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Morgans group showed that genes are located on chromosomes, the two chemical components of chromosomesDNA and proteinbecame the candidates for the genetic material. Frederick Griffith, a British medical officer then discovered of the genetic role of DNA back to 1928. Additional Evidence That DNA Is the Genetic Material Further evidence that DNA is the genetic material came from the laboratory of biochemist Erwin Chargaff. It was already known that DNA is a polymer of nucleotides, each consisting of three components: a nitrogenous (nitrogencontaining) base, a pentose sugar called deoxyribose, and a phosphate group (Figure 16.5). The base can be adenine (A), thymine (T), guanine (G), or cytosine (C). Chargaff analyzed the base composition of DNA from a number of different organisms. In 1947, he reported that DNA composition varies from one species to another. For example, 30.3% of human DNA nucleotides have the base A, whereas DNA from the bacterium E. coli has only 26.0% A. This evidence of molecular diversity among species, which had been presumed absent from DNA, made DNA a more credible candidate for the genetic material. Chargaff also found a peculiar regularity in the ratios of nucleotide bases within a single species. In the DNA of each species he studied, the number of adenines approximately equaled the number of thymines, and the number of guanines approximately equaled the number of cytosines. In human DNA, for example, the four bases are present in these percentages: A = 30.3% and T = 30.3%; G = 19.5% and C = 19.9%. The equivalences for any given species between the number of A and T bases and the number of G and C bases became known as Chargaffs rules. The basis for these rules remained unexplained until the discovery of the double helix. Additional circumstantial evidence was consistent with DNA being the genetic material in eukaryotes. Prior to mitosis, a eukaryotic cell exactly doubles its DNA content, and during mitosis, this DNA is distributed equally to the two daughter cells. Also, in a given species, a diploid set of chromosomes has twice as much DNA as the haploid set. Building a Structural Model of DNA: Scientific Inquiry Once most biologists were convinced that DNA was the genetic material, the challenge was to determine how the structure of DNA could account for its role in inheritance. By the early 1950s, the arrangement of covalent bonds in a nucleic acid polymer was well established (see Figure 16.5), and researchers focused on discovering the threedimensional structure of DNA. Among the scientists working on the problem were Linus Pauling, in California, and Maurice Wilkins and Rosalind Franklin, in London. First to come up with the correct answer, however, were two scientists who were relatively unknown at the timethe American James Watson and the Englishman Francis Crick. The brief but celebrated partnership that solved the puzzle of DNA began soon after Watson journeyed to Cambridge University, where Crick was studying protein structure with a technique called Xray crystallography (see Figure 5.24). While visiting the laboratory of Maurice Wilkins at Kings College in London, Watson saw an Xray diffraction image of DNA produced by Wilkinscolleague Rosalind Franklin (Figure 16.6a). Images produced by Xray crystallography are not actually pictures of molecules. The spots and smudges in Figure 16.6b were produced by Xrays that were diffracted (deflected) as they passed through aligned fibers of purified DNA. Crystallographers use mathematical equations to translate such patterns into information about the threedimensional shapes of molecules, and Watson was familiar with the types of patterns that helical molecules produce. Just a glance at Franklins Xray diffraction photo of DNA not only told him that DNA was helical in shape, but also enabled him to deduce the width of the helix and the spacing of

the nitrogenous bases along it. The width of the helix suggested that it was made up of two strands, contrary to a threestranded model that Linus Pauling had recently proposed. The presence of two strands accounts for the nowfamiliar term double helix (Figure 16.7).Watson and Crick began building models of a double helix that would conform to the Xray measurements and what was then known about the chemistry of DNA. Having read an annual report summarizing Franklins work, they knew she had concluded that the sugarphosphate backbones were on the outside of the double helix. This arrangement was appealing because it put the relatively hydrophobic nitrogenous bases in the molecules interior and thus away from the surrounding aqueous solution. Watson constructed a model with the nitrogenous bases facing the interior of the double helix (see Figure 16.7). You can imagine this arrangement as a rope ladder with rigid rungs. The side ropes are the equivalent of the sugar phosphate backbones, and the rungs represent pairs of nitrogenous bases. Now imagine the ladder twisted into a spiral. Franklins Xray data indicated that the helix makes one full turn every 3.4 nm along its length. With the bases stacked just 0.34 nm apart, there are ten layers of base pairs, or rungs of the ladder, in each turn of the helix. The nitrogenous bases of the double helix are paired in specific combinations: adenine (A) with thymine (T), and guanine (G) with cytosine (C). It was mainly by trial and error that Watson and Crick arrived at this key feature of DNA. At first, Watson imagined that the bases paired like with likefor example, A with A and C with C. But this model did not fit the Xray data, which suggested that the double helix had a uniform diameter. Why is this requirement inconsistent with like withlike pairing of bases? Adenine and guanine are purines, nitrogenous bases with two organic rings. In contrast, cytosine and thymine belong to the family of nitrogenous bases known as pyrimidines, which have a single ring. Thus, purines (A and G) are about twice as wide as pyrimidines (C and T). A purinepurine pair is too wide and a pyrimidinepyrimidine pair too narrow to account for the 2nm diameter of the double helix. Always pairing a purine with a pyrimidine, however, results in a uniform diameter.Watson and Crick reasoned that there must be additional specificity of pairing dictated by the structure of the bases. Each base has chemical side groups that can form hydrogen bonds with its appropriate partner: Adenine can form two hydrogen bonds with thymine and only thymine; guanine forms three hydrogen bonds with cytosine and only cytosine. In shorthand, A pairs with T, and G pairs with C (Figure 16.8).The WatsonCrick model explained the basis for Chargaffs rules. Wherever one strand of a DNA molecule has an A, the partner strand has a T. And a G in one strand is always paired with a C in the complementary strand. Therefore, in the DNA of any organism, the amount of adenine equals the amount of thymine, and the amount of guanine equals the amount of cytosine. Although the basepairing rules dictate the combinations of nitrogenous bases that form the rungs of the double helix, they do not restrict the sequence of nucleotides along each DNA strand. The linear sequence of the four bases can be varied in countless ways, and each gene has a unique order, or base sequence. In April 1953, Watson and Crick surprised the scientific world with a succinct, onepage paper in the British journal Nature. J. D. Watson and F. H. C. Crick, Molecular Structure of Nucleic Acids: A Structure for Deoxynucleic Acids. Nature 171 (1953): 738. * The paper reported their molecular model for DNA: the double helix, which has since become the symbol of molecular biology. The beauty of the model was that the structure of DNA suggested the basic mechanism of its replication
Sources: Nobel Prize: What's a Genome: Science Photo Library: Nature: Biography of James Watson: Biography of Francis Crick:

