The gene is the unit of \Theredity\t. Along with many other such units, it is transmitted from parents to offspring. Each gene, acting either alone or with genes, determines one or more characteristics of the resulting organism. The totality of genes that make up the heredity constitution of an organism is called a \Tgenome\t. Genes occur in strands of genetic material called chromosomes (see \Tgenetics\t). In most cells each gene occupies a particular position within a specific chromosome. Chromosomes can break, however, and some of their genes may be transferred either to places on the same chromosome or to other chromosomes. When this happens, new combinations (recombinants) of the gene are formed. Genes can also change in chemical composition. In their altered recombinant or chemically varied form, they produce different elements from the unaltered genes (see \Tmutation\t). Depending on the characteristics transmitted by the gene, the environment may also play an important role in determining the extent to which the gene's potential effect is realized (see \Tgene bank\t). THE NATURE OF THE GENE The subdivision of genetics concerned with the structure and functioning of genes at the molecular level is called molecular genetics. Since the term gene was first proposed by the Danish geneticist Wilhelm Johannsen in 1909, concepts of the nature of the gene have undergone modification. Current understanding of gene structure and function at the molecular level had its origin in 1944, with the work of Canadian bacteriologist Oswald T. \TAvery\t and American scientist Colin M. \TMacLeod\t and Maclyn McCARTY. They showed that the genes of bacteria are composed of the chemical compound called deoxyribonucleic acid, or \TDNA\t. This was later found to be true of the genes of most other organisms. A further advance was made in 1953, when American biochemist James D. \TWatson\t and English scientist Francis \TCrick\t jointly presented their model of the structure of the \TDNA\t molecule. The molecule was shown to consist of two chains of chemical compounds called polynucleotides, the chains between twisted into the form of a coil, or double helix. Subsequently, in 1961, U. S. biochemist M. W. \TNirenberg\t and others figured out the relationship between the composition of \TDNA\t and the composition of the proteins produced by genes. This relationship is known as the \Tgenetic code\t. It later became evident that another nucleic acid, called ribonucleic acid, or \TRNA\t, also functions to carry out protein synthesis. At first it was thought that all genes functioned in an identical manner to produce the various characteristics of an organism. Three different classes of genes, however, are now recognized. One class consists of the structural genes, whose genetic codes determine the sequences of \Lamino acid\ls that go to make up proteins or the smaller molecules known as polypeptides (see \Tpeptide\t), including many hormones. Another class of genes has genetic codes that specify molecules that function in the physical and chemical processes involved in \Tprotein\t \Lsynthe\lsis. The third gene class consists of regulatory genes, which are noncoding. They act solely as "recognition" sites for enzymes and other proteins involved in controlling protein synthesis (see \Toperon\t). Early studies seemed to indicate that a gene, wherever it happened to be located within a chromosome, consisted of a single continuous unit. Later it was found some genes have a region called the leader that precedes the coding segment, and a region called the trailer that follows it. In addition, the coding segment itself may actually be broken up into sections, with intervening coding portions called exons. A far-reaching advance in gene study was made in 1973, when American geneticists Stanley Cohen and Herbert Boyer demonstrated that certain enzymes, called restriction endonucleases, could be used to make cuts in a \TDNA\t molecule at certain specific sites. This produced a series of segments with identical free ends, which could join with other free ends having the appropriate complementary configuration. The result was the reestablishment of a fully functional \TDNA\t double helix. Using this procedure, called gene splicing (see \Tgenetic engineering\t), it became possible to take a gene from a human cell and transfer it to a bacterium, mouse, rat, or pig, where the human gene would functions as it would in a human being. It even became possible to transfer animal genes to plants. One projected use of this procedure would be to transfer appropriate normal human genes to cells of individuals suffering from hemophilia, cystic fibrosis, or other \Tgenetic diseases\t. Should such transfers provide successful, they could provide a means to cure such genetic diseases through direct gene therapy. The actual functioning