'.

Geneticist biologist who studies genetics

A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms.

Contents

Childhood and education

Mary Lyon was born on 15 May 1925 in Norwich, England as the eldest out of three children of a civil servant and a schoolteacher. She was educated at a grammar school in Birmingham. During that time, she said, she became interested in science thanks to a good schoolteacher [12] and nature books she won in an essay competition. [13] During the Second World War, she pursued her studies at Girton College, Cambridge at the University of Cambridge, [14] where she read zoology, physiology, organic chemistry and biochemistry, with zoology as her main subject. At this time, only 500 female students were allowed to study at the university, in contrast to more than 5,000 men. Furthermore, the woman received only a "titular" degree, simply put, she wasn't awarded a degree, despite attending the lectures with men, taking the same practical courses and passing the same exams as the men. [13] During that time she became interested in embryology. She went on to do her PhD with R A Fisher, who was Professor of Genetics in Cambridge, where she characterised a mutant mice strain with a 'pallid' mutation and published the research. During the course of her PhD she moved to Edinburgh.

Girton College, Cambridge college of the University of Cambridge

Girton College is one of the 31 constituent colleges of the University of Cambridge. The college was established in 1869 by Emily Davies, Barbara Bodichon and Lady Stanley of Alderley as the first women's college in Cambridge. In 1948, it was granted full college status by the university, marking the official admittance of women to the university. In 1976, it was the first Cambridge women's college to become coeducational.

University of Cambridge University in Cambridge, United Kingdom

The University of Cambridge is a collegiate public research university in Cambridge, United Kingdom. Founded in 1209 and granted a Royal Charter by King Henry III in 1231, Cambridge is the second-oldest university in the English-speaking world and the world's fourth-oldest surviving university. The university grew out of an association of scholars who left the University of Oxford after a dispute with the townspeople. The two 'ancient universities' share many common features and are often referred to jointly as 'Oxbridge'. The history and influence of the University of Cambridge has made it one of the most prestigious universities in the world.

Ronald Fisher British statistician, evolutionary biologist, geneticist, and eugenicist

Sir Ronald Aylmer Fisher was a British statistician and geneticist. For his work in statistics, he has been described as "a genius who almost single-handedly created the foundations for modern statistical science" and "the single most important figure in 20th century statistics". In genetics, his work used mathematics to combine Mendelian genetics and natural selection; this contributed to the revival of Darwinism in the early 20th-century revision of the theory of evolution known as the modern synthesis. For his contributions to biology, Fisher has been called "the greatest of Darwin’s successors".

Research

After her PhD (awarded 1950 [15] ), Lyon joined the group of Conrad Hal Waddington, with whom she worked in the last part of her PhD. The group was funded by the Medical Research Council to investigate mutagenesis and the genetic risks of radiation. In addition to the 'pallid' mutation mice, she studied mutations such as 'ataxia' (a nervous mutation which caused walking difficulties in the mice) and 'twirler' (a mutation which induced inner ear issues, causing the mice to shake their heads and walk in circles due to lack of balance).

Mutagenesis is a process by which the genetic information of an organism is changed, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. In nature mutagenesis can lead to cancer and various heritable diseases, but it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.

Radiation Waves or particles propagating through space or through a medium, carrying energy

In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes:

In 1955, her group moved to the MRC radiobiology unit in Harwell, where there was room for more mouse facilities. There she continued to investigate the mouse mutations. She also scrutinised a 'mottled' mutant, which had a different effect on male and female mice: male embryos sometimes died, and the surviving males had white coats, but females lived and were variegated. Through calculated and deliberated breeding of mutants, she investigated the transition of the mutation and concluded that the mutation was positioned on the X chromosome. This, together with new findings at that time concerning the X chromosome, led her to hypothesize about X chromosome silencing. [13]

Hypothesis Proposed explanation for an observation, phenomenon, or scientific problem

A hypothesis is a proposed explanation for a phenomenon. For a hypothesis to be a scientific hypothesis, the scientific method requires that one can test it. Scientists generally base scientific hypotheses on previous observations that cannot satisfactorily be explained with the available scientific theories. Even though the words "hypothesis" and "theory" are often used synonymously, a scientific hypothesis is not the same as a scientific theory. A working hypothesis is a provisionally accepted hypothesis proposed for further research, in a process beginning with an educated guess or thought.

