DNA and RNA structure

Three parts, one nucleotide

A nucleotide is three things joined together: a phosphate group, a pentose sugar with five carbons, and a nitrogen-containing base. The sugar sits in the middle, with the phosphate attached on one side and the base on the other. That arrangement is worth learning by position, because the phosphate and the sugar are what build the backbone while the base is the part that carries meaning.

Describe the drawing

A nucleotide drawn as three joined shapes: a circle for the phosphate group, a pentagon for the pentose sugar and a rectangle for the nitrogenous base. Below it, three nucleotides are joined into a strand in which phosphate and sugar alternate along the backbone, with the bases adenine, thymine and guanine hanging off the sugars and the two ends of the strand marked five prime and three prime.

The sugar differs between DNA and RNA. DNA contains deoxyribose, which is ribose with one oxygen fewer at carbon 2. The absence of that hydroxyl group makes DNA less reactive than RNA and therefore more stable over the lifetime of a cell.

Nucleotide

A phosphate group, a pentose sugar and a nitrogenous base joined together.

Polynucleotide

A chain of nucleotides joined by phosphodiester bonds between the sugar of one and the phosphate of the next.

Phosphodiester bond

The covalent bond joining the phosphate group of one nucleotide to the sugar of the next, formed by condensation.

Nucleotides join by condensation, as other biological monomers do. The phosphate of one nucleotide reacts with a hydroxyl group on the sugar of the next, water is released, and a covalent phosphodiester bond forms. Repeat that a few million times and you have a polynucleotide whose backbone is a strict alternation of sugar, phosphate, sugar, phosphate, with the bases projecting sideways. Hydrolysis reverses the reaction, which is how dietary DNA is digested before the nucleotides are absorbed.

Human chromosome 1 is a single DNA molecule roughly 249 million base pairs long. Stretched out it would be about 8 cm. Every phosphodiester bond along its backbone was made by the same condensation reaction.

The rungs: which base goes with which

Four bases appear in DNA: adenine, thymine, cytosine and guanine. They are not interchangeable. Adenine only ever pairs with thymine, and guanine only ever pairs with cytosine, and the reason is a matter of shape and of where the hydrogen-bond donors and acceptors sit on each ring system.

Adenine and guanine are purines, built from two fused rings. Thymine and cytosine are pyrimidines, built from one. So is uracil, the base RNA uses in thymine's place: the split into purines and pyrimidines covers all five bases, not just the four in DNA. Because every pair is a purine opposite a pyrimidine, every rung of the ladder is the same width, and the two backbones stay a constant distance apart all the way along. A purine facing a purine would bulge; two pyrimidines would pinch.

Purine

A base built from two fused rings: adenine and guanine.

Pyrimidine

A base built from a single ring: cytosine, thymine and, in RNA, uracil.

The hydrogen-bond counts are worth memorising as numbers rather than as an idea. A–T is two hydrogen bonds. G–C is three. Individually these are weak interactions, easily broken by an enzyme or by heat, which is what allows the strands to be separated whenever the sequence needs reading. Collectively, across millions of pairs, they hold the molecule together firmly.

Two strands, pointing opposite ways

The carbons in the pentose sugar are numbered 1 to 5, and the numbering is why the ends of a strand have names. At one end of a polynucleotide carbon 5 of the final sugar faces outwards, usually carrying a phosphate; that is the 5′ end. At the other, carbon 3 faces outwards, usually with a free hydroxyl group; that is the 3′ end. The names come from the carbon numbering rather than from whatever happens to be attached there, and a strand therefore has a direction, in the same way a sentence does.

Describe the drawing

A short stretch of double-stranded DNA drawn as a flat ladder. The upper strand reads A T G C A T from left to right with its five prime end on the left; the lower strand reads T A C G T A with its five prime end on the right. Between each pair of bases sit two short rungs for an A to T pair and three for a G to C pair, and an arrow beside each strand shows the two directions pointing opposite ways.

