DNA: The Making

Lyle Sykes



For more than 50 years after the science of genetics was established and the patterns of inheritance through genes were clarified, the largest questions remained unanswered: How are the chromosomes and their genes copied so exactly from cell to cell, and how do they direct the structure and behavior of living things? This paper will discuss those questions and the people that answered them.
Two American geneticists, George Wells Beadle and Edward Lawrie Tatum, provided one of the first important clues in the early 1940s. Working with the fungi Neurospora and Penicillium, they found that “genes direct the formation of enzymes through the units of which they are composed.” (Annas 1996) Each unit (a polypeptide) is produced by a specific gene. This work launched studies into the chemical nature of the gene and helped to establish the field of molecular genetics.
“The fact that chromosomes were almost entirely composed of two kinds of chemical substances, protein and nucleic acids, had long been known. Partly because of the close relationship established between genes and enzymes, which are proteins, protein at first seemed the fundamental substance that determined heredity.” (Goetinck 1995) “In 1944, however, the Canadian bacteriologist Oswald Theodore Avery proved that deoxyribonucleic acid (DNA) performed this role. He extracted DNA from one strain of bacteria and introduced it into another strain. The second strain not only acquired characteristics of the first but passed them on to subsequent generations. By this time DNA was known to be made up of substances called nucleotides. Each nucleotide consists of a phosphate, a sugar known as deoxyribose, and any one of four nitrogen-containing bases. The four nitrogen bases are adenine (A), thymine (T), guanine (G), and cytosine (C).”(Caldwell 1996)
“In 1953, putting together the accumulated chemical knowledge, geneticists James Dewey Watson of the U.S. and Francis Harry Compton Crick of Great Britain worked out the structure of DNA. This knowledge immediately provided the means of understanding how hereditary information is copied. Watson and Crick found that the DNA molecule is composed of two long strands in the form of a double helix, somewhat resembling a long, spiral ladder. The strands, or sides of the ladder, are made up of alternating phosphate and sugar molecules. The nitrogen bases, joining in pairs, act as the rungs. Each base is attached to a sugar molecule and is linked by a hydrogen bond to a complementary base on the opposite strand.” (Caldwell 1996) “Adenine always binds to thymine, and guanine always binds to cytosine.” (Annas 1996) “To make a new, identical copy of the DNA molecule, the two strands need only unwind and separate at the bases (which are weakly bound); with more nucleotides available in the cell, new complementary bases ca
n link with each separated strand, and two double helixes result. Since the “backbone” of every chromosome is a single long, double-stranded molecule of DNA, the production of two identical double helixes will result in the production of two identical chromosomes.” (Caldwell 1996)
“The DNA backbone is actually a great deal longer than the chromosome but is tightly coiled up within it. This packing is now known to be based on minute particles of protein known as nucleosomes, just visible under the most powerful electron microscope. The DNA is wound around each nucleosome in succession to form a beaded structure. The structure is then further folded so that the beads associate in regular coils. Thus, the DNA has a “coiled-coil” configuration, like the filament of an electric light bulb.” (Popper 1996)
“After the discoveries of Watson and Crick, the question that remained was how the DNA directs the formation of proteins, compounds central to all the processes of life. Proteins are not only the major components of most cell structures, they also control virtually all the chemical reactions that occur in living matter. The ability of a protein to act as part of a structure, or as an enzyme affecting the rate of a particular chemical reaction, depends on its molecular shape. This shape, in turn, depends on its composition. Every protein is made up of one or more components called polypeptides, and each polypeptide is a chain of subunits called amino acids. Twenty different amino acids are commonly found in polypeptides.” (Caldwell 1996) “The number, type, and order of amino acids in a chain ultimately determine the structure and function of the protein of which the chain is a part.” (Marx 1996)
“Since proteins were shown to be products of genes, and each gene was shown to be composed of sections of DNA strands, scientists reasoned that a genetic code must exist by which the order of the four nucleotide bases in the DNA could direct the sequence of amino acids in the formation of polypeptides.” (Barinaga 1995) “In other words, a process must exist by which the nucleotide bases transmit information that dictates protein synthesis. This process would explain how the genes control the forms and functions of cells, tissues, and organisms. Because only four different kinds of nucleotides occur in DNA, but 20 different kinds of amino acids occur in proteins, the genetic code could not be based on one nucleotide specifying one amino acid. Combinations of two nucleotides could only specify 16 amino acids (4� = 16), so the code must be made up of combinations of three or more successive nucleotides. The order of the triplets—or, as they came to be called, codons—could define the order of the amino acids in the
