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DNA the genetic material
The Chemical Nature of
A German chemist, Friedrich Miescher, discovered DNA in 1869, only four years after Mendel’s work was published.in 1869, only four years after Mendel’s work was published.Miescher extracted a white substance from the nuclei of human cells and fish sperm. The proportion of nitrogen
and phosphorus in the substance was different from that in any other known constituent of cells, which convinced Miescher
that he had discovered a new biological substance He called this substance “nuclein,” because it seemed to be specifically associated with the nucleus
DNA is a polymer
Because Miescher’s nuclein was slightly acidic, it came to be called nucleic acid. For 50 years biologists did little research on the substance, because nothing was known of its function in cells. In the 1920s, the basic structure of nucleic acids was determined by the biochemist P. A. Levene, who found that DNA contains three main components: (1) phosphate (PO4) groups;(2) five-carbon sugars; and (3) nitrogen-containing bases called purines (adenine, A, and guanine, G) and pyrimidines (thymine, T, and cytosine, C; RNA contains uracil, U, instead of T). From the roughly equal proportions of these components, Levene concluded correctly that DNA and RNA molecules are made of repeating units of the three components. Each unit, consisting of a sugar attached to a phosphate group and a base, is called
a nucleotide. The identity of the base distinguishes one nucleotide from another.To identify the various chemical groups in DNA and RNA, it is customary to number the carbon atoms of the base and the sugar and then refer to any chemical group attached to a carbon atom by that number.
In the sugar,four of the carbon atoms together with an oxygen atom form a five-membered ring.
The carbon atoms are numbered 1′ to 5′, proceeding clockwise from the oxygen atom; the prime symbol (′) indicates that the number refers to a carbon in a sugar rather than a base.Under this numbering scheme, the phosphate group is attached to the 5′ carbon atom of the sugar, and the base is attached to the 1′ carbon atom.Inaddition, a free hydroxyl (—OH) group is attached to the 3′ carbon atom.The 5′ phosphate and 3′ hydroxyl groups allow DNA and RNA to form long chains of nucleotides, because these two groups can react chemically with each other.The reaction between the phosphate group of one nucleotide and the hydroxyl group of another is a dehydration synthesis, eliminating a water molecule and forming a covalent bond that links the two groups
The linkage is called a phosphodiester bond because the phosphate group is now linked to the
two sugars by means of a pair of ester (P—O—C) bonds. The two-unit polymer resulting from this reaction still has a free 5′ phosphate group at one end and a free 3′ hydroxyl group at the other, so it can link to other nucleotides. In this way, many thousands of nucleotides can join together in long chains.Linear strands of DNA or RNA, no matter how long, will almost always have a free 5′ phosphate group at one end and a free 3′ hydroxyl group at the other. Therefore,every DNA and RNA molecule has an intrinsic directionality, and we can refer unambiguously to each end of the molecule.By convention, the sequence of bases is usually expressed in the 5′-to-3′ direction.Thus, the base sequence “GTCCAT” refers to the sequence,5′ pGpTpCpCpApT—OH 3′ where the phosphates are indicated by “p.” Note that this is not the same molecule as that represented by the reverse sequence: 5′ pTpApCpCpTpG—OH 3′ Levene’s early studies indicated that all four types of DNA nucleotides were present in roughly equal amounts. This result,which later proved to be erroneous, led to the mistaken idea that DNA was a simple polymer in which the four nucleotides merely repeated (for instance,GCAT . . . GCAT . . . GCAT . . . GCAT . . .). If the sequence never varied, it was difficult to see how DNA might contain the hereditary information; this was why Avery’s conclusion that DNA is the transforming principle was not readily accepted at first. It seemed more plausible that DNA was simply a structural element of the chromosomes, with proteins playing the central genetic role.
Watson and Crick: A Model of the Double Helix
In 1953, James Watson and Francis Crick, two young investigators at Cambridge University, quickly worked out a likely structure for the DNA molecule They analyzed the problem deductively, first building models of the nucleotides, and then trying to assemble the nucleotides into a molecule that matched what was known about the structure of DNA. They tried various possibilities before they finally hit on the idea that the molecule might be a simple double helix, with the bases of two strands pointed inward toward each other, forming base-pairs. In their model, basepairs always consist of purines, which are large, pointing toward pyrimidines,which are small, keeping the diameter of the molecule a constant 2 nanometers. Because hydrogen bonds can form between the bases in a base-pair, the double helix is stabilized as a duplex DNA molecule composed of two antiparallel strands, one chain running 3′ to 5′ and the other 5′ to 3′. The base-pairs are planar (flat) and stack 0.34 nm apart as a result of hydrophobic interactions,contributing to the overall stability of the molecule.The Watson–Crick model explained why Chargaff had obtained the results he had: in a double helix,adenine forms two hydrogen bonds with thymine, but it will not form hydrogen bonds properly with cytosine.Similarly, guanine forms three hydrogen bonds with cytosine, but it will not form hydrogen bonds properly with thymine. Consequently, adenine and thymine will always occur in the same proportions in any DNA molecule,as will guanine and cytosine.