Lyon published many peer-reviewed papers on radiation and chemical mutagenesis and on studies of mutant genes. [16] She also did extensive work on the mouse t-complex. [17] [18]

She was head of the Genetics Section of the MRC Radiology Unit at Harwell from 1962 to 1987. Although she retired from research in 1990, according to an interview from 2010, she was still active in the laboratory a few times a week. [13]

X-inactivation

It was while working on radiation hazards in 1961 that she discovered X-chromosome inactivation, for which she is best known, [14] and the phenomenon is sometimes known as Lyonization in her honour. Her subsequent research helped elucidate the genetic control mechanisms of the X chromosome and helped explain why female 'carriers' of X-linked genetic disorders can display mild symptoms. [19]

Awards and honours

Lyon was elected a Fellow of the Royal Society in 1973, [3] a Foreign Associate of the US National Academy of Sciences, and a Foreign Honorary Member of the American Academy of Arts and Sciences. In 1994 she won the Mauro Baschirotto Award in Human Genetics, in 1997 the Wolf Prize for Medicine, for her hypothesis concerning the random inactivation of X-chromosomes in mammals. In 1997 she also received the Amory Prize, for genetic discoveries relating to mammalian sex chromosomes. [20] In 2004 she was awarded the March of Dimes Prize in Developmental Biology. In 2006 she received the Pearl Meister Greengard Prize awarded by the Rockefeller University.

Since 2015 The Genetics Society has awarded the Mary Lyon Medal in her honour.

Other awards and honours include:

Her nomination for the Royal Society reads:

Related Research Articles

ENU chemical compound

ENU, also known as N-ethyl-N-nitrosourea (chemical formula C3H7N3O2), is a highly potent mutagen. For a given gene in mice, ENU can induce 1 new mutation in every 700 loci. It is also toxic at high doses.

Seymour Benzer American geneticist

Seymour Benzer was an American physicist, molecular biologist and behavioral geneticist. His career began during the molecular biology revolution of the 1950s, and he eventually rose to prominence in the fields of molecular and behavioral genetics. He led a productive genetics research lab both at Purdue University and as the James G. Boswell Professor of Neuroscience, Emeritus, at the California Institute of Technology.

X-inactivation Inactivation of copies of X chromosome

X-inactivation is a process by which one of the copies of the X chromosome is inactivated in some female mammals. The inactive X chromosome is silenced by it being packaged in such a way that it has a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome. The choice of which X chromosome will be inactivated is random in placental mammals such as humans, but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell and its descendants in the organism. Unlike the random X-inactivation in placental mammals, inactivation in marsupials applies exclusively to the paternally derived X chromosome.

Martin Evans Developmental biologist, winner of Nobel Prize in Physiology or Medicine 2007

Sir Martin John Evans is a British biologist who, with Matthew Kaufman, was the first to culture mice embryonic stem cells and cultivate them in a laboratory in 1981. He is also known, along with Mario Capecchi and Oliver Smithies, for his work in the development of the knockout mouse and the related technology of gene targeting, a method of using embryonic stem cells to create specific gene modifications in mice. In 2007, the three shared the Nobel Prize in Physiology or Medicine in recognition of their discovery and contribution to the efforts to develop new treatments for illnesses in humans.

