Mary F. Lyon

This article is about the 20th century British geneticist. For the 19th century American educator, see Mary Lyon.
Mary F. Lyon
Born Mary Frances Lyon
(1925-05-15)15 May 1925[1]
Norwich, England
Died 25 December 2014(2014-12-25) (aged 89)
Alma mater University of Cambridge (BA, PhD)
Doctoral advisor Ronald Fisher
Doctoral students Sohaila Rastan, Elizabeth Fisher (co-supervised with Steve Brown)
Known for X-chromosome inactivation[2]
Notable awards

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

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[10] and nature books she won in an essay competition.[11] During the second world war, she pursued her studies at Girton College, Cambridge at the University of Cambridge,[12] 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.[11] 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 characterized a mutant mice strain with a 'pallid' mutation and published the research. During the course of her PhD she moved to Edinburgh.

Research

After her PhD Mary 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).

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 scrutinized 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.[11]

Lyon published many peer-reviewed papers on radiation and chemical mutagenesis and on studies of mutant genes.[13] name She also did extensive work on the mouse t-complex,.[14][15]

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.[11]

X-inactivation

It was while working on radiation hazards in 1961 that she discovered X-chromosome inactivation, for which she is best known,[12] 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.[16]

Awards and honours

Mary Frances Lyon was elected a Fellow of the Royal Society in 1973,[3] a Foreign Associate of the U.S. 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.[17] 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:

Distinguished for many important contributions to mammalian genetics, notably on the mutagenic effects of irradiation as measured in mice, and on the building of the hypothesis that one of the two X chromosomes of the female is inactivated at an early stage of embryogenesis. The hypothesis, which is now almost universally accepted as proved, offered a solution to the long standing problem of X-dosage compensation in the female mammal, has thrown much light on the nature of sex-chromosome aneuploidy, has influenced ideas on the origin of certain tumours and of chronic granulocytic leukaemia in man, and has provided food for thought about the fundamental mechanism of switching off genes. Lyonisation, as others were quick to call the phenomenon, has perhaps opened more lines of enquiry and stimulated more work than any recent biological concept.[3]

References

  1. 1 2 LYON, Mary Frances. Who's Who. 2015 (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. (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 2015-02-07.
  4. "Mary Lyon, geneticist - obituary". 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 2015-02-07.
  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: 372–3. doi:10.1038/190372a0. PMID 13764598.
  10. http://www.genmedhist.info/interviews/Lyon
  11. 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 2809768Freely accessible. PMID 20107603.
  12. 1 2 Peter Harper (11 October 2004). "Mary Lyon". Genetics and Medicine Historical Network, Cardiff University.
  13. Mary F. Lyon's publications indexed by the Scopus bibliographic database, a service provided by Elsevier. (subscription required)
  14. 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.
  15. Lyon, M. F. (1972). "X-Chromosome Inactivation and Developmental Patterns in Mammals". Biological Reviews. 47: 1–35. doi:10.1111/j.1469-185X.1972.tb00969.x.
  16. 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.
  17. Lyon, M. F. (1962). "Sex chromatin and gene action in the mammalian X-chromosome". American Journal of Human Genetics. 14: 135–48. PMC 1932279Freely accessible. PMID 14467629.
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