8 minutes reading time (1605 words)

    DISCOVERY OF THE STRUCTURE OF THE DEOXYRIBONUCLEIC ACID (DNA) MOLECULE

     In 1968 a book was published in which a very personal account of the discovery of the structure of the DNA molecule was presented. It was a popular book aimed at a wide range of readers. The book was entitled "The Double Helix', and was written by James D. Watson, one of the participants in the discovery of a DNA model. It was published by Atheneum, New York. The book proved to be an instant success as it provided not only a fascinating insight into the most important biological discovery of this century but it also disclosed scientists' personal relationships, their reactions and feelings, as they proceeded toward the culmination of their work - the discovery of the structure of the DNA molecule.

    The "Double Helix" story starts in 1951, when coincidental events brought together two young scientists: an American biologist named James D. Watson, and an English physicist, Francis Crick. Watson worked in the laboratory of the known Harvard virologist Salvador Luria, and was interested in DNA. Francis Crick worked with Cambridge biochemist Max Perutz on the structure of the large biological molecules. They had met in Cambridge at the time when accumulating research data was providing interesting information about various properties and possible importance of DNA in the living cells. The facts available to these two young men at that time are presented below.

    Group of Facts 1

    Since the early forties DNA was implicated as a possible genetic material in living cells. The first conclusive experimental support came from the paper published in 1944 by O.T. Avery, C.M. Macleod and M. McCarty who reported that the DNA fraction isolated from the encapsulated form of bacterium named Pneumococcus pneumoniae was able to transform (change the genetic make-up) the form of pneumococcus pneumoniae devoided of the capsule. The result of the transformation by "foreign" DNA - the form of P. pneumoniae devoided of the capsule started to produce the capsule.
    These research data provided scientific evidence that a genetic make-up of living things could be changed if an additional fragment of DNA is introduced into the cell. It also strongly implicated that DNA serves as a bearer of genetic information.

    Group of Facts 2.

    In the fifties American virologists, Hershey and Chase (1952) provided further evidence that DNA, not proteins, contains the blueprints for manufacturing the new particles of T2 viruses in the T2-infected cells of bacteria. By their experiment Hershey and Chase confirmed the existence of the DNA genetic information bearing capacity in the living world. In their experiments they used micro-organisms different from those used by O.T. Avery and C.M. MacLeod - viruses instead of bacteria.
    Similarity in the results obtained by using viruses and bacteria in these experiments suggested a potential universality of the DNA blueprint among living things.

    Group of Facts 3.

    Furthermore, at that time it was known already from the work of various chemists that deoxyribonucleic acid (DNA) is a polymer molecule which consists of building blocks (smaller molecules). Such smaller molecules, in turn, comprise of 3 even smaller components: one of the four nitrogenous bases, sugar-deoxyribose and a phosphoric acid residue (PO43-). The nitrogenous bases could be of two types: purines and pyrimidines. Purines consist of two rings made of carbon and nitrogen molecules, while pyrimidines contain only one carbon-nitrogen ring. Later these bases were confirmed to be purines: adenine, guanine and pyrimidines: thymine and cytosine (Figure 1).

     The results of chemical analyses of DNA provided an insight into the structure of the building blocks of DNA and implied a possible polymeric structure of DNA molecules.


    Group of Facts 4.

    Biochemical studies performed by Alexander Todd and Linus Pauling on the structure of complex, biologically active molecules demonstrated high regularity and commonality of q-helix structure among them.
    These findings provided an indication of a possible solution for the structure of the polymeric DNA molecule.

    Group of Facts 5:

    Erwin Chargaff in 1950 added his contribution to the solution of the DNA puzzle by publishing the results of his chemical analysis concerning the base composition of DNA from various living organisms. He discovered that the DNAs from different species were characterised by specific proportions of four basic units (bases): purines (adenine and guanine) and pyrimidines (thymine and cytosine). What was even more remarkable the ratios of A:T and G:C were always close to one in tested species. It meant that the amounts of bases in pairs A-T and G-C were always found to be equal regardless of the source of a sample:

     The finding of Chargaff provided a strong indication of a possible pairing pattern of bases (A-T; G-C) in the molecules of DNA.

    Group of Facts 6:

    The last bits of evidence available to Watson and Crick came from the work of a young British scientist - Rosalind Franklin. She was working in Kings College, London, in the laboratory of the known crystallographer Maurice Wilks. While working there she obtained an X-ray photograph of a crystalline structure of a DNA molecule. (Figure 3). Her X-ray diffraction picture of DNA contained many black spots which represented shadows of the composite molecules that made up the polymer of DNA. The picture of DNA was surprisingly simple and symmetrical. The width of the DNA calculated from Rosalind's picture was about 2nm and it seemed too wide to consist on only one strand.