Hans Grüneberg British geneticist

Hans Grüneberg, whose name was also written as Hans Grueneberg and Hans Gruneberg, was a British geneticist. Grüneberg was born in Wuppertal–Elberfeld in Germany. He obtained an MD from the University of Bonn, a PhD in biology from the University of Berlin and a DSc from the University of London. He arrived in London in 1933, at the invitation of J.B.S. Haldane and Sir Henry Dale.

Salome Gluecksohn-Waelsch was a German-born U.S. geneticist and co-founder of the field of developmental genetics, which investigates the genetic mechanisms of development.

Sex chromosome A chromosome involved in sex determination.

An allosome is a chromosome that differs from an ordinary autosome in form, size, and behavior. The human sex chromosomes, a typical pair of mammal allosomes, determine the sex of an individual created in sexual reproduction. Autosomes differ from allosomes because autosomes appear in pairs whose members have the same form but differ from other pairs in a diploid cell, whereas members of an allosome pair may differ from one another and thereby determine sex.

ABCD1 protein-coding gene in the species Homo sapiens

ABCD1 is a protein that transfers fatty acids into peroxisomes.

ARID2 protein-coding gene in the species Homo sapiens

AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.

POU3F4 protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome.

Gail R. Martin American biologist

Gail Roberta Martin is a professor emerita in the Department of Anatomy, University of California, San Francisco. She is known for her pioneering work on the isolation of pluripotent stem cells from normal embryos, for which she coined the term ‘embryonic stem cells’. She is also widely recognized for her work on the function of Fibroblast Growth Factors (FGFs) and their negative regulators in vertebrate organogenesis. She and her colleagues also made valuable contributions to gene targeting technology.

Patricia Ann Jacobs OBE FRSE FRS FMedSci FRCPath is a Scottish geneticist and is Honorary Professor of Human Genetics, Co-director of Research, Wessex Regional Genetics Laboratory, within the University of Southampton.

A knockout mouse or knock-out mouse is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.

Tsix non-coding RNA in the species Homo sapiens

Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.

Mutagenesis in the laboratory is an important technique whereby DNA mutations are deliberately engineered to produce mutant genes, proteins, strains of bacteria, or other genetically modified organisms. Various constituents of a gene, such as its control elements and its gene product, may be mutated so that the functioning of a gene or protein can be examined in detail. The mutation may also produce mutant proteins with interesting properties, or enhanced or novel functions that may be of commercial use. Mutant strains may also be produced that have practical application or allow the molecular basis of particular cell function to be investigated.

Elizabeth (Liz) Jane Robertson FRS is a British developmental biologist based at the Sir William Dunn School of Pathology, University of Oxford. She is Professor of Developmental Biology at Oxford and a Wellcome Trust Principal Research Fellow. She is best known for her pioneering work in developmental genetics, showing that genetic mutations could be introduced into the mouse germ line by using genetically altered embryonic stem cells. This discovery opened up a major field of experimentation for biologists and clinicians.

Lawrence B. Salkoff

Lawrence B. Salkoff is an American neuroscientist and currently a professor of Neuroscience and Genetics at Washington University School of Medicine

Stephen D. M. Brown Director, MRC Mammalian Genetics Unit, MRC Harwell

Steve David Macleod Brown FRS FMedSci is director of the Medical Research Council (MRC) Mammalian Genetics Unit, MRC Harwell at Harwell Science and Innovation Campus, Oxfordshire, a research centre on mouse genetics. In addition, he is the head of the Genetics and Pathobiology of Deafness research group there.

Jeannie T. Lee is a Professor of Genetics and Pathology at Harvard Medical School and the Massachusetts General Hospital, and a Howard Hughes Medical Institute Investigator. She is known for her work on X-chromosome inactivation and for discovering the functions of a new class of epigenetic regulators known as long noncoding RNAs (lncRNAs) for example Xist and Tsix.

Carolyn J. Brown is a Canadian geneticist and Professor in the Department of Medical Genetics at the University of British Columbia. Brown is renowned for her studies on X-chromosome inactivation, having discovered the human XIST gene in 1990.

