DNA: Four Letters, One Molecule

An alphabet of four

DNA — deoxyribonucleic acid — is a chain built from four units called nucleotides. Each has three parts: a sugar (deoxyribose), a phosphate group, and one of four bases:

• A — adenine
• T — thymine
• C — cytosine
• G — guanine

The sugars and phosphates link into a backbone; the bases stick out sideways. That is the whole molecule: a monotonous rail with a sequence of four symbols attached to it. The information is entirely in the order of the bases, exactly as the information in this sentence is in the order of its letters and not in the ink.

The pairing rule

DNA is two such chains wound around each other — the double helix, worked out by Watson and Crick in 1953 using Rosalind Franklin’s X-ray diffraction images. The two strands are held together by hydrogen bonds between the bases, and here is the rule everything else depends on:

It is not arbitrary. A and G are large two-ring bases; T and C are small single-ring ones. A large must pair with a small or the ladder would bulge and pinch, and only these combinations put hydrogen-bond donors opposite acceptors. Chemistry allows exactly two pairings, and biology has used both ever since.

Two consequences follow immediately. First, the strands are complementary: given one, you can write the other with no extra information. That is what makes copying possible, and it is the subject of the next lesson. Second, C–G pairs have three hydrogen bonds to A–T’s two, so GC-rich DNA is harder to pull apart — which is why organisms living in hot springs tend to have GC-rich genomes.

Antiparallel, and why it matters later

The two strands run in opposite directions. Each has a 5′ end and a 3′ end (named for carbon positions on the sugar), and where one strand runs 5′→3′ the other runs 3′→5′. This sounds like bookkeeping until the next lesson, where it forces DNA replication into a distinctly awkward compromise.

Genes, chromosomes, genome

A gene is a stretch of DNA that specifies one product — usually one protein. A chromosome is one very long DNA molecule wound around packing proteins; you have 46, in 23 pairs. Your genome — the whole set — is about 3 billion base pairs, of which only around 1–2% actually codes for proteins. Much of the rest regulates when and where those genes are switched on, which turns out to matter enormously.