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
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 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 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.
Crick, Watson, and
DNA structure and function
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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".
The "specific pairing" is a key feature of the Watson and Crick model of DNA, the pairing of
Indeed, the base-pairing did suggest a way to copy a DNA molecule. Just pull apart the two sugar-phosphate 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
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
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
In 1968, Watson published a highly controversial autobiographical account of the discovery of the
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
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
- Miles from Tomorrowland, a TV series (2015–2018) with twin admirals named Watson and Crick
- Paracrystallinity
- 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
- Chargaff's rules, which showed that A:T and G:C occurred in equal amounts
References
- S2CID 4253007.
- ^ 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.
- PMID 16578429.
- ISBN 9780671254100.
- ^ Discover the rules of DNA base pairing with an online simulator.
- PMID 5796048.
- ^ "History – Historic Figures: Watson and Crick (1928- )". BBC. Retrieved 15 June 2014.
- ^ 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; 25:1131-41.
- ^ 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
- ^ Watson, James D., 2012 The Annotated and Illustrated Double Helix, Ed. Gann & Witkowski, Simon & Schuster, New York (pp196-7)
- S2CID 4268222.
- S2CID 4280080.
- ^ OCLC 51440191.
- ^ ISBN 978-0-689-70602-8. (first published in 1968)
- ^ Sayre, Anne (1975). Rosalind Franklin and DNA. New York: Norton.
- PMID 5796048.
Bibliography
- ISBN 978-0-671-22540-7.
- ISBN 978-0-060-98508-0.
- ISBN 978-0-486-68117-7. (with foreword by Francis Crick; revised in 1994, with a 9-page postscript.)
- Watson, James D. (1980). ISBN 978-0-689-70602-8. (first published in 1968)
- ISBN 978-0-198-60665-9.
- Life Story (TV film) a BBCdramatization about the scientific race to discover the DNA double-helix.
External links
- 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 in the Francis Crick Documents Collection.
- Commemorative HTML version Am J Psychiatry 160:623-624, April 2003.