DNA: Structure and Copying

A typical human cell with a nucleus holds nearly 2 metres of DNA, packed into a nucleus only about 0.005 to 0.010 millimetres across. Before a typical cell divides, it copies roughly 6 billion base pairs of that DNA and gets almost every one right. Two metres is taller than most adults. How can a molecule that long fit in a space you cannot see without a microscope? And how can a cell copy it so accurately, again and again?

Explore: unzip and copy a DNA molecule

The simulation shows a short piece of DNA as two rows of labelled blocks, one block for each base. You unzip the two strands one step at a time and drop matching nucleotides into place on each open strand. A “mistake” button slips in a wrong base so you can watch what happens to it. At the end you see what has been built.

Try this.

1. Before you start, predict how many DNA molecules you will have at the end, and which strands each one will contain. Then copy the whole piece.
2. Pick one open strand and predict the base that must pair with each block before you drop it in. Test your predictions one at a time.
3. Press the mistake button. Predict whether the finished molecules will still match, then watch the mismatch and what the simulation does with it.
4. Compare the two finished molecules with the original. Predict which bases will differ, then check every pair.

Explain: a twisted ladder of four bases

DNA is a polymer, a long chain built from small repeating units. Each unit is a nucleotide, a building block made of three parts: a sugar called deoxyribose, a phosphate group and a base. A base is the part of a nucleotide that carries information, and DNA uses four of them: adenine (A), thymine (T), cytosine (C) and guanine (G). Nucleotides are named by their base, so you will hear about “an A” or “a G.”

Along one strand, the sugar of one nucleotide is joined to the phosphate of the next by a covalent bond, a strong bond in which atoms share electrons. That makes a sugar-phosphate backbone with the bases sticking out to one side.

Two strands line up with their bases facing each other in the middle. A hydrogen bond is a weak attraction between molecules or parts of molecules, and hydrogen bonds hold each pair of facing bases together. The two strands then twist around each other into a double helix, a shape like a ladder twisted along its length. The backbones are the sides of the ladder, and the base pairs are the rungs.

Base pairing is the rule that A always pairs with T and C always pairs with G across the two strands. Picture a zipper whose teeth only close with the right partner. The analogy breaks because a zipper’s teeth carry no message, while the order of DNA’s bases does.

The two strands also run in opposite directions, like two lanes of a road. Each strand has a distinct “head” end and “tail” end, and the strands lie head to tail.

The order of the bases is the information. A gene is a region of DNA whose base order, in most genes, codes for a protein; a few genes code for RNA molecules that do jobs of their own. A chromosome is one very long DNA molecule wrapped around proteins, and it carries many genes. Only about 1 to 2 percent of human DNA codes for proteins. Other stretches control genes, help hold chromosomes in shape, or have jobs nobody has found yet. The genetic code that turns base order into protein is almost the same in every living thing, which is why bacteria can be engineered to make some human proteins, such as insulin. From DNA to protein shows how that code is read.

Every cell that grows and divides carries DNA. In plants, animals and fungi most of it sits inside the nucleus, with small extra pieces in organelles such as mitochondria. Bacteria keep their DNA in a nucleoid, a region of the cell with no membrane around it.

Explain: copying DNA one strand at a time

Replication is the copying of a DNA molecule before a cell divides. Because A must pair with T and C with G, each strand carries everything needed to rebuild its partner. Each old strand works as a template, a pattern that sets the order of the new strand.

Copying is done by enzymes. An enzyme is a protein that speeds up a chemical reaction without being used up. The steps, in order:

1. An enzyme unwinds the helix and unzips it, breaking the hydrogen bonds between the base pairs. The covalent backbones stay whole.
2. Free nucleotides float nearby in the cell. Each one pairs with its matching base on an open strand: A with T, C with G.
3. Another enzyme, DNA polymerase, joins the new nucleotides into a strand with covalent bonds.
4. The result is two DNA molecules. Each has one old strand and one new strand, and both have the same base order as the original.

Why only one direction? DNA polymerase can attach a new nucleotide only to one particular end of a growing strand, the tail end. So every new strand grows the same way, adding at its tail. The two templates point in opposite directions. One new strand can grow smoothly toward the unzipping point. The other grows away from the unzipping point, so it must be built in short pieces, each started fresh as more template opens up. Another enzyme then joins the pieces.

How close to “almost perfect” is it? DNA polymerase checks each new base and removes most wrong ones, a step called proofreading. Repair enzymes catch many errors that slip past. A textbook estimate is about one uncorrected mistake for every billion bases copied. Across roughly 6 billion base pairs, that leaves roughly a handful to a dozen changes per copy. Those rare changes are mutations, and mutations can change proteins.

Elaborate: do the bases really pair up?

If A always pairs with T, a sample of double-stranded DNA should hold as much A as T, and as much G as C. Here is base-composition data in the style of Erwin Chargaff’s measurements from around 1950.

Source: a representative sample of Chargaff’s 1952 data as reprinted in a review (Bansal, Current Science 85:1556-1563, 2003, Table 1) and in the Wikipedia table “Chargaff’s rules” that cites it. We could not open Chargaff’s original papers, so treat each row as an example. Rows are measured averages, so some do not add to exactly 100.

1. In each row, how far apart are A and T? How far apart are G and C? Which row has the biggest gap?
2. Add A and T for the E. coli row and for the sea urchin row. How different are they?
3. Does any organism have all four bases at 25 percent?

Design problem

Every cell in an animal’s body grows from one fertilized egg by copying DNA. Plan an investigation to test whether DNA from different tissues of one animal has the same base composition, and whether it differs from another species.

Evaluate: check your thinking

The 2 metres of DNA fit because the molecule is extremely thin and is wound tightly around proteins. The near-perfect copying comes from the structure itself. Each strand is a template for the other, base pairing allows only one correct partner at each spot, and proofreading removes most of the rare mistakes.

Science practices you used: making predictions and testing them with a model, naming where a model or analogy breaks, reading a data table and comparing values, making a claim from evidence with reasoning, and planning an investigation with controls and repeated trials.