Margaret Oakley Dayhoff
Encyclopedia
Dr. Margaret Belle Dayhoff (March 11, 1925 – February 5, 1983) was an American physical chemist and a pioneer in the field of bioinformatics
. Dayhoff was a professor at Georgetown University Medical Center
and a noted research biochemist at the National Biomedical Research Foundation where she pioneered the application of mathematics and computational methods to the field of biochemistry. She dedicated her career to applying the evolving computational technologies to support advances in biology and medicine, most notably the creation of protein and nucleic acid databases and tools to interrogate the databases. Her PhD degree was from Columbia University
in the Department of Chemistry, where she devised computational methods to calculate molecular resonance energies of several organic compounds. She did postdoctoral studies at the Rockefeller Institute (now Rockefeller University
) and the University of Maryland
, and joined the newly established National Biomedical Research Foundation in 1959. She was the first woman to hold office in the Biophysical Society
, first as Secretary and eventually President. She originated one of the first substitution matrices
, Point accepted mutation
s (PAM). The one-letter code
used for amino acids was developed by her, reflecting an attempt to reduce the size of the data files used to describe amino acid sequences in an era of punch-card computing.
as a child. Her academic promise was evident from the outset; she was valedictorian (class of 1942) at Bayside High School, Bayside, New York and from there received a scholarship to Washington Square College of New York University
, graduating magna cum laude in mathematics
in 1945.
Department of Chemistry. In her graduate thesis, Dayhoff had pioneered the use of computer capabilities — i.e., mass-data processing — to theoretical chemistry; specifically, she applied punch card machines to calculate the resonance energies
of several polycyclic
organic molecules.
After completing her Ph.D, Dayhoff studied electrochemistry
at the Rockefeller Institute from 1948 to 1951. In 1952, she moved to Maryland with her family and later received a research fellowship from the University of Maryland (1957–1959), working on a model of chemical bonding with Ellis Lippincott. She taught physiology and biophysics for 13 years, while becoming affiliated with the National Biomedical Research Foundation, a Fellow of the American Association for the Advancement of Science
, a councillor of the International Society for the Study of the Origins of Life (1980) and acting on the editorial boards of DNA, Journal of Molecular Evolution
and Computers in Biology and Medicine
.
Frederic Sanger's determination of the first complete amino acid sequence of a protein (insulin) in 1955, led a number of researchers to sequence various proteins from different species. In the early 1960s, a theory was developed that small differences between homologous protein sequences (sequences with a high likelihood of common ancestry) could indicate the process and rate of evolutionary change on the molecular level. The notion that such molecular analysis could help scientists decode evolutionary patterns in organisms was formalized in the published papers of Emile Zuckerkandl
and Linus Pauling
in 1962 and 1965. Dayhoff worked side by side with Lippincott and Carl Sagan
on thermodynamic models of cosmo-chemical systems, including prebiological planetary atmospheres.
Dayhoff went on to pioneer the development of programmable computer methods for use in comparing protein sequences and deriving their evolutionary histories (in other words, discerning homologies) from their sequence alignment
s. Though this was before the days of massive outputs of sequence information by automated and other methods, Margaret Dayhoff anticipated the potential of computers to the current theories of Zuckerkandl
& Pauling
and the method which Sanger had engineered.
With Richard Eck, she published the first reconstruction of a phylogeny (evolutionary tree) by computers from molecular sequences, using a maximum parsimony
method. She also formulated the first probability model of protein evolution, the PAM
model, in 1966.
She initiated the collection of protein sequences in the Atlas of Protein Sequence and Structure, a book collecting all known protein sequences that she published in 1965. It was subsequently republished in several editions. This led to the Protein Information Resource
database of protein sequences, which was developed by her group. It and the parallel effort by Walter Goad
which led to the GenBank
database of nucleic acid sequences are the twin origins of the modern databases of molecular sequences. The Atlas was organized by gene families
, and she is regarded as a pioneer in their recognition. Her approach to proteins was always determinedly evolutionary. Margaret Oakley Dayoff died of a heart attack at the age of 57.
David Lipman has called Dayhoff the mother and father of bioinformatics. Lipman, who is director of the National Center for Biotechnology Information
is also the scientist who spearheaded the collaborative project that produced BLAST
. His ongoing work in developing better computational methods for molecular biology attests to his inheritance of Dayhoff’s legacy.
