chapter 9 Nucleic acids: biological molecules for information storage, retrieval and usage

KEY POINTS

Nucleic acids are used to store and to utilise genetic information.

There are two distinct types: DNA and RNA.

DNA is present as chromosomes in the nucleus of eukaryotic cells.

DNA is made from subunits called deoxyribonucleotides.

DNA is usually found as a double helix made from two molecules of DNA.

RNA is present in many cellular compartments.

RNA is a polymer of ribonucleotides.

RNA is usually single stranded.

RNA is found as three major forms in cells: messenger RNA, transfer RNA and ribosomal RNA, all of which are involved in protein synthesis.

Nucleic acids were first discovered by Friedrich Miescher in 1871. Miescher identified a phosphate-rich cellular substance from the nucleus of white blood cells that he called ‘nuclein’. It was later discovered that nucleic acids are macromolecules synthesised by the polymerisation of monomeric subunits known as nucleotides, with a sugar-phosphate backbone linked by ester bonds. Nucleic acids are primarily involved in the storage and expression of the genetic information of the cell, but also play structural roles. In cells the two forms are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). At least one form of nucleic acid is found in all living things, including all cells and viruses. The discovery of the structure of DNA by Crick, Watson and Wilkins, who received a Nobel Prize in 1962, has been heralded as one of the most important scientific discoveries of the twentieth century.

The general structure of nucleic acids

Nucleotides are composed of a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar (either deoxyribose or ribose) and a phosphate group. In DNA the sugar used is 2-deoxyribose whereas RNA contains ribose (the only difference is the presence of an extra hydroxyl group at the 2′ position on the ring). There is also a slight difference in the nitrogenous bases found in the two types of nucleic acid. Adenine, cytosine and guanine are found in both types while thymine occurs only in DNA and uracil is found only in RNA.

Nucleic acids can be either single-stranded or double-stranded. A double-stranded nucleic acid consists of two single-stranded nucleic acid molecules held together by hydrogen bonds, such as in the DNA double helix. In contrast, RNA is usually single stranded, but any given strand may fold back upon itself to form secondary structure as in transfer ribonucleic acid (tRNA) and ribosomal ribonucleic acid (rRNA). Within cells, DNA is usually double-stranded, though some viruses have single-stranded DNA as their genome, and retroviruses use single-stranded RNA for their genome.

The sugars and phosphates in nucleic acids are connected to each other in an alternating chain (the backbone), linked by shared oxygen atoms, forming phosphodiester bonds. The carbons that are linked to the phosphate groups are referred to as the 3′ and the 5′ carbons of the sugar. This gives nucleic acids polarity since one end of the chain carries a phosphate group (the 5′ end) while the other end has a free hydroxyl group (the 3′ end). The bases are attached to the 1′ carbon of the pentose sugar ring.

Types of nucleic acids

Deoxyribonucleic acid (DNA) carries the genetic instructions used in the growth, development and functioning of all known living organisms. There are viruses that use ribonucleic acid (RNA) as their genetic information store but it is debatable whether or not viruses are considered to be living organisms. However, the primary role of DNA is the long-term storage of information for the production of cellular components such as proteins and RNA molecules. The information is stored in discrete units called genes. Genes are surrounded by other DNA sequences that are involved in controlling the use of this genetic information, and they can also play structural roles. DNA contains four types of bases (cytosine, thymine, guanine and adenine) that are attached to the sugars in the sugar-phosphate backbone to form long chains. The most common form of DNA contains two molecules coiled around each other to form a double helix.

RNA consists of a chain of nucleotide monomers and plays several important roles in the translation of genetic information stored in DNA into proteins. RNA carries the information stored in DNA to sites of protein synthesis, forms part of the structure of ribosomes and delivers activated amino acids for use in protein synthesis. There are three main types of RNA:

• transfer RNA (tRNA)

• messenger RNA (mRNA)

• ribosomal RNA (rRNA)

The building blocks of nucleic acids

Bases in nucleic acids are a family of nitrogenous heterocyclic aromatic compounds (Fig 9-1). Cytosine (C), guanine (G), adenine (A) and thymine (T) are found in DNA, whereas uracil (U) replaces thymine in RNA. All bases can be classified into two groups based on their skeletal structure. Adenine and guanine are based on purine, a molecule that contains two rings, and are referred to as purine bases whereas cytosine, thymine and uracil are referred to as pyrimidine bases, being based on pyrimidine, a single-ring molecule.

FIGURE 9-1 The structures of the major bases found in nucleic acids. The bases can be divided into two families based on the number of rings in their structure. The pyrimidine bases have a single ring, with cytosine and thymine being found in DNA. In RNA the thymine is replaced by uracil. The other family, the purines, have a structure based on two rings, and consist of adenine and guanine which are found in both DNA and RNA.

Nucleosides are made by attaching a base to one of the sugars, either ribose or deoxyribose. They are named by modifying the name of the base they contain. Thus, the four nucleosides based on ribose are adenosine, guanosine, cytidine and uridine, and the four nucleosides based on deoxyribose are deoxyadenosine, deoxyguanosine, deoxycytidine and deoxythymine.

Nucleotides are made by adding a phosphate group to a nucleoside (Fig 9-2). They are used as the monomers in RNA and DNA, but are also components of important enzyme cofactors (see Ch 15), such as coenzyme A (CoA), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP) and adenosine triphosphate (ATP). They can also play important roles in other cellular processes such as signalling between or within cells. They are named by modifying the name of the nucleoside they contain together with the number of phosphates they contain. Thus, adenine attached to ribose forms the nucleoside adenosine. Addition of a phosphate to adenosine forms adenosine monophosphate. As further phosphates are added, adenosine diphosphate and then adenosine triphosphate are formed.