Nucleic Acids

If the primary structure of polypeptides determines the conformation of a protein, what determines primary structure? The amino acid sequence of a polypeptide is programmed by a unit of inheritance known as a gene. Genes consist of DNA, which is a polymer belonging to the class of compounds known as nucleic acids.

The Roles of Nucleic Acids

There are two types of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) . These are the molecules that enable living organisms to reproduce their complex components from one generation to the next. Unique among molecules, DNA provides directions for its own replication. DNA also directs RNA synthesis and, through RNA, controls protein synthesis.

The figure above shows DNA → RNA → protein: a diagrammatic overview of information flow in a cell. In a eukaryotic cell, DNA in the nucleus programs protein production in the cytoplasm by dictating the synthesis of messenger RNA (mRNA), which travels to the cytoplasm and binds to ribosomes. As a ribosome (greatly enlarged in this drawing) moves along the mRNA, the genetic message is translated into a polypeptide of specific amino acid sequence.

DNA is the genetic material that organisms inherit from their parents. Each chromosome contains one long DNA molecule, usually consisting of from several hundred to more than a thousand genes. When a cell reproduces itself by dividing, its DNA molecules are copied and passed along from one generation of cells to the next. Encoded in the structure of DNA is the information that programs all the cell’s activities. The DNA, however, is not directly involved in running the operations of the cell, any more than computer software by itself can print a bank statement or read the bar code on a box of cereal. Just as a printer is needed to print out a statement and a scanner is needed to read a bar code, proteins are required to implement genetic programs. The molecular hardware of the cell—the tools for most biological functions—consists of proteins. For example, the oxygen carrier in the blood is the protein hemoglobin, not the DNA that specifies its structure.

How does RNA, the other type of nucleic acid, fit into the flow of genetic information from DNA to proteins? Each gene along the length of a DNA molecule directs the synthesis of a type of RNA called messenger RNA (mRNA). The mRNA molecule then interacts with the cell’s protein–synthesizing machinery to direct the production of a polypeptide. We can summarize the flow of genetic information as DNA → RNA → protein (see Figure 5.25). The actual sites of protein synthesis are cellular structures called ribosomes. In a eukaryotic cell, ribosomes are located in the cytoplasm, but DNA resides in the nucleus. Messenger RNA conveys the genetic instructions for building proteins from the nucleus to the cytoplasm. Prokaryotic cells lack nuclei, but they still use RNA to send a message from the DNA to the ribosomes and other equipment of the cell that translate the coded information into amino acid sequences.

The Structure of Nucleic Acids

Nucleic acids are macromolecules that exist as polymers called polynucleotides.

The components of nucleic acids. (a) A polynucleotide has a regular sugar–phosphate backbone with variable appendages, the four kinds of nitrogenous bases. RNA usually exists in the form of a single polynucleotide, like the one shown here. (b) A nucleotide monomer is made up of three components: a nitrogenous base, a sugar, and a phosphate group, linked together as shown here. Without the phosphate group, the resulting structure is called a nucleoside. (c) The components of the nucleoside include a nitrogenous base (either a purine or a pyrimidine) and a pentose sugar (either deoxyribose or ribose).

As indicated by the name, each polynucleotide consists of monomers called nucleotides . A nucleotide is itself composed of three parts: a nitrogenous base, a pentose (five–carbon sugar), and a phosphate group (Figure 5.26b). The portion of this unit without the phosphate group is called a nucleoside.

The DNA double helix and its replication. The DNA molecule is usually double–stranded, with the sugar–phosphate backbone of the antiparallel polynucleotide strands (symbolized here by blue ribbons) on the outside of the helix. Holding the two strands together are pairs of nitrogenous bases attached to each other by hydrogen bonds. As illustrated here with symbolic shapes for the bases, adenine (A) can pair only with thymine (T), and guanine (G) can pair only with cytosine (C). When a cell prepares to divide, the two strands of the double helix separate, and each serves as a template for the precise ordering of nucleotides into new complementary strands (orange). Each DNA strand in this figure is the structural equivalent of the polynucleotide diagrammed in Figure 5.26a.