The two strands of a DNA molecule run in opposite directions. Wherever one strand has its 5′ end, the other has its 3′ end. That is what antiparallel means. DNA polymerase adds nucleotides in one direction only, so the two strands are not replicated in the same way, as the next lesson shows.

Wind the whole thing into a right-handed spiral and you have the double helix, with roughly ten base pairs per complete turn. The bases are on the inside, shielded from the water around them; the charged sugar-phosphate backbones are on the outside, where being charged lets them interact with water and, in eukaryotes, bind the positively charged histones.

Antiparallel

The two strands of a DNA molecule run in opposite directions: the 5′ end of one lies alongside the 3′ end of the other.

Complementary base pairing

Adenine pairs with thymine by two hydrogen bonds and guanine pairs with cytosine by three, so the sequence of one strand fixes the sequence of the other.

Double helix

Two antiparallel polynucleotide strands wound into a spiral, bases inside and backbones outside.

Relating DNA structure to its function

Link each structural feature to a specific requirement of the molecule. Four links cover most cases.

It is stable. The backbone is held by covalent phosphodiester bonds, the bases lie inside the helix away from water, and deoxyribose is less reactive than ribose, so the base sequence is preserved over long periods.

It is very long. There is no limit to how many nucleotides can be joined, so an enormous quantity of information fits into one molecule. The human genome runs to about 3.1 billion base pairs.

The base sequence carries the information. The backbone is identical everywhere and carries no information; the order of the four bases is free to vary and carries all of it. A stretch of only ten bases can be arranged in 4¹⁰ ways, a little over a million. Many scientists once doubted this. With only four kinds of nucleotide on a repeating backbone, DNA looked too simple to carry the genetic code, and proteins, built from twenty kinds of amino acid, seemed the likelier candidate until experiments in the 1940s and early 1950s showed that DNA is the genetic material.

The strands are complementary. Because the pairing rule is fixed, each strand is a full set of instructions for rebuilding the other. That is what makes accurate copying possible, and it is also why damage to one strand can often be repaired using the other as the reference.

One further feature applies where a question mentions packing: in eukaryotes the DNA is wound around histone proteins and coiled repeatedly, which is how 2 metres of DNA fits inside a nucleus about 6 μm across. In the bacteria this course describes, the DNA is circular, shorter and not wound around histones, though it is still supercoiled to fit. (The other prokaryote domain, the archaea, breaks the tidy rule: many archaeal species do carry histone proteins.)

RNA structure and the three kinds of RNA

RNA is a polynucleotide too, made the same way, with two changes. The sugar is ribose rather than deoxyribose, and uracil replaces thymine. Uracil pairs with adenine, using the same two hydrogen bonds thymine would have used, and since it is a single-ring pyrimidine like the thymine it stands in for, an A-U pair keeps the purine-against-pyrimidine geometry and the same width as every other pair.

DNA is a stable long-term store of sequence information; many RNA molecules are shorter-lived intermediates or functional products. The short lifetime of mRNA limits how long a protein continues to be synthesised after transcription of its gene stops.

Messenger RNA (mRNA)

A single-stranded copy of one gene, made in the nucleus and carrying codons to a ribosome in the cytoplasm.

Transfer RNA (tRNA)

A small folded RNA of about 80 nucleotides with an anticodon at one end and a binding site for a specific amino acid at the other.

Ribosomal RNA (rRNA)

RNA which, with proteins, forms the two subunits of a ribosome and catalyses the formation of peptide bonds.

Each of the three has a shape suited to what it does. mRNA is drawn as a straight run of codons because that is how the ribosome treats it; the real molecule folds back on itself in places and carries untranslated stretches at both ends, but its job needs no overall working shape, only a readable sequence. tRNA folds into a clover leaf held together by hydrogen bonds between complementary stretches of its own sequence, which puts the anticodon at one end and the amino acid at the other. rRNA does not carry a coding sequence; it is a structural and catalytic component of the ribosome.