Deoxyribonucleic acid or DNA serves as the foundation for most genetic studies. In order to appreciate and understand a broad range of genetic principles, it will be essential to develop a working knowledge of DNA’s characteristics. With this in mind, we will use the first section of this chapter to lay some groundwork on DNA organization, structure, and duplication. This will be followed by coverage of related concepts such as ribonucleic acid (RNA) and protein synthesis, genetic control, mutations, and genetic recombination in the remaining five sections.
The Levels of Structure and Function of the Genome
The genome is the sum total of genetic material (DNA) carried within a cell. Although most of the genome exists in the form of chromosomes, genetic material can appear in nonchromosomal sites as well (figure 1). For example, bacteria and some fungi contain tiny extra pieces of DNA (plasmids), and the mitochondria and chloroplasts of eukaryotes are equipped with their own functional chromosomes. Genomes of cells are composed exclusively of DNA, but viruses contain either DNA or RNA as the principal genetic material.
Fig1. The general location and forms of the genome in two cell types and selected viruses (not to scale).
In general, a chromosome is a discrete cellular structure com posed of a neatly packaged DNA molecule. The chromosomes of eukaryotes and bacterial cells differ in several respects. The structure of eukaryotic chromosomes consists of a DNA molecule tightly wound around histone proteins, whereas a bacterial chromosome is condensed and secured into a packet by means of a different type of protein. Eukaryotic chromosomes are located in the nucleus; they vary in number from a few to hundreds; they can occur in pairs (diploid) or singles (haploid); and they are linear in format. In contrast, most bacteria have a single, circular chromosome, although some have multiple chromosomes and a few have linear chromosomes.
All chromosomes contain a series of basic informational units called genes. A gene can be defined from more than one perspective. In classical genetics, the term refers to the funda mental unit of heredity responsible for a given trait in an organism. In the molecular and biochemical sense, it is a portion of the chromosome that provides information for a given cell function. More specifically still, it is a specific segment of DNA that contains the necessary information to make a molecule of protein or RNA.
All of the genes in an organism constitute its distinctive genetic makeup, or genotype. The expression of the genotype creates traits (certain structures or functions) referred to as the phenotype. For example a person inherits a combination of genes (genotype) that gives a certain eye color or height (phenotype), a bacterium inherits genes that direct the formation of a flagellum or the ability to metabolize a certain substrate, and a virus has genes that dictate its capsid structure. All organisms contain more genes in their genotypes than are being seen as a phenotype at any given time. In other words, the phenotype can change depending on which genes are “turned on” or expressed.
The Size and Packaging of Genomes
Genomes vary greatly in size. Viruses have anywhere from a few to over a thousand genes; the bacterium Escherichia coli has a single chromosome containing 4,288 genes, and a human cell packs about five times that many into 46 chromosomes. What all genomes have in common is a sophisticated means of packaging that allows them to be reduced to about 1/1,000 of their original size (figure 2), allowing them to fit within the cell or nucleus.
Fig2. A disrupted Escherichia coli cell. The cell has ejected its unraveled chromosome, which now appears as thin strings radiating around the outer surface (10,000×). These strings are the uncoiled DNA strand, which is about 1,000 times longer than the cell for a typical bacterium. If laid end to end, the DNA of the 46 human chromosomes would stretch for six feet. Dr. Jack Griffith
The Packaging of DNA
Packing the mass of DNA into the cell in volves compacting the DNA molecule by means of supercoils or superhelices. In the simpler system of prokaryotes, the circular chromosome is packaged by the action of a special enzyme called a topoisomerase (specifically, DNA gyrase). This enzyme coils the chromosome into a tight bundle by introducing a reversible series of twists into the DNA molecule.
The system in eukaryotes is more complex, with three or more levels of coiling. First, the DNA molecule of a chromosome, which is linear, is wound twice around the histone proteins, creating a chain of nucleosomes. The nucleosomes fold in a spiral formation upon one another. An even greater supercoiling occurs when this spiral arrangement further twists on its radius into a giant spiral with loops radiating from the outside. This extreme degree of compactness is what makes the eukaryotic chromosome visible during mitosis (figure 3).
Fig3. Eukaryotic DNA interacts with a variety of proteins and small molecules. This relationship modulates the expression of many genes while at the same time allowing for the ordered condensation of DNA into a compact supermolecule.
The condensation of DNA and protein into chromatin was once thought to function mainly as a way to fit such a long molecule into a cell. However, it is now evident that the coiling of DNA also serves to make certain segments of the genetic program either more or less available. This action provides a major control on the ex pression of many traits, especially in eukaryotes. Having an additional regulatory function creates an alternative mechanism to guide when and how genes are accessed. The realization that the phenotype of a cell is due to more than just the order of nucleotides in the DNA (genotype) has led to a rethinking of some of the most basic concepts of genetics.