polypeptide.” (Snaz 1996)
“Ten years after Watson and Crick reported the DNA structure, the genetic code was worked out and proved biologically. Its solution depended on a great deal of research involving another group of nucleic acids, the ribonucleic acids (RNA). The specification of a polypeptide by the DNA was found to take place indirectly, through an intermediate molecule known as messenger RNA (mRNA). Part of the DNA somehow uncoils from its chromosome packing, and the two strands become separated for a portion of their length. One of them serves as a template upon which the mRNA is formed (with the aid of an enzyme called RNA polymerase). The process is very similar to the formation of a complementary strand of DNA during the division of the double helix, except that RNA contains uracil (U) instead of thymine as one of its four nucleotide bases, and the uracil (which is similar to thymine) joins with the adenine in the formation of complementary pairs. Thus, a sequence adenine-guanine-adenine-thymine-cytosine (AGATC) in the cod
ing strand of the DNA produces a sequence uracil-cytosine-uracil-adenine-guanine (UCUAG) in the mRNA.” (Witten 1996)
“The production of a strand of messenger RNA by a particular sequence of DNA is called transcription. While the transcription is still taking place, the mRNA begins to detach from the DNA. Eventually one end of the new mRNA molecule, which is now a long, thin strand, becomes inserted into a small structure called a ribosome, in a manner much like the insertion of a thread into a bead. As the ribosome bead moves along the mRNA thread, the end of the thread may be inserted into a second ribosome, and so on.” (Lemonick 1996) Using a very high-powered microscope and special staining techniques, scientists can photograph mRNA molecules with their associated ribosome beads.
“Ribosomes are made up of protein and RNA. A group of ribosomes linked by mRNA is called a polyribosome or polysome. As each ribosome passes along the mRNA molecule, it “reads” the code, that is, the sequence of nucleotide bases on the mRNA. The reading, called translation, takes place by means of a third type of RNA molecule called transfer RNA (tRNA), which is produced on another segment of the DNA. On one side of the tRNA molecule is a triplet of nucleotides. On the other side is a region to which one specific amino acid can become attached (with the aid of a specific enzyme). The triplet on each tRNA is complementary to one particular sequence of three nucleotides—the codon—on the mRNA strand. Because of this complementary, the triplet is able to “recognize” and adhere to the codon. For example, the sequence uracil-cytosine-uracil (UCU) on the strand of mRNA attracts the triplet adenine-guanine-adenine (AGA) of the tRNA. The tRNA triplet is known as the anticodon.” (Witten 1995)
“As tRNA molecules move up to the strand of mRNA in the ribosome beads, each bears an amino acid. The sequence of codons on the mRNA therefore determines the order in which the amino acids are brought by the tRNA to the ribosome. In association with the ribosome, the amino acids are then chemically bonded together into a chain, forming a polypeptide. The new chain of polypeptide is released from the ribosome and folds up into a characteristic shape that is determined by the sequence of amino acids. The shape of a polypeptide and its electrical properties, which are also determined by the amino acid sequence, dictate whether it remains single or becomes joined to other polypeptides, as well as what chemical function it subsequently fulfills within the organism.” (Witten 1996)
“In bacteria, viruses, and blue-green algae, the chromosome lies free in the cytoplasm, and the process of translation may start even before the process of transcription (mRNA formation) is completed. In higher organisms, however, the chromosomes are isolated in the nucleus and the ribosomes are contained only in the cytoplasm. Thus, translation of mRNA into protein can occur only after the mRNA has become detached from the DNA and has moved out of the nucleus.” (O’Brien 1996)
As funding for research becomes available for scientist, they continue to study the DNA molecule with hopes of find the secrets that are hidden with in our own bodies. Their findings continue to aid us in cures and the prevention of many illnesses that years ago we couldn’t solve. Hopefully the research will soon pay off, with the cure for cancer or Alzheimer’s Disease, for instance. Only time will tell what discoveries will be made to help those that are ill. The sad thing is, most that are ill have very little time to spare. That is why the DNA research is important now, to save the ones that aren’t in need.

Bibliography


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