6. What DNA Is (964)

At first glance, DNA doesn’t look like much--a long, repetitive chain of simple parts. And yet, this structure is capable of storing information and copying itself with extraordinary reliability.

Structure strongly shapes function--and DNA is one of the clearest examples of that principle in action.

When the structure of DNA was discerned by James Watson and Francis Crick (with key x-ray crystallographic data supplied by Rosalind Franklin), they understood immediately how it would function.

In their seminal 1953 article in the scientific journal Nature, they wrote--cheekily: "It has not escaped our notice that the specific (base) pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

The structure they proposed, which included base pairing, revealed how one of DNA’s primary functions--replication--could work.

Structure of DNA

At its core, DNA is a beautifully simple idea: a long string of letters, paired in a way that allows it to be copied.

Recall that DNA is a polymer--a chain of repeating subunits called monomers. The monomers of DNA are four different nucleotides. DNA being the double helix, it's really two polymers twisted around each other and weakly connected in the middle.

Let's untwist our double helix ladder so it looks like a real ladder with two side rails and rungs between them. Now let's cut the rungs down the middle so we're left with two separated DNA strands.

Zooming in on a nucleotide, it has three parts: a sugar, a phosphate, and one of the four different bases.

The sugar and phosphate parts of each nucleotide contribute to DNA's sugar-phosphate backbone--the rails of the ladder.

This backbone gives the molecule structure. It supports and positions the base so it can pair with its partner on the other strand. It is the bases that contain the genetic code.

Each full rung of the ladder is made of two bases sticking inward from the sugar-phosphate backbones of the two strands. These two bases are connected in the middle by relatively weak hydrogen bonds (and additional stabilizing interactions between stacked bases).

The two strands must be attached to each other or the double helix won't stay intact. But it's also important that the bonds be weak, because during both replication and transcription, the two strands must be separated.

Four bases

The four kinds of nucleotides are defined by their four different possible bases. We usually refer to nucleotides by the first letter of the name of their base: A (adenine), G (guanine), C (cytosine) and T (thymine).

The rungs of the ladder are composed of the bases of two complementary nucleotides. A is complementary to T and C is complementary to G. The bases of complementary nucleotides fit together nicely when paired. Non-complementary bases don’t fit properly or form stable pairs.

So based on their chemical shapes, a rung can consist of an A base extending inward from one of the rails and a T extending inward from the other the rail. Or a rung can consist of a G and a C. A rung cannot consist of a G and a T.

Also, it doesn't matter which of the two strands holds which base. A ladder rung can have an A base on one rail and a T to the other. Or it can have the A and the T on opposite rails. It only matters that A pairs with T.

The key point is simple: each base determines what must sit across from it. That simple pairing rule means that if the two strands are ever separated, each one contains the information needed to rebuild its partner.

With just four letters, DNA can encode every protein in your body.

A quick exercise

Try this before reading on.

Consider a small piece of DNA in which the order of the nucleotide bases is ACCTGTGCAA. This DNA strand is made of 10 nucleotides (a "10-mer") with the order of the nucleotide bases as shown.

The exercise: What would be the code on the opposite strand? (Hint: replace each base with its complementary partner)

If you said "TGGACACGTT" you'd be right.

If A pairs with T, then if we have an A as the first base on one strand, there must be a T across from it on the other.

Two important points

The first relates to the strength of pairing of complementary nucleotides. The A and T base are connected with two hydrogen bonds. But three hydrogen bonds form between G and C. It's easier to pull an A apart from a T than to pull a G apart from a C. This property of DNA will become relevant when we discuss replication.

The second concept--anti-parallelism--will also be important in replication.

The double helix may be like a twisted ladder, but it is a modified twisted ladder because the two rails run in opposite directions. It's as if we started with a perfect wooden ladder, sawed it down the middle, turned one of the rails upside down and then reconnected the rungs.

To distinguish the two orientations, scientists used the numbered carbons in the sugar ring (specifically the 5′ and 3′ positions where nucleotides link together).

One of the strands is called 5'-to-3' ("five prime to three prime") and the other 3'-to-5' ("three prime to five prime"). This is how we'll refer to the strands once we get into genome replication.

The fact that the rails are anti-parallel doesn't change the fact that the two strands of are complementary.

These details may seem small, but they matter. The strength of base pairing and the opposite orientation of the strands will shape how DNA is copied--and what challenges arise.

We now understand what DNA is. In the next chapter, we turn to what it contains--and how a simple sequence of nucleotides can be used to build proteins.