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    in the 1950s, when watson and crick were working on their model of dna, which concepts were well accepted by the scientific community?


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    Discovery of DNA Double Helix: Watson and Crick

    The landmark ideas of Watson and Crick relied heavily on the work of other scientists. What did the duo actually discover?

    Many people believe that American biologist James Watson and English physicist Francis Crick discovered DNA in the 1950s. In reality, this is not the case. Rather, DNA was first identified in the late 1860s by Swiss chemist Friedrich Miescher. Then, in the decades following Miescher's discovery, other scientists--notably, Phoebus Levene and Erwin Chargaff--carried out a series of research efforts that revealed additional details about the DNA molecule, including its primary chemical components and the ways in which they joined with one another. Without the scientific foundation provided by these pioneers, Watson and Crick may never have reached their groundbreaking conclusion of 1953: that the DNA molecule exists in the form of a three-dimensional double helix.

    The First Piece of the Puzzle: Miescher Discovers DNA

    Although few people realize it, 1869 was a landmark year in genetic research, because it was the year in which Swiss physiological chemist Friedrich Miescher first identified what he called "nuclein" inside the nuclei of human white blood cells. (The term "nuclein" was later changed to "nucleic acid" and eventually to "deoxyribonucleic acid," or "DNA.") Miescher's plan was to isolate and characterize not the nuclein (which nobody at that time realized existed) but instead the protein components of leukocytes (white blood cells). Miescher thus made arrangements for a local surgical clinic to send him used, pus-coated patient bandages; once he received the bandages, he planned to wash them, filter out the leukocytes, and extract and identify the various proteins within the white blood cells. But when he came across a substance from the cell nuclei that had chemical properties unlike any protein, including a much higher phosphorous content and resistance to proteolysis (protein digestion), Miescher realized that he had discovered a new substance (Dahm, 2008). Sensing the importance of his findings, Miescher wrote, "It seems probable to me that a whole family of such slightly varying phosphorous-containing substances will appear, as a group of nucleins, equivalent to proteins" (Wolf, 2003).

    More than 50 years passed before the significance of Miescher's discovery of nucleic acids was widely appreciated by the scientific community. For instance, in a 1971 essay on the history of nucleic acid research, Erwin Chargaff noted that in a 1961 historical account of nineteenth-century science, Charles Darwin was mentioned 31 times, Thomas Huxley 14 times, but Miescher not even once. This omission is all the more remarkable given that, as Chargaff also noted, Miescher's discovery of nucleic acids was unique among the discoveries of the four major cellular components (i.e., proteins, lipids, polysaccharides, and nucleic acids) in that it could be "dated precisely... [to] one man, one place, one date."

    Laying the Groundwork: Levene Investigates the Structure of DNA

    Meanwhile, even as Miescher's name fell into obscurity by the twentieth century, other scientists continued to investigate the chemical nature of the molecule formerly known as nuclein. One of these other scientists was Russian biochemist Phoebus Levene. A physician turned chemist, Levene was a prolific researcher, publishing more than 700 papers on the chemistry of biological molecules over the course of his career. Levene is credited with many firsts. For instance, he was the first to discover the order of the three major components of a single nucleotide (phosphate-sugar-base); the first to discover the carbohydrate component of RNA (ribose); the first to discover the carbohydrate component of DNA (deoxyribose); and the first to correctly identify the way RNA and DNA molecules are put together.

    During the early years of Levene's career, neither Levene nor any other scientist of the time knew how the individual nucleotide components of DNA were arranged in space; discovery of the sugar-phosphate backbone of the DNA molecule was still years away. The large number of molecular groups made available for binding by each nucleotide component meant that there were numerous alternate ways that the components could combine. Several scientists put forth suggestions for how this might occur, but it was Levene's "polynucleotide" model that proved to be the correct one. Based upon years of work using hydrolysis to break down and analyze yeast nucleic acids, Levene proposed that nucleic acids were composed of a series of nucleotides, and that each nucleotide was in turn composed of just one of four nitrogen-containing bases, a sugar molecule, and a phosphate group. Levene made his initial proposal in 1919, discrediting other suggestions that had been put forth about the structure of nucleic acids. In Levene's own words, "New facts and new evidence may cause its alteration, but there is no doubt as to the polynucleotide structure of the yeast nucleic acid" (1919).