of genes is complex. To understand it, the nature and structure of the nucleus acids \TDNA\t and \TRNA\t must be examined in greater detail. DNA \TDNA\t occurs as the genetic material in most viruses and in all cellular organisms. Some viruses, however, have no \TDNA\t. Instead, their genetic material is in the form of \TRNA\t. Depending on the particular \TDNA\t-containing organisms, most \TDNA\t is found either in a single chromosome, as in bacteria, blue-green algae, and \TDNA\t viruses, or in several chromosomes, as in all other living things. In addition to its presence in chromosomes, \TDNA\t is also found in many \Tcell\t organelles, such as plasmids in bacteria, chloroplasts in plants, and mitochondria in both plants and animals. Structure All \TDNA\t molecules consist of a linked series of units that are called nucleotides. Each \TDNA\t nucleotide is composed of three subunits: a 5-carbon sugar called deoxyribose, a phosphate group that is joined to one end of the sugar molecule,and one of several different nitrogen-containing bases linked to the opposite end of the sugar molecule. The four bases that predominate in \TDNA\t are called adenine and guanine (double-ringed \Tpurine\t compounds), and thymine and cytosine (single-ringed \Tpyrimidine\t compounds). Four different types of \TDNA\t nucleotides can be formed, depending on the base involved. The phosphate group of each nucleotide bonds to one of the carbon atoms of the sugar molecule in the adjacent nucleotide. This forms a so-called polynucleotide chain. The \TDNA\t of most organisms consists of two polynucleotide chains that are coiled to form a double helix. The backbone, or outside margin, of each chain consists of the sugar-phosphate sequence. The bases project inward from this backbone, into the helix. The bases of one chain are attracted to bases on the other chain by means of hydrogen bonds. This holds the double helix together. Exceptions to this type of structural organization are found in some viruses with genetic material consisting of a single \TDNA\t chain. In a \TDNA\t double helix the pairing between bases of the two chains is highly specific. That is, adenine is always linked to thymine by two hydrogen bonds, and guanine is always linked to crystosine by three hydrogen bonds. This arrangement--a purine linked to a pyrimidine--results in a molecule of uniform diameter. Because of this specific way in which \TDNA\t nucleotides are paired through certain pairs of bases, the base sequence of the two strands in the helix is said to be complementary. This means that the base sequence of either strand may be converted to that of its partner by replacing adenine by thymine or thymine by adenine, and replacing guanine by cytosine or cytosine by guanine. Functions The genetic material \TDNA\t has two specific functions. It provides for protein synthesis and hence for the growth development of an organism. It also furnishes all descendants of the organism with protein-synthesizing information by replicating itself and passing a copy to each offspring. This information, known as the genetic code, lies in the sequence of bases of \TDNA\t, which specifies the sequence of amino acids in a protein. \TDNA\t does not act directly in the process of protein synthesis. Instead it acts through the formation of a particular type of \TRNA\t called the messenger \TRNA\t (m\TRNA\t) during the process of transcription. \TDNA\t replication depends on the principle of complementarity mentioned above. During the process of replication, the two strands of \TDNA\t double helix separate from one another. As separation occurs, each base on each strand attracts its complementary base-containing nucleotide, to which it becomes attached by hydrogen bonds. For example, the base adenine attracts and bonds to the base thymine. As the complementary nucleotides are fitted into place, an enzyme called \TDNA\t polymerase performs its function. It binds the phosphate of one nucleotide to the sugar molecule of the adjacent nucleotide, forming a new polynucleotide chain. The new strand of \TDNA\t remains hydrogen-bonded to the old one, and together they form a new double-helix molecule. This type of replication is called semiconservative, because each newly formed double-stranded molecule consists of one previously existing \TDNA\t strand. Viruses, which contain single-stranded \TDNA\t, replicate by a slightly more complicated process. When a virus enters a cell, it makes a complementary copy of itself, to which it remains attached. A virus in this condition is said to be in its replicative form (RF), temporarily becoming a double-stranded \TDNA\t virus. The two chains separate during replication, but only the one recently formed strand attracts complementary nucleotides. These newly attracted nucleotides are joined together by the enzyme \TDNA\t