References

  1. 1 2 Anon (2015). Lyon, Mary Frances. ukwhoswho.com. Who's Who (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. doi:10.1093/ww/9780199540884.013.U25200. Closed Access logo alternative.svg (subscription required)
  2. Lyon, M. F. (1998). "X-chromosome inactivation: A repeat hypothesis". Cytogenetics and Cell Genetics. 80 (1–4): 133–7. doi:10.1159/000014969. PMID   9678347.
  3. 1 2 3 4 5 "EC/1973/19: Lyon, Mary Frances". London: The Royal Society. Archived from the original on 7 February 2015.
  4. "Mary Lyon, geneticist – obituary". The Daily Telegraph . 3 February 2015. Retrieved 4 March 2015.
  5. Rastan, Sohaila (2015). "Mary F. Lyon (1925–2014) Grande dame of mouse genetics". Nature. 518 (7537): 36. doi:10.1038/518036a. PMID   25652989.
  6. "Formal portrait of Mary Lyon by Godfrey Argent". London: The Royal Society. Archived from the original on 7 February 2015.
  7. Mary Lyon Entry in Who named it?. Retrieved 4 March 2015.
  8. Oakes, Elizabeth H. Lyon, Mary Frances. International Encyclopedia of Women Scientists. New York, NY. Facts on File, Inc. 2002. Facts on File, Inc. Science Online. factsonfile.com.
  9. Lyon, M. F. (1961). "Gene action in the X-chromosome of the mouse (Mus musculus L.)". Nature. 190 (4773): 372–3. Bibcode:1961Natur.190..372L. doi:10.1038/190372a0. PMID   13764598.
  10. Brockdorff, Neil (2017). "Polycomb complexes in X chromosome inactivation". Philosophical Transactions of the Royal Society B . 372 (1733): 20170021. doi:10.1098/rstb.2017.0021. ISSN   0962-8436. PMC   5627167 . PMID   28947664.
  11. Heard, Edith; Brockdorff, Neil (2017). "Preface: X-chromosome inactivation and Mary Lyon". Philosophical Transactions of the Royal Society B . 372 (1733): 20160353. doi:10.1098/rstb.2016.0353. ISSN   0962-8436. PMC   5627156 . PMID   28947653. Open Access logo PLoS transparent.svg
  12. "Genetics and Medicine Historical Network".
  13. 1 2 3 4 Gitschier, J. (2010). "The Gift of Observation: An Interview with Mary Lyon". PLoS Genetics. 6 (1): e1000813. doi:10.1371/journal.pgen.1000813. PMC   2809768 . PMID   20107603.
  14. 1 2 Peter Harper (11 October 2004). "Mary Lyon". Genetics and Medicine Historical Network, Cardiff University.
  15. Haines, Catharine M. C. (2018). 1. doi:10.1093/odnb/9780198614128.013.109090.Missing or empty |title= (help)
  16. Mary F. Lyon's publications indexed by the Scopus bibliographic database. (subscription required)
  17. Lyon, M. F. (1986). "Male sterility of the mouse t-complex is due to homozygosity of the distorter genes". Cell. 44 (2): 357–363. doi:10.1016/0092-8674(86)90770-1.
  18. Lyon, M. F. (1972). "X-Chromosome Inactivation and Developmental Patterns in Mammals". Biological Reviews. 47 (1): 1–35. doi:10.1111/j.1469-185X.1972.tb00969.x. PMID   4554151.
  19. Puck, J. M.; Willard, H. F. (1998). "X inactivation in females with X-linked disease". New England Journal of Medicine. 338 (5): 325–8. doi:10.1056/NEJM199801293380611. PMID   9445416.
  20. Lyon, M. F. (1962). "Sex chromatin and gene action in the mammalian X-chromosome". American Journal of Human Genetics. 14: 135–48. PMC   1932279 . PMID   14467629.