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
. Dayhoff was a professor at Georgetown University Medical Center
Georgetown University Medical Center
Georgetown University Medical Center is the medical campus at Georgetown University. It is also a $225 million biomedical research and educational organization. The Medical Center contains over 80% of Georgetown University's sponsored research funding and is led by Howard J...
and a noted research biochemist at the National Biomedical Research Foundation where she pioneered the application of mathematics and computational methods to the field of biochemistry. She dedicated her career to applying the evolving computational technologies to support advances in biology and medicine, most notably the creation of protein and nucleic acid databases and tools to interrogate the databases. Her PhD degree was from Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
in the Department of Chemistry, where she devised computational methods to calculate molecular resonance energies of several organic compounds. She did postdoctoral studies at the Rockefeller Institute (now Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...
) and the University of Maryland
University of Maryland
When the term "University of Maryland" is used without any qualification, it generally refers to the University of Maryland, College Park.University of Maryland may refer to the following:...
, and joined the newly established National Biomedical Research Foundation in 1959. She was the first woman to hold office in the Biophysical Society
Biophysical Society
The Biophysical Society is an organization consisting of over 9,000 researchers in academia, government, and industry. Based in the USA, its international membership has grown to about 1/3 of the total. Founded in 1957 by Ernest C...
, first as Secretary and eventually President. She originated one of the first substitution matrices
Substitution matrix
In bioinformatics and evolutionary biology, a substitution matrix describes the rate at which one character in a sequence changes to other character states over time...
, Point accepted mutation
Point accepted mutation
Point accepted mutation , is a set of matrices used to score sequence alignments. The PAM matrices were introduced by Margaret Dayhoff in 1978 based on 1572 observed mutations in 71 families of closely related proteins...
s (PAM). The one-letter code
Proteinogenic amino acid
Proteinogenic amino acids are those amino acids that can be found in proteins and require cellular machinery coded for in the genetic code of any organism for their isolated production. There are 22 standard amino acids, but only 21 are found in eukaryotes. Of the 22, 20 are directly encoded by...
used for amino acids was developed by her, reflecting an attempt to reduce the size of the data files used to describe amino acid sequences in an era of punch-card computing.
Early life
Dayhoff was born an only child in Philadelphia, but moved to New York CityNew York City
New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
as a child. Her academic promise was evident from the outset; she was valedictorian (class of 1942) at Bayside High School, Bayside, New York and from there received a scholarship to Washington Square College of New York University
New York University
New York University is a private, nonsectarian research university based in New York City. NYU's main campus is situated in the Greenwich Village section of Manhattan...
, graduating magna cum laude in mathematics
Mathematics
Mathematics is the study of quantity, space, structure, and change. Mathematicians seek out patterns and formulate new conjectures. Mathematicians resolve the truth or falsity of conjectures by mathematical proofs, which are arguments sufficient to convince other mathematicians of their validity...
in 1945.
Research
From there, Dayhoff undertook a Ph.D. in quantum chemistry, under George Kimball, in the Columbia UniversityColumbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
Department of Chemistry. In her graduate thesis, Dayhoff had pioneered the use of computer capabilities — i.e., mass-data processing — to theoretical chemistry; specifically, she applied punch card machines to calculate the resonance energies
Resonance
In physics, resonance is the tendency of a system to oscillate at a greater amplitude at some frequencies than at others. These are known as the system's resonant frequencies...
of several polycyclic
Polycyclic compound
In organic chemistry, a polycyclic compound is a cyclic compound with more than one hydrocarbon loop or ring structures . In general, the term includes all polycyclic aromatic compounds, including the polycyclic aromatic hydrocarbons, the heterocyclic aromatic compounds containing sulfur,...
organic molecules.
After completing her Ph.D, Dayhoff studied electrochemistry
Electrochemistry
Electrochemistry is a branch of chemistry that studies chemical reactions which take place in a solution at the interface of an electron conductor and an ionic conductor , and which involve electron transfer between the electrode and the electrolyte or species in solution.If a chemical reaction is...
at the Rockefeller Institute from 1948 to 1951. In 1952, she moved to Maryland with her family and later received a research fellowship from the University of Maryland (1957–1959), working on a model of chemical bonding with Ellis Lippincott. She taught physiology and biophysics for 13 years, while becoming affiliated with the National Biomedical Research Foundation, a Fellow of the American Association for the Advancement of Science
American Association for the Advancement of Science
The American Association for the Advancement of Science is an international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsibility, and supporting scientific education and science outreach for the...
, a councillor of the International Society for the Study of the Origins of Life (1980) and acting on the editorial boards of DNA, Journal of Molecular Evolution
Journal of Molecular Evolution
The Journal of Molecular Evolution is a peer-reviewed scientific journal that covers molecular evolution. The journal is published by Springer and was established in 1971. The founding editor is Emile Zuckerkandl, who remained editor in chief until the late 1990s...
and Computers in Biology and Medicine
Computers in Biology and Medicine
Computers in Biology and Medicine is a peer-reviewed scientific journal founded in 1970. It covers the intersection of biology, medical informatics, bioinformatics, and medicine....