polymerase, their base sequence being exactly the same as that of the original \TDNA\t virus. The newly formed polynucleotide chain is released from the RF of the original virus and functions alone. Mutations Many environmental factors can alter the structure of a \TDNA\t molecule. Some factors may be physical, and others are chemical. A mutation occurs when such alterations lead to permanent change in the base sequence of a \TDNA\t molecule. Mutations in turn result in an inherited change in protein synthesis. Most mutations tend to be harmful in their effects, and a number of self-repair mechanisms exist to deal with the damage done to \TDNA\t by environmental factors. Processes of mutation and self-repair have been studied, for example, in the case of damage caused to \TDNA\t by exposure to ultraviolet (UV) light. The energy absorbed by \TDNA\t during UV exposure results in the formation of chemical bonds between adjacent bases of the same polynucelotide strand. This condition interferes with base pairing during replication and leads to mutations. RNA Ribonucleic acid, or \TRNA\t, is needed in all organisms in order for protein synthesis to occur. It is also the genetic material of some viruses, which are referred to as \TRNA\t viruses (see \Tvirus\t). Like \TDNA\t, all \TRNA\t molecules have a similar chemical organization consisting of nucleotides. Each \TRNA\t nucleotide, like those in \TDNA\t, consists of three subunits. One is a 5-carbon sugar called ribose, the second is a phosphate group that is attached to one end of the sugar molecule, and the third is one of several different nitrogen-containing bases linked to the opposite end of the sugar molecule. Four bases predominate in \TRNA\t: adenine and guanine (double-ringed purine compounds), and uracil and cytosine (single-ringed pyrimidine compounds). Structure \TRNA\t differs from \TDNA\t in two aspects of its chemical organization. First, the sugar in \TRNA\t is of the ribose type, indicating that the second carbon molecule in the ring has a hydroxyl (OH) group attached to it. (In \TDNA\t the second carbon in the ring has only a hydrogen (H) atom--hence the prefix deoxy, meaning "lacking oxygen," in the \TDNA\t sugar deoxyribose.) Second, the base uracil is present only in \TRNA\t. (Thymine, the base comparable to uracil, is present only in \TDNA\t.) Both bases are single-ringed pyrimidines, and their nucleotides substitute for one another, depending on whether the strand is \TRNA\t or \TDNA\t. The nucleotides of \TRNA\t are joined in a polynucleotide chain by means of bonding the phosphate of each nucleotide to a carbon atom of the adjacent nucleotide's sugar subunit. In \TRNA\t viruses the \TRNA\t is in the form of either a double or a single polynucleotide chain. In double-stranded \TRNA\t versus, the geometric arrangement of the two polynucleotide chains is similar to that of double-stranded \TDNA\t, and the pairing between bases of the two \TRNA\t chains is highly specific. Adenine is always linked to cytosine by three hydrogen bonds. Again as in \TDNA\t, the specific pairing of \TRNA\t nucleotides according to the base concerned indicates that the base sequence of the two \TRNA\t strands is complementary. Thus if the base sequence of one strand is known, then the base sequence of the other strand can be specified. Functions Replication of double-stranded \TRNA\t follows the pattern described for \TDNA\t. The \TRNA\t chains separate, and each base attracts an \TRNA\t nucleotide carrying the complementary base, to which it is attached by hydrogen bonds. As the complementary nucelotides are fitted into place, an enzyme called \TRNA\t replicase binds the nucleotides together, forming a new polynucleotide chain. The new strand of \TRNA\t remains hydrogen-bonded to the old strand--another example of semiconservative replication. Single-strand \TRNA\t viruses fall into two classes. The first group includes the polio virus that attracks the nerve cells of humans and other primates. When this type of virus enters a cell, the virus makes a complementary copy of itself, to which it remains attached. In this stage the virus is again said to be in its RF form, temporarily becoming a double-stranded \TRNA\t virus. During replication, although the two chains separate, only the recently formed strand attracts nucleotides with complementary bases. The newly attracted nucleotides are joined together by the enzyme \TRNA\t replicase. In their base sequence they are exactly the same as the original \TRNA\t virus. The newly formed chain is released from the RF of the original virus to function independently. The second group of single stranded \TRNA\t viruses contains some that causes tumors in animals, such as mouse leukemia virus and mouse mammary tumor virus. Upon entering a cell, this type of virus makes a complementary strand of