Molecular Structure of Nucleic Acids A Structure for Deoxyribose Nucleic Acid - Wikipedia

3/12/2021
Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid - Wikipedia
Molecular Structure of Nucleic Acids: A Structure for
Deoxyribose Nucleic Acid
"Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid" was the first
article published to describe the discovery of the double helix structure of DNA, using X-ray
diffraction and the mathematics of a helix transform. It was published by Francis Crick and James D.
Watson in the scientific journal Nature on pages 737–738 of its 171st volume (dated 25 April
1953).[1][2]
Diagramatic representation of the key
structural features of the DNA double
helix. This figure does not depict BDNA.
This article is often termed a "pearl" of science because it is brief and contains the answer to a
fundamental mystery about living organisms. This mystery was the question of how it is possible
that genetic instructions are held inside organisms and how they are passed from generation to
generation. The article presents a simple and elegant solution, which surprised many biologists at
the time who believed that DNA transmission was going to be more difficult to deduce and
understand. The discovery had a major impact on biology, particularly in the field of genetics,
enabling later researchers to understand the genetic code.
Evolution of molecular biology
The application of physics and chemistry to biological problems led to the development of
molecular biology, which is particularly concerned with the flow and consequences of biological
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information from DNA to proteins. The discovery of the DNA double helix made clear that genes are
functionally defined parts of DNA molecules, and that there must be a way for cells to translate the
information in DNA to specific amino acids, which are used in order to make proteins.
Linus Pauling was a chemist who was very influential in developing an understanding of the
structure of biological molecules. In 1951, Pauling published the structure of the alpha helix, a
fundamentally important structural component of proteins. In early 1953, Pauling published a triple
helix model of DNA, which subsequently turned out to be incorrect.[3] Both Crick, and particularly
Watson, thought that they were racing against Pauling to discover the structure of DNA.
Max Delbrück was a physicist who recognized some of the biological implications of quantum
physics. Delbruck's thinking about the physical basis of life stimulated Erwin Schrödinger to write,
What Is Life? Schrödinger's book was an important influence on Crick and Watson. Delbruck's efforts
to promote the "Phage Group" (exploring genetics by way of the viruses that infect bacteria) was
important in the early development of molecular biology in general and the development of
Watson's scientific interests in particular.[4]
Crick, Watson, and Maurice Wilkins who won the Nobel Prize for Medicine in recognition of their
discovery of the DNA double helix.
DNA structure and function
It is not always the case that the structure of a molecule is easy to relate to its function. What makes
the structure of DNA so obviously related to its function was described modestly at the end of the
article: "It has not escaped our notice that the specific pairing we have postulated immediately
suggests a possible copying mechanism for the genetic material".
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DNA replication. The two base-pair
complementary chains of the DNA
molecule allow replication of the
genetic instructions.
The "specific pairing" is a key feature of the Watson and Crick model of DNA, the pairing of
nucleotide subunits.[5] In DNA, the amount of guanine is equal to cytosine and the amount of
adenine is equal to thymine. The A:T and C:G pairs are structurally similar. In particular, the length of
each base pair is the same and they fit equally between the two sugar-phosphate backbones. The
base pairs are held together by hydrogen bonds, a type of chemical attraction that is easy to break
and easy to reform. After realizing the structural similarity of the A:T and C:G pairs, Watson and Crick
soon produced their double helix model of DNA with the hydrogen bonds at the core of the helix
providing a way to unzip the two complementary strands for easy replication: the last key
requirement for a likely model of the genetic molecule.
Indeed, the base-pairing did suggest a way to copy a DNA molecule. Just pull apart the two sugarphosphate backbones, each with its hydrogen bonded A, T, G, and C components. Each strand could
then be used as a template for assembly of a new base-pair complementary strand.
Future considerations
…
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Watson and Crick used many
aluminium templates like this one,
which is the single base Adenine (A),
to build a physical model of DNA in
1953.
When Watson and Crick produced their double helix model of DNA, it was known that most of the
specialized features of the many different life forms on Earth are made possible by proteins.
Structurally, proteins are long chains of amino acid subunits. In some way, the genetic molecule,
DNA, had to contain instructions for how to make the thousands of proteins found in cells. From the
DNA double helix model, it was clear that there must be some correspondence between the linear
sequences of nucleotides in DNA molecules to the linear sequences of amino acids in proteins. The
details of how sequences of DNA instruct cells to make specific proteins was worked out by
molecular biologists during the period from 1953 to 1965. Francis Crick played an integral role in
both the theory and analysis of the experiments that led to an improved understanding of the
genetic code.[6]
Consequences
…
Other advances in molecular biology stemming from the discovery of the DNA double helix
eventually led to ways to sequence genes. James Watson directed the Human Genome Project at
the National Institutes of Health.[7] The ability to sequence and manipulate DNA is now central to
the biotechnology industry and modern medicine. The austere beauty of the structure and the
practical implications of the DNA double helix combined to make Molecular structure of Nucleic
Acids; A Structure for Deoxyribose Nucleic Acid one of the most prominent biology articles of the
twentieth century.
