What are the structure and function of DNA?
Deoxyribonucleic acid (DNA) is the genetic material found in all cells. Chemically, it is classified as a nucleic acid, a relatively simple molecule composed of nucleotides. A nucleotide consists of a sugar (deoxyribose), a phosphate group, and one of the nitrogenous bases: adenine (A), cytosine (C), guanine (G), or thymine (T). In fact, nucleotides differ only in the particular nitrogenous base that they contain. Ribonucleic acid (RNA) is the other type of nucleic acid found in the cell; however, it contains ribose as its sugar instead of deoxyribose and has the nitrogenous base uracil (U) instead of thymine. Nucleotides can be assembled into long chains of nucleic acid via connections between the sugar on one nucleotide and the phosphate group on the next, thereby creating a sugar-phosphate “backbone” in the molecule. The nitrogenous base on each nucleotide is positioned such that it is perpendicular to the backbone, as shown in the following diagram:
Any one of the four DNA nucleotides (A, C, G, or T) can be used at any position in the molecule; it is therefore the specific sequence of nucleotides in a DNA molecule that makes it unique and able to carry genetic information. The genetic information is the sequence itself.
In the cell, DNA exists as a double-stranded molecule; this means that it consists of two chains of nucleotides side by side. The double-stranded form of DNA can most easily be visualized as a ladder, with the sugar-phosphate backbones being the sides of the ladder and the nitrogenous bases being the rungs of the ladder, as shown in the following diagram:
This ladder is then twisted into a spiral shape. Any spiral-shaped molecule is called a “helix,” and since each strand of DNA is wound into a spiral, the complete DNA molecule is often called a “double helix.” This molecule is extremely flexible and can be compacted to a great degree, thus allowing the cell to contain large amounts of genetic material.
Nucleic acids were discovered in 1869 by the physician Friedrich Miescher. He isolated these molecules, which he called nuclein, from the nuclei of white blood cells. This was the first association of nucleic acids with the nucleus of the cell. In the 1920s, experiments performed by other scientists showed that DNA could be located on the chromosomes within the nucleus. This was strong evidence for the role of DNA in heredity, since at that time there was already a link between the activities of chromosomes during cell division and the inheritance of particular traits, largely because of the work of the geneticist Thomas Hunt Morgan about ten years earlier.
However, it was not immediately apparent, based on this evidence alone, that DNA was the genetic material. In addition to DNA, proteins are present in the nucleus of the cell and are an integral part of chromosomes as well. Proteins are also much more complex molecules than nucleic acids, having a greater number of building blocks; there are twenty amino acids that can be used to build proteins, as opposed to only four nucleotides for DNA. Moreover, proteins tend to be much more complex than DNA in terms of their three-dimensional structure as well. Therefore, it was not at all clear in the minds of many scientists of the time that DNA had to be the genetic material, since proteins could not specifically be ruled out.
In 1928, the microbiologist Frederick Griffith supplied some of the first evidence that eventually led to the identification of DNA as the genetic material. Griffith’s research involved the bacterium Streptococcus pneumoniae, a common cause of lung infections. He was working primarily with two different strains of this bacterium: a strain that was highly virulent (able to cause disease) and a strain that was nonvirulent (not able to cause disease). Griffith noticed that if he heat-killed the virulent strain and then mixed its cellular debris with the living, nonvirulent strain, the nonvirulent strain would be “transformed” into a virulent strain. He did not know what part of the heat-killed virulent cells was responsible for the transformation, so he simply called it the “transforming factor” to denote its activity in his experiment. Unfortunately, Griffith never took the next step necessary to reveal the molecular identity of this transforming factor.
That critical step was taken by another microbiologist, Oswald Avery, and his colleagues in 1944. Avery essentially repeated Griffith’s experiments with two important differences: Avery partially purified the heat-killed virulent strain preparation and selectively treated this preparation with a variety of enzymes to see if the transforming factor could be eliminated, thereby eliminating the transformation itself. Avery showed that transformation was prevented only when the preparation was treated with deoxyribonuclease, an enzyme that specifically attacks and destroys DNA. Other enzymes that specifically destroy RNA or proteins could not prevent transformation from occurring. This was extremely strong evidence that the genetic material was DNA.
Experiments performed in 1952 by molecular biologists Alfred Hershey and Martha Chase using the bacterial virus T2 finally demonstrated conclusively that DNA was indeed the genetic material. Hershey and Chase studied how T2 infects bacterial cells to determine what part of the virus, DNA or protein, was responsible for causing the infection, thinking that whatever molecule directed the infection would have to be the genetic material of the virus. They found that DNA did directly participate in infection of the cells by entering them, while the protein molecules of the viruses stayed outside the cells. Most strikingly, they found that the original DNA of the “parent” virusesshowed up in the “offspring” viruses produced by the infection, directly demonstrating inheritance of DNA from one generation to another. This was an important element of the argument for DNA as the genetic material.