    Indeed, many new facts and much new evidence soon emerged and caused alterations to Levene's proposal. One key discovery during this period involved the way in which nucleotides are ordered. Levene proposed what he called a tetranucleotide structure, in which the nucleotides were always linked in the same order (i.e., G-C-T-A-G-C-T-A and so on). However, scientists eventually realized that Levene's proposed tetranucleotide structure was overly simplistic and that the order of nucleotides along a stretch of DNA (or RNA) is, in fact, highly variable. Despite this realization, Levene's proposed polynucleotide structure was accurate in many regards. For example, we now know that DNA is in fact composed of a series of nucleotides and that each nucleotide has three components: a phosphate group; either a ribose (in the case of RNA) or a deoxyribose (in the case of DNA) sugar; and a single nitrogen-containing base. We also know that there are two basic categories of nitrogenous bases: the purines (adenine [A] and guanine [G]), each with two fused rings, and the pyrimidines (cytosine [C], thymine [T], and uracil [U]), each with a single ring. Furthermore, it is now widely accepted that RNA contains only A, G, C, and U (no T), whereas DNA contains only A, G, C, and T (no U) (Figure 1).

    Source : www.nature.com

    Mastering Bio #4 (TEST 1) Flashcards

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    In the 1950s, when Watson and Crick were working on their model of DNA, which concepts were well accepted by the scientific community?

    Chromosomes are made up of protein and nucleic acid.

    Chromosomes are found in the nucleus.

    Genes are made of DNA.

    Genes are located on chromosomes.

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    Chromosomes are made up of protein and nucleic acid.

    Chromosomes are found in the nucleus.

    Genes are located on chromosomes.

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    What are the chemical components of a DNA molecule?

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    sugars nitrogenous bases phosphate groups

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    Terms in this set (11)

    In the 1950s, when Watson and Crick were working on their model of DNA, which concepts were well accepted by the scientific community?

    Chromosomes are made up of protein and nucleic acid.

    Chromosomes are found in the nucleus.

    Genes are made of DNA.

    Genes are located on chromosomes.

    Chromosomes are made up of protein and nucleic acid.

    Chromosomes are found in the nucleus.

    Genes are located on chromosomes.

    What are the chemical components of a DNA molecule?

    sugars nitrogenous bases phosphate groups

    In the early 1950s, many researchers were racing to describe the structure of DNA using different approaches. Which of the following statements is true?

    Jim Watson and Francis Crick built theoretical models, incorporating current knowledge about chemical bonding and X-ray data.

    Rosalind Franklin and Maurice Wilkins conducted genetic experiments to explore DNA's role in inheritance.

    Rosalind Franklin and Maurice Wilkins built theoretical models, incorporating current knowledge about chemical bonding and X-ray data.

    Jim Watson and Francis Crick used X-ray diffraction to understand the structure of DNA.

    Jim Watson and Francis Crick built theoretical models, incorporating current knowledge about chemical bonding and X-ray data.

    Early, flawed DNA models proposed by Watson and Crick and by Linus Pauling correctly described which property of DNA?

    Bases pair with complementary bases.

    DNA is composed of sugars, phosphates, and bases.

    Bases face the center of the molecule, with a phosphate backbone on the outside.

    DNA is a double helix.

    DNA is composed of sugars, phosphates, and bases.

    Erwin Chargaff observed that the proportions of adenine (A) and thymine (T) bases were always equal, as were the proportion of guanine (G) and cytosine (C). Chargaff's observation suggests which of the following statements?

    The data suggest that A would always pair with T and G would always pair with C in a DNA molecule.

    What are the components of a nucleotide?

    a sugar, a phosphate group and a nitrogenous base

    In a DNA double helix, what kind of chemical bonds form between the complementary nitrogenous bases?

    hydrogen bonds

    What is the structural feature that allows DNA to replicate?

    complementary pairing of the nitrogenous bases

    Which of the following did Watson and Crick already know when they were trying to determine the structure of DNA? The number of _____.

    purines is always the same as pyrimidines

    Which of the following best describes DNA's secondary structure?

    double antiparallel helical strands

    Nucleic acids have a definite polarity, or directionality. Stated another way, one end of the molecule is different from the other end. How are these ends described?

    One end has an unlinked 3 carbon; the other end has an unlinked 5 carbon.

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    The Discovery of the Double Helix, 1951

    The Discovery of the Double Helix, 1951-1953

    The discovery in 1953 of the double helix, the twisted-ladder structure of deoxyribonucleic acid (DNA), by James Watson and Francis Crick marked a milestone in the history of science and gave rise to modern molecular biology, which is largely concerned with understanding how genes control the chemical processes within cells. In short order, their discovery yielded ground-breaking insights into the genetic code and protein synthesis. During the 1970s and 1980s, it helped to produce new and powerful scientific techniques, specifically recombinant DNA research, genetic engineering, rapid gene sequencing, and monoclonal antibodies, techniques on which today's multi-billion dollar biotechnology industry is founded. Major current advances in science, namely genetic fingerprinting and modern forensics, the mapping of the human genome, and the promise, yet unfulfilled, of gene therapy, all have their origins in Watson and Crick's inspired work. The double helix has not only reshaped biology, it has become a cultural icon, represented in sculpture, visual art, jewelry, and toys.