.
Frederic Sanger's determination of the first complete amino acid sequence of a protein (insulin) in 1955, led a number of researchers to sequence various proteins from different species. In the early 1960s, a theory was developed that small differences between homologous protein sequences (sequences with a high likelihood of common ancestry) could indicate the process and rate of evolutionary change on the molecular level. The notion that such molecular analysis could help scientists decode evolutionary patterns in organisms was formalized in the published papers of Emile Zuckerkandl
Emile Zuckerkandl
Emile Zuckerkandl is an Austrian-American biologist considered one of the founders of the field of molecular evolution. He is best known for introducing, with Linus Pauling, the concept of the molecular clock, which set the stage for the neutral theory of molecular evolution.- Life and work...
and Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
in 1962 and 1965. Dayhoff worked side by side with Lippincott and Carl Sagan
Carl Sagan
Carl Edward Sagan was an American astronomer, astrophysicist, cosmologist, author, science popularizer and science communicator in astronomy and natural sciences. He published more than 600 scientific papers and articles and was author, co-author or editor of more than 20 books...
on thermodynamic models of cosmo-chemical systems, including prebiological planetary atmospheres.
Dayhoff went on to pioneer the development of programmable computer methods for use in comparing protein sequences and deriving their evolutionary histories (in other words, discerning homologies) from their sequence alignment
Sequence alignment
In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Aligned sequences of nucleotide or amino acid residues are...
s. Though this was before the days of massive outputs of sequence information by automated and other methods, Margaret Dayhoff anticipated the potential of computers to the current theories of Zuckerkandl
Emile Zuckerkandl
Emile Zuckerkandl is an Austrian-American biologist considered one of the founders of the field of molecular evolution. He is best known for introducing, with Linus Pauling, the concept of the molecular clock, which set the stage for the neutral theory of molecular evolution.- Life and work...
& Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
and the method which Sanger had engineered.
With Richard Eck, she published the first reconstruction of a phylogeny (evolutionary tree) by computers from molecular sequences, using a maximum parsimony
Maximum parsimony
Parsimony is a non-parametric statistical method commonly used in computational phylogenetics for estimating phylogenies. Under parsimony, the preferred phylogenetic tree is the tree that requires the least evolutionary change to explain some observed data....
method. She also formulated the first probability model of protein evolution, the PAM
Point accepted mutation
Point accepted mutation , is a set of matrices used to score sequence alignments. The PAM matrices were introduced by Margaret Dayhoff in 1978 based on 1572 observed mutations in 71 families of closely related proteins...
model, in 1966.
She initiated the collection of protein sequences in the Atlas of Protein Sequence and Structure, a book collecting all known protein sequences that she published in 1965. It was subsequently republished in several editions. This led to the Protein Information Resource
Protein Information Resource
The Protein Information Resource , located at Georgetown University Medical Center , is an integrated public bioinformatics resource to support genomic and proteomic research, and scientific studies-History:...
database of protein sequences, which was developed by her group. It and the parallel effort by Walter Goad
Walter Goad
Walter Goad is one of the founders of GenBank when he was in Los Alamos. He was born in 1925 and died in 2000. From 1970 to 1971, he worked with Francis Crick at the MRC LMB of Cambridge.-References:****-External links:...
which led to the GenBank
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. This database is produced and maintained by the National Center for Biotechnology Information as part of the International Nucleotide Sequence...
database of nucleic acid sequences are the twin origins of the modern databases of molecular sequences. The Atlas was organized by gene families
Gene family
A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions...
, and she is regarded as a pioneer in their recognition. Her approach to proteins was always determinedly evolutionary. Margaret Oakley Dayoff died of a heart attack at the age of 57.
David Lipman has called Dayhoff the mother and father of bioinformatics. Lipman, who is director of the National Center for Biotechnology Information
National Center for Biotechnology Information
The National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
is also the scientist who spearheaded the collaborative project that produced BLAST
BLAST
In bioinformatics, Basic Local Alignment Search Tool, or BLAST, is an algorithm for comparing primary biological sequence information, such as the amino-acid sequences of different proteins or the nucleotides of DNA sequences...
. His ongoing work in developing better computational methods for molecular biology attests to his inheritance of Dayhoff’s legacy.
External links
- Dr. Margaret Oakley Dayhoff — Pioneer in Bioinformatics
- Picture of Margaret Oakley Dayhoff, c. 1980. Owned by her daughter Ruth E. Dayhoff, M.D. Made available by the National Library of Medicine.