The chemical building blocks of nucleic acid are called nucleotides, and every nucleotide contains a nitrogenous base. The bases can be viewed as the most significant components of nucleic acids such as DNA and RNA, as they are the only variant elements in these otherwise monotonously repeating polymers. Consequently, it is the arrangement of bases along DNA strands that contains the genetic information coding for proteins. This is transcribed into the complementary base sequence in RNA and translated into the amino acid sequences of the protein chains, with three bases specifying a single amino acid. Thus the coding potential of the nucleic acid bases is arranged as a triplet code.
The bases are classified as purines and pyrimidines. Purines are two ring shaped molecules joined together, one with six and one with five atoms, while pyrimidines are single rings of six atoms. DNA is made up of nucleotides containing one of four different bases: adenine, guanine, cytosine and thymine. These are frequently symbolized by their single letter abbreviations A, G, C and T respectively. A and G belong to the two ringed purine class while C and G are pyrimidines. RNA also contains four different bases. Three of these, adenine, guanine and cytosine are the same as in DNA but RNA contains the purine base uracil (U) instead of thymine.
Purine and pyrimidine bases on opposite DNA strands bond in a geometrically complementary manner to form the classic Watson-Crick base pairing. Even though other interactions are theoretically possible, there are only two types of base pairs commonly found in natural DNA: adenine with thymine (A:T) and cytosine with guanine (C:G). The different ring structures of the purine and pyrimidine bases allow for this to occur through hydrogen bonds. Such base pairing maintains the geometry of the DNA structure and is the glue that holds the two strands together in their double helical form. The number of hydrogen bonds within these two sets of base pairs are different. A and T make two hydrogen bonds, while while C and G make three.
Base pairing other than that between A:T and C:G, known as mismatching, usually does not occur because such associations have little stability within the DNA structure. Spectroscopic studies performed in the 1960s showed that bases of the Watson-Crick base pair have a high mutual affinity because of their geometric and electronic complementarity arising from the atomic arrangements in the structures. Mismatches when they occur create distortions within the double helix which are rapidly located and repaired by proteins of the DNA repair machinery.
The base composition of DNA is governed by Chargaff's rules which, essentially, state that DNA has equal numbers of A and T residues and also equal numbers of G and C. These relationships were discovered in the 1940s by the Austrian born scientist, Erwin Chargaff, some time before base pairing within the DNA structure was fully understood. It is now clear that the basis for Chargaff's rules derives from the double stranded nature of the DNA and the specific pairing of the purine and pyrimidine bases. Consequently RNA, which usually occurs as a single-stranded molecule, has no such constraints on its base composition. The double-stranded RNA found in several viruses, however, does, obey Chargaff's rules as might be expected.
Chargaff additionally found that the base composition of DNA, expressed as (C+G)%, is constant within a species, but often differs widely between species. For example the C+G content in different species of bacteria can range from 25% to 75%. The C+G content appears to remain similar among related species and in mammals ranges from about 39% to 46%. The proportion of C+G can also give an indication of the thermal stability of a DNA molecule because C and G are held together by three hydrogen bonds while A and T are held together by only two. The more G and C residues a DNA molecule has, the more bonds have to be broken to melt the DNA, i.e., to separate the two strands. Thus the temperature required, the melting temperature, Tm, is higher for DNA with a high (C+G)%. This fact becomes important when applied to certain in vitro procedures which require controlled strand separation, such as the polymerase chain reaction (PCR).
It is interesting to speculate why the uracil (U) of RNA has been replaced by a thymine (T) in DNA. It would appear that T promotes an increase in stability against mutations and transcription fidelity, features which are critical for DNA. For example, the base cytosine (C) in DNA has a tendency to undergo a chemical reaction known as deamination, either spontaneously or by reaction with nitrites, and is converted to U. If U were a normal base in DNA, the deamination of cytosine would be highly mutagenic because there would be no indication of whether the resulting mismatched G:U base pair was originally a G:C or a G:U. Since T is the normal base in DNA instead of U, any U within the molecule is most probably a deaminated C. Thus Us detected in DNA are efficiently recognized and excised by the glycosylase of the base excision repair system (BER) and replaced by a C. Another reason for the presence of T rather than U in DNA is that it also improves the efficiency of DNA replication by reducing the rate of mismatches, and thus mutations, in the following way. T is effectively a methylated U. The addition of the hydrophobic (water hating) methyl (CH3) group to the fifth carbon position (C5) of U to give T changes the characteristics of the original U molecule. As most of the other components of DNA e.g. phosphates, sugars and the other bases, are hydrophilic (water loving), the methyl group is repelled by these other components and causes the T to move into a fixed position on the DNA. This solves an important problem with U because even though it pairs preferentially with A, it can also pair with reasonable affinity to almost any other base. The addition of the methyl group to U, making it T, stabilizes it to a single conformation and makes it more specific in pairing to A.
Some nucleic acids contain unusual or chemically modified bases. Unusual bases, other than the familiar A, T, G, C; and U, occur in tRNAs which carry the anticodon for the translation of the triplet base code to amino acids. tRNAs have a large proportion of such unusual bases which are thought to assist in the stabilization of the tRNA structure and assist in maintaining translation fidelity. The most common kind of chemical modification in nucleic acid bases is methylation. In DNA, for example, A and C bases may be methylated to form N°-methyladenine (m°A), N4-methycytosine (m4C) and 5-methylcytosine (m5C). The methyl groups project outwards and can interact with DNA binding proteins. In most cells only a few percent of susceptible bases are methylated, although in some plants more than 30% of the C residues have a methyl group. m5C is the only methylated base in vertebrates. In prokaryotes, such as the bacterium Escherichia coli, the A residues in all GATC sequences are methylated at the sixth nitrogen (N6) position. In this case the methyl group protects the DNA of E. coli from digestion by restriction enzymes occuring naturally within the organism, which attack and degrade unmethylated DNA. In eukaryotes, DNA methylation apparently controls gene expression. Variations in methylation are thought to be responsible for genomic imprinting in mammals, a phenomenon in which certain maternal and paternal genes are differentially expressed in the offspring.
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