    Researchers working on DNA in the early 1950s used the term "gene" to mean the smallest unit of genetic information, but they did not know what a gene actually looked like structurally and chemically, or how it was copied, with very few errors, generation after generation. In 1944, Oswald Avery had shown that DNA was the "transforming principle," the carrier of hereditary information, in pneumococcal bacteria. Nevertheless, many scientists continued to believe that DNA had a structure too uniform and simple to store genetic information for making complex living organisms. The genetic material, they reasoned, must consist of proteins, much more diverse and intricate molecules known to perform a multitude of biological functions in the cell.

    Crick and Watson recognized, at an early stage in their careers, that gaining a detailed knowledge of the three-dimensional configuration of the gene was the central problem in molecular biology. Without such knowledge, heredity and reproduction could not be understood. They seized on this problem during their very first encounter, in the summer of 1951, and pursued it with single-minded focus over the course of the next eighteen months. This meant taking on the arduous intellectual task of immersing themselves in all the fields of science involved: genetics, biochemistry, chemistry, physical chemistry, and X-ray crystallography. Drawing on the experimental results of others (they conducted no DNA experiments of their own), taking advantage of their complementary scientific backgrounds in physics and X-ray crystallography (Crick) and viral and bacterial genetics (Watson), and relying on their brilliant intuition, persistence, and luck, the two showed that DNA had a structure sufficiently complex and yet elegantly simple enough to be the master molecule of life.

    Other researchers had made important but seemingly unconnected findings about the composition of DNA; it fell to Watson and Crick to unify these disparate findings into a coherent theory of genetic transfer. The organic chemist Alexander Todd had determined that the backbone of the DNA molecule contained repeating phosphate and deoxyribose sugar groups. The biochemist Erwin Chargaff had found that while the amount of DNA and of its four types of bases--the purine bases adenine (A) and guanine (G), and the pyrimidine bases cytosine (C) and thymine(T)--varied widely from species to species, A and T always appeared in ratios of one-to-one, as did G and C. Maurice Wilkins and Rosalind Franklin had obtained high-resolution X-ray images of DNA fibers that suggested a helical, corkscrew-like shape. Linus Pauling, then the world's leading physical chemist, had recently discovered the single-stranded alpha helix, the structure found in many proteins, prompting biologists to think of helical forms. Moreover, he had pioneered the method of model building in chemistry by which Watson and Crick were to uncover the structure of DNA. Indeed, Crick and Watson feared that they would be upstaged by Pauling, who proposed his own model of DNA in February 1953, although his three-stranded helical structure quickly proved erroneous.

    The time, then, was ripe for their discovery. After several failed attempts at model building, including their own ill-fated three-stranded version and one in which the bases were paired like with like (adenine with adenine, etc.), they achieved their break-through. Jerry Donohue, a visiting physical chemist from the United States who shared Watson and Crick's office for the year, pointed out that the configuration for the rings of carbon, nitrogen, hydrogen, and oxygen (the elements of all four bases) in thymine and guanine given in most textbooks of chemistry was incorrect. On February 28, 1953, Watson, acting on Donohue's advice, put the two bases into their correct form in cardboard models by moving a hydrogen atom from a position where it bonded with oxygen to a neighboring position where it bonded with nitrogen. While shifting around the cardboard cut-outs of the accurate molecules on his office table, Watson realized in a stroke of inspiration that A, when joined with T, very nearly resembled a combination of C and G, and that each pair could hold together by forming hydrogen bonds. If A always paired with T, and likewise C with G, then not only were Chargaff's rules (that in DNA, the amount of A equals that of T, and C that of G) accounted for, but the pairs could be neatly fitted between the two helical sugar-phosphate backbones of DNA, the outside rails of the ladder. The bases connected to the two backbones at right angles while the backbones retained their regular shape as they wound around a common axis, all of which were structural features demanded by the X-ray evidence. Similarly, the complementary pairing of the bases was compatible with the fact, also established by the X-ray diffraction pattern, that the backbones ran in opposite direction to each other, one up, the other down.

    Source : profiles.nlm.nih.gov

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