The DNA Double Helix

The RNA molecules of cells consist of a single polynucleotide chain like the one shown in Figure 5.26. In contrast, cellular DNA molecules have two polynucleotides that spiral around an imaginary axis, forming a double helix (Figure 5.27).

Figure 5.27 The DNA double helix and its replication. The DNA molecule is usually double–stranded, with the sugar–phosphate backbone of the antiparallel polynucleotide strands (symbolized here by blue ribbons) on the outside of the helix. Holding the two strands together are pairs of nitrogenous bases attached to each other by hydrogen bonds. As illustrated here with symbolic shapes for the bases, adenine (A) can pair only with thymine (T), and guanine (G) can pair only with cytosine (C). When a cell prepares to divide, the two strands of the double helix separate, and each serves as a template for the precise ordering of nucleotides into new complementary strands (orange). Each DNA strand in this figure is the structural equivalent of the polynucleotide diagrammed in Figure 5.26a.

James Watson and Francis Crick, working at Cambridge University, first proposed the double helix as the three–dimensional structure of DNA in 1953. The two sugar–phosphate backbones run in opposite 5′ → 3′ directions from each other, an arrangement referred to as antiparallel, somewhat like a divided highway. The sugar–phosphate backbones are on the outside of the helix, and the nitrogenous bases are paired in the interior of the helix. The two polynucleotides, or strands, as they are called, are held together by hydrogen bonds between the paired bases and by van der Waals interactions between the stacked bases. Most DNA molecules are very long, with thousands or even millions of base pairs connecting the two chains. One long DNA double helix includes many genes, each one a particular segment of the molecule.

Only certain bases in the double helix are compatible with each other. Adenine (A) always pairs with thymine (T), and guanine (G) always pairs with cytosine (C). If we were to read the sequence of bases along one strand as we traveled the length of the double helix, we would know the sequence of bases along the other strand. If a stretch of one strand has the base sequence 5′–AGGTCCG–3′, then the base–pairing rules tell us that the same stretch of the other strand must have the sequence 3′–TCCAGGC–5′. The two strands of the double helix are complementary, each the predictable counterpart of the other. It is this feature of DNA that makes possible the precise copying of genes that is responsible for inheritance (see Figure 5.27). In preparation for cell division, each of the two strands of a DNA molecule serves as a template to order nucleotides into a new complementary strand. The result is two identical copies of the original double–stranded DNA molecule, which are then distributed to the two daughter cells. Thus, the structure of DNA accounts for its function in transmitting genetic information whenever a cell reproduces.

DNA and Proteins as Tape Measures of Evolution

We are accustomed to thinking of shared traits, such as hair and milk production in mammals, as evidence of shared ancestors. Because we now understand that DNA carries heritable information in the form of genes, we can see that genes and their products (proteins) document the hereditary background of an organism. The linear sequences of nucleotides in DNA molecules are passed from parents to offspring; these sequences determine the amino acid sequences of proteins. Siblings have greater similarity in their DNA and proteins than do unrelated individuals of the same species. If the evolutionary view of life is valid, we should be able to extend this concept of “molecular genealogy” to relationships between species: We should expect two species that appear to be closely related based on fossil and anatomical evidence to also share a greater proportion of their DNA and protein sequences than do more distantly related species. In fact, that is the case. For example, if we compare a polypeptide chain of human hemoglobin with the corresponding hemoglobin polypeptide in five other vertebrates, we find the following. In this chain of 146 amino acids, humans and gorillas differ in just 1 amino acid, humans and gibbons differ in 2 amino acids, and humans and rhesus monkeys differ in 8 amino acids. More distantly related species have chains that are less similar. Humans and mice differ in 27 amino acids, and humans and frogs differ in 67 amino acids. Molecular biology has added a new tape measure to the toolkit biologists use to assess evolutionary kinship.