     The crystallographic work of Rosalind Franklin confirmed an orderly, symmetrical arrangement of molecules of DNA and postulated more than one strand structure of DNA polymers.

    The facts listed above were available to many other scientists, but only thanks to the fruitful cooperation of two young men, the ultimate discovery of the structure of DNA proved to be possible. J. Watson and F. Crick managed to put together the available facts and proposed a model of DNA perfect in its simplicity. In addition, the model could explain the process of the transmission of genetic information from one generation to another in a satisfactory way.

    They published two papers together in 1953:

    • Watson, J.D., Crick, F.H.C., 1953, Molecular Structure of Deoxyribonucleic Acid, Nature 171, 737-738.
    • Watson, J.D., Crick, F.H.C., 1953, Genetical Implication of the Structure of Deoxyribonucleic Acid, Nature 171, 964-967.

    In their papers they proposed (as described by Todoroska, E., 1991) that DNA consists of two complementary polymeric chains of nucleotides (Figure 4). They further reported that each nucleotide is made up of one of four bases, a molecule of a deoxyribose sugar and phosphoric acid residues. The chains of nucleotides are held together by phosphate linkages extending between the 5' and 3' carbon atoms of adjacent two sugar molecules. (Note: 5' and 3' - in chemical nomenclature indicates the position of the carbon atom of the sugar ring in relation to the atom labelled 1 that carries aldehyde group (C1); primes after the numbers indicate that the sugar ring is a side ring attached to the other main ring of the compound).

    In their model they postulated that sugar phosphate backbones of the two chains twist around each other to form the right-handed double helix with an outside diameter of 2nm. The backbone chains are separated from each other by a constant distance of approximately 1.1nm across the centre of the helix. This space is filled in by the base pairs. Each pair of bases consists of one purine and one pyrimidine base following the order of pairing A-T, G-C in agreement with Chargaff's chemical data. Specific hydrogen bonding between bases generates complementary base pairing and holds the helix together. There are three hydrogen bonds between G and C and two between A and T. The two chains of the Watson-Crick model are antiparalled. Their phosphate linkages in the left chain extend from the 5'- carbon of the sugar (deoxyribose) below to the 3'- carbon of the sugar above. In the right chain the phosphate linkages run in the opposite direction.

    Thus the chains are parallel, but run in opposite directions in a right-handed helix with about ten nucleotide pairs per one helical turn. Each helical turn is about 3.4nm long. (Figure 5).

    The limitation of a pairing pattern to A-T and G-C pairs in the two nucleotide chains suggested to Watson and Crick a possible basis for the exact duplication of DNA molecules, known to occur as a part of cell reproduction. To accommodate such a process the two chains separate and each makes a complementary copy of itself by forming the chain of matching base pairs (Figure 6). The result of duplication is two new double helices with a sequence of base pairs identical to that of the original double helix. Each contains one old and one newly synthesized chain.
    REFERENCES
    1. Avery, O.T., MacLeod, C.M., McCarty, M. 1944, "Studies on the Chemical Nature of the Substance Inducing Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III", J. Exp. Med. 79:137.
    2. Chargaff, E., 1950, "Chemical Specificity of Nucleic Acids and Mechanism of Their Degradation", Experientia G: 201-206.
    3. Conn, E.C., Stumpf, P.K., Bruening, G., Doi, R.H., 1987, "Outlines of Biochemistry", 5th ed., John Wiley & Sons, New York.
    4. Hershey, A.D., Chase, M., 1952, "Independent Function of Viral Protein and Nucleic Acid on Growth of Bacteriophage", J. Gen. Physiol. 36: 39-56.
    5. Kleinsmith, L.J., Kish, V.M., 1988, Principles of Cell Biology, Harper and Row Publishers, New York.
    6. Rees, A.R., Sternberg, M.J.E., 1984, "From Cells to Atoms", Blackwell Scientific Publications.
    7. Strickberger, M,W., 1985, "Genetics", 3rd ed., MacMillan Publishing Company, New York.
    8. Todoroska, E., 1991 , "Structural Diversity of DNA in Living Systems", Communciations from the School of Applied Sciences, Charles Sturt University-Mitchell.
    9. Watson, J.D., Hopkins, N.H., Roberts, J.W., Steitz, J.A., Weiner, A.M., 1987, "Molecular Biology of the Gene", 4th ed., The Benjamin/Cummings publishing Company Inc., Menlo Park, California.

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