With DNA conclusively identified as the genetic material, the next step was to determine the structure of the molecule. This was finally accomplished when the double-helix model of DNA was proposed by molecular biologists James Watson and Francis Crick in 1953. This model has a number of well-defined and experimentally determined characteristics. For example, the diameter of the molecule, from one sugar-phosphate backbone to the other, is 20 angstroms. (There are 10 million angstroms in one millimeter, which is one-thousandth of a meter.) There are 3.4 angstroms from one nucleotide to the next, and the entire double helix makes one turn for every ten nucleotides, a distance of about 34 angstroms. These measurements were determined by the physicists Maurice Wilkins and Rosalind Franklin around 1951 using a process called x-ray diffraction, in which crystals of DNA are bombarded with x-rays; the resulting patterns captured on film gave Wilkins and Franklin, and later Watson and Crick, important clues about the physical structure of DNA.
Another important aspect of Watson and Crick’s double-helix model is the interaction between the nitrogenous bases in the interior of the molecule. Important information about the nature of this interaction was provided by molecular biologist Erwin Chargaff in 1950. Chargaff studied the amounts of each nitrogenous base present in double-stranded DNA from organisms as diverse as bacteria and humans. He found that no matter what the source of the DNA, the amount of adenine it contains is always roughly equal to the amount of thymine; there are also equal amounts of guanine and cytosine in DNA. This information led Watson and Crick to propose an interaction, or base pairing, between these sets of bases such that A always base pairs with T (and vice versa) and G always base pairs with C. Another name for this phenomenon is complementary base pairing: A is said to be the complement of T, and so on.
The force that holds complementary bases, and therefore the two strands of DNA, together is a weak chemical interaction called a hydrogen bond, which is created whenever a hydrogen atom in one molecule has an affinity for nitrogen or oxygen atoms in another molecule. The affinity of the atoms for each other draws the molecules together in the hydrogen bond. A-T pairs have two hydrogen bonds between them because of the chemical structure of the bases, whereas G-C pairs are connected by three hydrogen bonds, making them slightly stronger and more stable than A-T pairs. The entire DNA double helix, although it is founded upon the hydrogen bond, one of the weakest bonds in nature, is nonetheless an extraordinarily stable structure because of the combined force of the millions of hydrogen bonds holding most DNA molecules together. However, these hydrogen bonds can be broken under certain conditions in the cell. This usually occurs as part of the process of the replication of the double helix, in which the two strands of DNA must come apart in order to be duplicated. In the cell, the hydrogen bonds are broken with the help of enzymes. Under artificial conditions in the laboratory, hydrogen bonds in the double helix can easily be broken just by heating a solution of DNA to high temperatures (close to the boiling point).
Watson and Crick were careful to point out that their double-helix model of DNA was the first model to immediately suggest a mechanism by which the molecule could be replicated. They knew that this replication, which must occur before the cell can divide, would be a necessary characteristic of the genetic material of the cell and that an adequate model of DNA must help explain how this duplication could occur. Watson and Crick realized that the mechanism of complementary base pairing that was an integral part of their model was a potential answer to this problem. If the double helix is separated into its component single-strand molecules, each strand will be able to direct the replacement of the opposite, or complementary, strand by base pairing properly with only the correct nucleotides. For example, if a single-strand DNA molecule has the sequence TTAGTCA, the opposite complementary strand will always be AATCAGT; it is as if the correct double-stranded structure is “built in” to each single strand. Additionally, as each of the single strands in a double-strand DNA molecule goes through this addition of complementary nucleotides, two new DNA double helices are produced where there was only one before. Further, these new DNA molecules are completely identical to each other, barring any mistakes that might have been made in the replication process.
A strand of DNA also has a certain direction built into it; the DNA double helix is often called antiparallel in reference to this aspect of its structure. Antiparallel means that although the two strands of the DNA molecule are essentially side by side, they are oriented in different directions relative to the position of the deoxyribose molecules on the backbone of the molecule. To help keep track of the orientation of the DNA molecule, scientists often refer to a 5′ to 3′ direction. This designation comes from numbering the carbon atoms on the deoxyribose molecule (from 1′ to 5′) and takes note of the fact that the deoxyribose molecules on the DNA strand are all oriented in the same direction in a head-to-tail fashion. If it were possible to stand on a DNA molecule and walk down one of the sugar-phosphate backbones, one would encounter a 5′ carbon atom on a sugar, then the 3′ carbon, and so on all the way down the backbone. If one were walking on the other strand, the 3′ carbon atom would always be encountered before the 5′ carbon. The concept of an antiparallel double helix has important implications for the ways that DNA is produced and used in the cell. Generally, the cellular enzymes that are involved in processes concerning DNA are restricted to recognizing just one direction. For example, DNA polymerase, the enzyme that is responsible for making DNA in the cell, can only make DNA in a 5′ to 3′ direction, never the reverse.
