The principles of inheritance were first established in 1866 by Gregor Mendel based on careful observations of the outcomes of crossing garden peas with different characteristics, e.g., flower color. Studies performed in 1928 by Fred Griffith, an English microbiologist, demonstrated that when heat-killed bacteria are mixed with live bacteria the characteristics of the living organisms could change. The pathogenicity of Diplococcus pneumoniae is dependent on the possession of a polysaccharide capsule, and the ability to synthesize a capsule can be transferred to nonpathogenic strains by a substance present in pathogenic strains that have been killed by heat. That a nucleic acid, deoxyribonucleic acid (DNA), was this “genetic transforming factor” was demonstrated by the studies of Avery et al. (1) reported in 1944.

A nucleic acid is composed of a pentose sugar linked to a phosphate group and a nitrogenous base. The pentose sugar in DNA is 2-deoxyribose, whereas the pentose in ribonucleic acid (RNA) is ribose (Fig. 7.1). Either of four different bases can be linked to the carbon at ring position 1 of deoxyribose: thymine (T), adenine (A), cytosine (C), and guanine (G). Uracil (U) is found in place of T attached to ribose. A and G are purines with a double-ring structure, whereas C, U, and T are pyrimidines and have a single-ring structure (Fig. 7.2). Nucleosides (pentose plus a base) can be phosphorylated by the addition of a phosphate group on the 3′ or 5′ carbon to become a nucleotide. Adenosine 5′-triphosphate, a very important molecule in metabolism and energy transfer, has three phosphate groups added to the carbon at position 5 (Fig. 7.1).

A sugar-phosphate chain is formed by the linking of the pentose sugars together by a phosphate group, the 5′ carbon of one sugar linked to the 3′ carbon of the adjacent sugar by a phosphodiester bond (Fig. 7.2).

DNA forms a double helix, with two chains or strands intertwined in an antiparallel direction, i.e., one strand running in the 5′ to 3′ direction and the other strand in the opposite direction (Fig. 7.2). The sugar-phosphate backbone is on the outside of the helix, and the base groups are directed toward the inside of the helix. The base groups of one strand associate by hydrogen bonding in a specific manner with the base groups of the other strand. A always bonds to T, and G always bonds to C; this association is termed complementary base pairing. A purine (two rings) also always bonds to a pyrimidine (one ring), thus keeping the diameter of the double helix constant.

The association between the two strands of DNA is not permanent. When DNA is replicated, the strands are unwound and separated region by region by an enzyme called a topoisomerase. A new daughter strand is synthesized alongside each of the original single parent strands by assembly of nucleotides by complementary base pairing. The formation of phosphodiester bonds links the nucleotides together into a complementary chain by the action of an enzyme called DNA polymerase, which always synthesizes the new chain in the 5′ to 3′ direction. This form of replication is called semiconservative because each of the new double-stranded molecules contains an old and a new single strand (Fig. 7.3). As the unwound region of DNA moves along the strand forming a replication fork, the daughter DNA
must be synthesized on one strand in segments (DNA polymerase synthesizes always in the 5′ to 3′ direction). These fragments are then covalently bonded together and are called Okazaki fragments.