4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar–Phosphate Backbone

DNA and RNA are linear polymers of a limited number of monomers. In DNA, the repeating units are nucleotides, with the sugar being a deoxyribose and the bases being adenine (A), thymine (T), guanine (G), and cytosine (C). In RNA, the sugar is a ribose and the base uracil (U) is used in place of thymine. DNA is the molecule of heredity in all prokaryotic and eukaryotic organisms. In viruses, the genetic material is either DNA or RNA.

4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure

All cellular DNA consists of two very long, helical polynucleotide strands coiled around a common axis. The sugar–phosphate backbone of each strand is on the outside of the double helix, whereas the purine and pyrimidine bases are on the inside stabilized by stacking forces. The two strands are held together by hydrogen bonds between pairs of bases: adenine is always paired with thymine, and guanine is always paired with cytosine. Hence, one strand of a double helix is the complement of the other. The two strands of the double helix run in opposite directions. Genetic information is encoded in the precise sequence of bases along a strand.

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DNA is a structurally dynamic molecule that can exist in a variety of helical forms: A-DNA, B-DNA (the classic Watson–Crick helix), and Z-DNA. In A-, B-, and Z-DNA, two antiparallel chains are held together by Watson–Crick base pairs and stacking interactions between bases in the same strand. A- and B-DNA are right-handed helices. In B-DNA, the base pairs are nearly perpendicular to the helix axis. Z-DNA is a left-handed helix. Most of the DNA in a cell is in the B-form.

Double-stranded DNA can also wrap around itself to form a supercoiled structure. The supercoiling of DNA has two important consequences. Supercoiling compacts the DNA and, because supercoiled DNA is partly unwound, it is more accessible for interactions with other biomolecules.

Single-stranded nucleic acids, most notably RNA, can form complicated three-dimensional structures that may contain extensive double-helical regions that arise from the folding of the chain into hairpins.

4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information

The structural nature of the double helix readily accounts for the accurate replication of genetic material because the sequence of bases in one strand determines the sequence of bases in the other strand. In replication, the strands of the helix separate and a new strand complementary to each of the original strands is synthesized. Thus, two new double helices are generated, each composed of one strand from the original molecule and one newly synthesized strand. This mode of replication is called semiconservative replication because each new helix retains one of the original strands.

In order for replication to take place, the strands of the double helix must be separated. In vitro, heating a solution of double-helical DNA separates the strands, a process called melting. On cooling, the strands reanneal and re-form the double helix. In the cell, special proteins temporarily separate the strands in replication.

4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates

In the replication of DNA, the two strands of a double helix unwind and separate as new strands are synthesized. Each parent strand, with the help of a primer, acts as a template for the formation of a new complementary strand. The replication of DNA is a complex process carried out by many proteins, including several DNA polymerases. The activated precursors in the synthesis of DNA are the four deoxyribonucleoside 5′-triphosphates. The new strand is synthesized in the 5′ → 3′ direction by a nucleophilic attack by the 3′-hydroxyl terminus of the primer strand on the innermost phosphorus atom of the incoming deoxyribonucleoside triphosphate. Most important, DNA polymerases catalyze the formation of a phosphodiester linkage only if the base on the incoming nucleotide is complementary to the base on the template strand. In other words, DNA polymerases are template-directed enzymes. The genes of some viruses, such as tobacco mosaic virus, are made of single-stranded RNA. An RNA-directed RNA polymerase mediates the replication of this viral RNA. Retroviruses, exemplified by HIV-1, have a single-stranded RNA genome that undergoes reverse transcription into double-stranded DNA by reverse transcriptase, an RNA-directed DNA polymerase.

4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules

The flow of genetic information in normal cells is from DNA to RNA to protein. The synthesis of RNA from a DNA template is called transcription, whereas the synthesis of a protein from an RNA template is termed translation. Cells contain several kinds of RNA, among which are messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), which vary in size from 75 to more than 5000 nucleotides. All cellular RNA is synthesized by RNA polymerases according to instructions given by DNA templates. The activated intermediates are ribonucleoside triphosphates and the direction of synthesis, like that of DNA, is 5′ → 3′. RNA polymerase differs from DNA polymerase in not requiring a primer.

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4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point

The genetic code is the relation between the sequence of bases in DNA (or its RNA transcript) and the sequence of amino acids in proteins. Amino acids are encoded by groups of three bases (called codons) starting from a fixed point. Sixty-one of the 64 codons specify particular amino acids, whereas the other 3 codons (UAA, UAG, and UGA) are signals for chain termination. Thus, for most amino acids, there is more than one code word. In other words, the code is degenerate. The genetic code is nearly the same in all organisms. Natural mRNAs contain start and stop signals for translation, just as genes do for directing where transcription begins and ends.

4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons

Most genes in higher eukaryotes are discontinuous. Coding sequences in these split genes, called exons, are separated by noncoding sequences, called introns, which are removed in the conversion of the primary transcript into mRNA and other functional mature RNA molecules. Split genes, like continuous genes, are colinear with their polypeptide products. A striking feature of many exons is that they encode functional domains in proteins. New proteins probably arose in the course of evolution by the shuffling of exons. Introns may have been present in primordial genes but were lost in the evolution of such fast-growing organisms as bacteria and yeast.