itself. This newly formed chain, however, is composed of \TDNA\t nucleotides. The single strand of \TDNA\t in turn makes a complementary \TDNA\t strand of itself, forming a \TDNA\t double helix. The newly formed \TDNA\t double helix becomes incorporated into one of the chromosomes of the host cell, where it is replicated along with the host \TDNA\t. While in the host cell, the \TRNA\t-derived viral \TDNA\t produces single-strand \TRNA\t viruses that leave the host cell and enter other cells. The enzyme involved in making a \TDNA\t complement of \TRNA\t is called \TRNA\t-directed \TDNA\t polymerase, or reverse transcriptase--a name based on the action of reversing the transcription process. Such viruses are also referred to as \Lretrovirus\les. One of them, called HIV (for human immunodeficiency virus), invades and kills the T-helper lymphocytes of a person's immune system, resulting in the disease called acquired immune deficiency syndrome, or \TAIDS\t (see \TAIDS\t). Types of \TRNA\t \TRNA\t that is involved in protein synthesis is single-stranded. It belongs to one of three distinct types, called ribosomal \TRNA\t (r\TRNA\t), transfer \TRNA\t (t\TRNA\t), and messenger \TRNA\t (m\TRNA\t). A cell's ribosomal \TRNA\t is associated with protein, forming bodies called \Lribosome\ls. Ribosomes are sites of protein synthesis. Ribosomal \TRNA\t varies in size and constitutes 85 to 90 percent of all the \TRNA\t in a cell. Transfer \TRNA\t, also called soluble \TRNA\t or adapter \TRNA\t, is a group of small molecules, each of which has a specific attraction for one of the amino acids. The function of each type of t\TRNA\t is to bring its specific amino acid to a ribosome for possible inclusion in the particular protein being synthesized. The t\TRNA\t molecules, about 80 nucleotides in a cloverleaf pattern, constitute about 5 percent of a cell's \TRNA\t. The third type of cellular \TRNA\t, messenger \TRNA\t, constitutes 5 to 10 percent of a cell's total \TRNA\t. It acts as an intermediary between the genes located in the chromosomes, and the ribosomes located in the cytoplasm. As its name implies, m\TRNA\t carries the genetic code contained in the sequence of bases in the cell's \TDNA\t. Because the DNAs from various organisms differ only in the sequence of their bases, m\TRNA\t from different organisms must reflect this difference in base sequence. The synthesis of m\TRNA\t, called transcription, involves the formation of an \TRNA\t chain that is complementary to one of the two strands of a \TDNA\t double helix. In the transcription process, only nucleotides that contain ribose are used. In this process, uracil acts as the complement of adenine. The enzyme involved in transcription is known as \TRNA\t polymerase. \TRNA\t as an Information Molecule The earliest information molecule to have evolved must have been both relatively simple in structure and capable of enzymatic activity. \TRNA\t, which acts as the carrier of genetic messages in all organisms, is the simplest molecule known that has the capacity to store and transmit information. Initially, evidence that \TRNA\t can also act as a catalyst of reactions centered on the enzyme called ribonuclease P, which consists of protein and \TRNA\t. The enzyme has been found on virtually all organisms. It is involved in the process that transforms the precursor molecules of tRNAs into their fully functional forms. Geneticists have since discovered that the \TRNA\t component of this enzyme, acting alone, can perform the catalytic activity of the enzyme, whereas the protein alone cannot. More recently, investigations have concentrated on the ribosomal-\TRNA\t specifying gene of the protozoan Tetrahymena thermophila. This gene consists of a noncoding sequence, or intron, between two coding portions, or exons. After transcription, the precursor \TRNA\t molecule has to have the intron-transcribed segment removed before the ribosomal-\TRNA\t molecule can become functional. The intron specified segment snips itself out of the precursor molecule and splices the loose ends together to form the functional molecule. These findings, that \TRNA\t is capable of catalytic activity, lend support to the concept that \TRNA\t was indeed the earliest information molecule, and that \TDNA\t must have evolved from \TRNA\t. Support for this hypothesis is found in the life cycles of \TRNA\t tumor viruses, which, upon entering cells, make \TDNA\t copies of themselves. Louis Levine Bibliography: Alberts, Bruce, et al., Molecular Biology of the Cell (1983); Dawkins, Richard, The Selfish Gene (1989); Hames, B.D., and Glober, D.M., Transcription and Splicing (1988); Juma, Calestous, The Gene Hunters (1989); Kornberg, Arthur, \TDNA\t Replication (1980); Suzuki, D.T., et al., An Introduction to Genetics (1986); Watson, J.D., et al., The Molecular Biology of the Gene, 2 vols. (1987).