The Race to Solve the Mystery: The Structure of DNA

Working together at the University of Cambridge in England, James Watson, an American scientist, and Francis Crick, a British researcher, made a major scientific breakthrough when they discovered the famous "double helix" -the structure of DNA, the molecule of life. In the April 25, 1953, issue of the science journal Nature,Watson and Crick wrote: ""We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest." Those modest words were an understatement. Nine years later, in 1962, they received the Nobel Prize for answering one of science's long-pondered mysteries, advancing the emerging field of molecular biology in the process. Watson and Crick's quest helps illustrate how collaboration, creativity, hard work, and serendipity often conspire on the path to scientific achievement. A Eureka Moment Deoxyribonucleic acid (DNA) was first isolated in 1869 by the Swiss scientist Friedrich Miescher. He called the white, slightly acidic chemical that he found in cells "nuclein." By the late 1940s, scientists knew what DNA contained -phosphate, sugar, and four nitrogen-containing chemical "bases": adenine (A), thymine (T), guanine (G), and cytosine (C). But no one had figured out what the DNA molecule looked like. In 1953, Linus Pauling, the great American chemist, claimed to have discovered the structure of the DNA molecule, but when Watson saw Pauling's research paper (which had not yet been published) on January 28, 1953, he knew it was wrong. A few days later at King's College in London, Watson was shown an X-ray diffraction photograph (see left) of the DNA crystal taken by scientist Rosalind Franklin. "The instant I saw the picture, my mouth fell open and my pulse began to race," wrote Watson in his book The Double Helix (1968). The photo convinced him that the DNA molecule must consist of two chains arranged in a paired helix, which resembles a spiral staircase or ladder.

Watson and Crick set about developing a stick-and-ball model of DNA's possible structure. The sides of the ladder were made up of alternating molecules of phosphate and the sugar deoxyribose, while each rung on the ladder was composed of a pair of nitrogencontaining bases connected in the middle. At first, the scientists were uncertain how DNA's four bases -- A, T, C, and G -- link up with each other. Then thanks to a suggestion from a colleague, they realized that the bases always join up with the same partners - A with T, and C with G. On March 7, 1953, Watson and Crick finished their model, which reached 6 feet tall. "A Structure for Deoxyribose Nucleic Acid" was published in Nature on April 25, 1953. By the late 1950s, their work had been widely accepted by the scientific community. In 1962, Watson and Crick received the Nobel Prize for Physiology or Medicine with Maurice Wilkins. He had published important crystallography work relating to DNA at the same time as Watson and Crick. Rosalind Franklin, whose photograph provided "a Eureka moment" for Watson, died in 1958 of cancer. Scientists wonder if she would have been honored with the award as well, had she lived.

The DNA molecule resembles a spiral staircase or ladder. The sides of the ladder are made up of alternating molecules of phosphate and the sugar deoxyribose, while each rung is composed of a pair of nitrogencontaining chemical bases connected in the middle. DNA has four bases Adenine, Thymine, Cytosine, and Guanine. These bases always join up with the same partners - A with T, and C with G. Graphic courtesy of Craig Venter Institute.

J.D.Watson and F.H.C. Crick, Molecular Structure of Nucleic Acids: A Structure for Deoxynucleic Acids. Nature 171 [1953]:738 Watson & Crick - Model of DNA helix. Image courtesy of

Bibliography 1) Merit Students Encyclopedia (C) 1980. By: Macillia Educational Corporation 2) 1996 By J. Stein Carter 3) Encyclopedia Americana. US Constitution Bicentennial Commemorative Edition. By: Grolier Incorporatied (C) 1987

Genes & Genomes: A Changing Perspective

By Maxine Singer, Paul Berg publication 1991 vol-19 issue-4 Pg:-36-42