Watson and Crick postulated a right-handed helix as part of their double-helix model; this means that the strands of DNA turn to the right, or in a counterclockwise fashion. This is now regarded as the “biological” (B) form of DNA because it is the form present inside the nucleus of the cell and in solutions of DNA. However, it is not the only possible form of DNA. In 1979, an additional form of DNA was discovered by molecular biologist Alexander Rich that exhibited a zigzag, left-handed double helix; he called this form of DNA Z-DNA. Stretches of alternating G and C nucleotides most commonly give rise to this conformation of DNA, and scientists think that this alternative form of the double helix is important for certain processes in the cell in which various molecules bind to the double helix and affect its function.
DNA plays two major roles in the cell. The first is to serve as a storehouse of the cell’s genetic information. Normally, cells have only one complete copy of their DNA molecules, and this copy is, accordingly, highly protected. DNA is a chemically stable molecule; it resists damage or destruction under normal conditions, and, if it is damaged, the cell has a variety of mechanisms to ensure the molecule is rapidly repaired. Furthermore, when the DNA in the cell is duplicated in a process called DNA replication, this duplication occurs in a regulated and precise fashion so that a perfect copy of DNA is produced. Once the genetic material of the cell has been completely duplicated, the cell is ready to divide in two in a process called mitosis. After cell division, each new cell of the pair will have a perfect copy of the genetic material; thus these cells will be genetically identical to each other. DNA thus provides a mechanism by which genetic information can be transferred easily from one generation of cells (or organisms) to another.
The second role of DNA is to serve as a blueprint for the ultimate production of proteins in the cell. This process occurs in two steps. The first step is the conversion of the genetic information in a small portion of the DNA molecule, called a gene, into messenger RNA (mRNA). This process is called transcription, and here the primary role of the DNA molecule is to serve as a template for synthesis of the mRNA molecule. The second step, translation, does not involve DNA directly; rather, the mRNA produced during transcription is in turn used as genetic information to produce a molecule of protein. However, it is important to note that genetic information originally present in the DNA molecule indirectly guides the synthesis and final amino acid sequence of the finished protein. Both of these steps, transcription and translation, are often called gene expression. A single DNA molecule in the form of a chromosome may contain thousands of different genes, each providing the information necessary to produce a particular protein. Each one of these proteins will then fulfill a particular function inside or outside the cell.
Knowledge of the physical and chemical structure of DNA and its function in the cell has undoubtedly had far-reaching effects on the science of biology. However, one of the biggest effects has been the creation of a new scientific discipline: molecular biology. With the advent of Watson and Crick’s double-helix model of DNA, it became clear to many scientists that, perhaps for the first time, many of the important molecules in the cell could be studied in detail and that the structure and function of these molecules could also be elucidated. Within fifteen years of Watson and Crick’s discovery, a number of basic genetic processes in the cell had been either partially or completely detailed, including DNA replication, transcription, and translation. Certainly the seeds of this revolution in biology were being planted in the decades before Watson and Crick’s 1953 model, but it was the double helix that allowed scientists to investigate the important issues of genetics on the cellular and molecular levels.
An increased understanding of the role DNA plays in the cell has also provided scientists with tools and techniques for changing some of the genetic characteristics of cells. This is demonstrated by the rapidly expanding field of genetic engineering, in which scientists can precisely manipulate DNA and cells on the molecular level to achieve a desired result. Additionally, more complete knowledge of how the cell uses DNA has opened windows of understanding into abnormal cellular processes such as cancer, which is fundamentally a defect involving the cell’s genetic information or the expression of that information.
Through the tools of molecular genetics, many scientists hope to be able to correct almost any genetic defect that a cell or an organism might have, including cancer or inherited genetic defects. The area of molecular biology that is concerned with using DNA as a way to correct cellular defects is called gene therapy. This is commonly done by inserting a normal copy of a gene into cells that have a defective copy of the same gene in the hope that the normal copy will take over and eliminate the effects of the defective gene. It is hoped that this sort of technology will eventually be used to overcome even complex problems such as Alzheimer’s disease and acquired immunodeficiency syndrome (AIDS).
One of the most unusual and potentially rewarding applications of DNA structure was introduced by computer scientist Leonard Adleman in 1994. Adleman devised a way to use short pieces of single-stranded DNA in solution as a rudimentary “computer” to solve a relatively complicated mathematical problem. By devising a code in which each piece of DNA stood for a specific variable in his problem and then allowing these single-stranded DNA pieces to base pair with each other randomly in solution, Adleman obtained an answer to his problem in a short amount of time. Soon thereafter, other computer scientists and molecular biologists began to experiment with other applications of this fledgling technology, which represents an exciting synthesis of two formerly separate disciplines. It may be that this research will prove to be the seed of another biological revolution with DNA at its center.
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