Collaborators and controversy
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Although Watson and Crick were first to put together all the scattered fragments of information that
were required to produce a successful molecular model of DNA, their findings had been based on
data collected by researchers in several other laboratories. For example they drew on published
research relating to the discovery of Hydrogen bonds in DNA by John Masson Gulland, Denis Jordan
and their colleagues at University College Nottingham in 1947.[8][9][10] However the discovery of the
DNA double helix also used a considerable amount of material from the unpublished work of
Rosalind Franklin, A.R. Stokes, Maurice Wilkins, and H.R. Wilson at King's College London. Key data
from Wilkins, Stokes, and Wilson, and, separately, by Franklin and Gosling, were published in two
separate additional articles in the same issue of Nature with the article by Watson and Crick.[11][12]
The article by Watson and Crick acknowledged that they had been "stimulated" by experimental
results from the King's College researchers, and a similar acknowledgment was published by Wilkins,
Stokes, and Wilson in the following three-page article.
In 1968, Watson published a highly controversial autobiographical account of the discovery of the
double-helical, molecular structure of DNA called The Double Helix, which was not publicly accepted
either by Crick or Wilkins.[13] Furthermore, Erwin Chargaff also printed a rather "unsympathetic
review" of Watson's book in the March 29, 1968 issue of Science. In the book, Watson stated among
other things that he and Crick had access to some of Franklin's data from a source that she was not
aware of, and also that he had seen—without her permission—the B-DNA X-ray diffraction pattern
obtained by Franklin and Gosling in May 1952 at King's in London. In particular, in late 1952,
Franklin had submitted a progress report to the Medical Research Council, which was reviewed by
Max Perutz, then at the Cavendish Laboratory of the University of Cambridge. Watson and Crick also
worked in the MRC-supported Cavendish Laboratory in Cambridge whereas Wilkins and Franklin
were in the MRC-supported laboratory at King's in London. Such MRC reports were not usually
widely circulated, but Crick read a copy of Franklin's research summary in early 1953.[13][14]
Perutz's justification for passing Franklin's report about the crystallographic unit of the B-DNA and
A-DNA structures to both Crick and Watson was that the report contained information which
Watson had heard before, in November 1951, when Franklin talked about her unpublished results
with Raymond Gosling during a meeting arranged by M.H.F. Wilkins at King's College, following a
request from Crick and Watson;[15] Perutz said he had not acted unethically because the report had
been part of an effort to promote wider contact between different MRC research groups and was
not confidential.[16] This justification would exclude Crick, who was not present at the November
1951 meeting, yet Perutz also gave him access to Franklin's MRC report data. Crick and Watson then
sought permission from Cavendish Laboratory head William Lawrence Bragg, to publish their
double-helix molecular model of DNA based on data from Franklin and Wilkins.
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By November 1951, Watson had acquired little training in X-ray crystallography, by his own
admission, and thus had not fully understood what Franklin was saying about the structural
symmetry of the DNA molecule.[14] Crick, however, knowing the Fourier transforms of Bessel
functions that represent the X-ray diffraction patterns of helical structures of atoms, correctly
interpreted further one of Franklin's experimental findings as indicating that DNA was most likely to
be a double helix with the two polynucleotide chains running in opposite directions. Crick was thus
in a unique position to make this interpretation because he had formerly worked on the X-ray
diffraction data for other large molecules that had helical symmetry similar to that of DNA. Franklin,
on the other hand, rejected the first molecular model building approach proposed by Crick and
Watson: the first DNA model, which in 1952 Watson presented to her and to Wilkins in London, had
an obviously incorrect structure with hydrated charged groups on the inside of the model, rather
than on the outside. Watson explicitly admitted this in his book The Double Helix.[14]
See also
Comparison of nucleic acid simulation software: nucleic acid modeling
Crystallography
DNA
Miles from Tomorrowland, a TV series with twin admirals named Watson and Crick
Paracrystal model and theory
X-ray scattering
Keto-enol_tautomerism#DNA the final key insight, from a Pauling collaborator, that the textbooks
of the time were wrong, that led to the solved structure
Avery-MacLeod-McCarty experiment the first demonstration that DNA was likely to be the genetic
material
Chargraff's rule which showed that A:T and G:C occurred in equal amounts
References
1. Watson JD, Crick FH (April 1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic
acid"
(PDF). Nature. 171 (4356): 737–738. Bibcode:1953Natur.171..737W . doi:10.1038/171737a0 .
PMID 13054692 .
2. Cochran W, Crick FHC and Vand V. (1952) "The Structure of Synthetic Polypeptides. I. The Transform of
Atoms on a Helix", Acta Crystallogr., 5, 581–586.
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3. Pauling L, Corey RB (1953). "A Proposed Structure for the Nucleic Acids" . PNAS. 39 (2): 84–97.
Bibcode:1953PNAS...39...84P . doi:10.1073/pnas.39.2.84 . PMC 1063734 . PMID 16578429 .
4. Judson, Horace Freeland (1979). Eighth Day of Creation: Makers of the Revolution in Biology . New York:
Simon & Schuster. ISBN 9780671254100.
5. Discover the rules of DNA base pairing with an online simulator .
6. Perutz MF, Randall JT, Thomson L, Wilkins MH, Watson JD (June 1969). "DNA helix" . Science. 164 (3887):
1537–9. Bibcode:1969Sci...164.1537W . doi:10.1126/science.164.3887.1537 . PMID 5796048 .
7. "History - Historic Figures: Watson and Crick (1928- )" . BBC. Retrieved 15 June 2014.
8. JM Gulland; DO Jordan; HF Taylor; (1947) Deoxypentose nucleic acids; Part II electrometric titration of the
acidic and the basic groups of the deoxypentose nucleic acid of calf thymus. J Chem Soc. 1947; 25:113141.
9. Creeth, J.M., Gulland, J.M. and Jordan, D.O. (1947) Deoxypentose nucleic acids. Part III. Viscosity and
streaming birefringence of solutions of the sodium salt of the deoxypentose nucleic acid of calf thymus. J.
Chem. Soc. 1947,25 1141–1145
10. Watson, James D., 2012 The Annotated and Illustrated Double Helix, Ed. Gann & Witkowski, Simon &
Schuster, New York (pp196-7)
11. Franklin R, Gosling RG (25 April 1953). "Molecular configuration in sodium thymonucleate"
(PDF). Nature.
171 (4356): 740–741. Bibcode:1953Natur.171..740F . doi:10.1038/171740a0 . PMID 13054694 .
12. Wilkins MH, Stokes AR, Wilson HR (25 April 1953). "Molecular structure of deoxypentose nucleic acids"
(PDF). Nature. 171 (4356): 738–740. Bibcode:1953Natur.171..738W . doi:10.1038/171738a0 .
PMID 13054693 .
13. Beckwith, Jon (2003). "Double Take on the Double Helix" . In Victor K. McElheny (ed.). Watson and DNA:
Making a Scientific Revolution . Cambridge, MA: Perseus Publishing. p. 363 . ISBN 978-0-738-20341-6.
OCLC 51440191 .
14. Watson, James D. (1980). The Double Helix: A Personal Account of the Discovery of the Structure of DNA.
Atheneum. ISBN 978-0-689-70602-8. (first published in 1968)
15. Sayre, Anne (1975). Rosalind Franklin and DNA . New York: Norton.
16. Perutz MF, Randall JT, Thomson L, Wilkins MH, Watson JD (27 June 1969). "DNA helix" . Science. 164
(3887): 1537–1539. Bibcode:1969Sci...164.1537W . doi:10.1126/science.164.3887.1537 .
PMID 5796048 .
Bibliography
Judson, Horace Freeland (1979). The Eighth Day of Creation. Makers of the Revolution in Biology .
Simon and Schuster. ISBN 978-0-671-22540-7.
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Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid - Wikipedia
Maddox, Brenda (2002). Rosalind Franklin: The Dark Lady of DNA . ISBN 978-0-060-98508-0.
Olby, Robert (1974). The Path to The Double Helix: Discovery of DNA. MacMillan. ISBN 978-0-48668117-7. (with foreword by Francis Crick; revised in 1994, with a 9-page postscript.)
Watson, James D. (1980). The Double Helix: A Personal Account of the Discovery of the Structure of
DNA. Atheneum. ISBN 978-0-689-70602-8. (first published in 1968)
Wilkins, Maurice (2003). The Third Man of the Double Helix: The Autobiography of Maurice Wilkins.
ISBN 978-0-198-60665-9.
Life Story (TV film) a BBC dramatization about the scientific race to discover the DNA double-helix.
External links
Scholia has a work profile for Molecular Structure of Nucleic Acids: A Structure for
Deoxyribose Nucleic Acid.
Annotated copy of the article
from San Francisco's Exploratorium
Access Excellence Classic Collection article on DNA structure .
Linus Pauling and the Race for DNA: A Documentary History
Online versions
…
Online version (Original text) at nature.com
National Library of Medicine's PDF copy
Commemorative HTML version
in the Francis Crick Documents Collection .
Am J Psychiatry 160:623-624, April 2003.
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