8.1 Watson-Crick Model

8.1 Watson-Crick Model

The double helix is the 1953 model of DNA. Two strands coil around a shared axis. Each strand is a polymer of nucleotides, and each nucleotide has three parts: the sugar deoxyribose, a phosphate group, and one nitrogenous base. The sequence of bases is the stored information. The shape of the molecule shows how the two strands stay paired, how the sequence of one strand specifies the sequence of the other, and why some stretches of DNA come apart more readily than others. This section is the model itself. The enzymes that open a replication fork and build new strands belong to the next section.

Strands That Run in Opposite Directions

The two strands are antiparallel. Their chemical directions are opposite. Follow one strand from its 5-prime end to its 3-prime end, and the partner beside it runs from 3-prime toward 5-prime. The 5-prime end carries a phosphate attached to carbon 5 of deoxyribose. The 3-prime end has a free hydroxyl group on carbon 3 of the sugar. Those ends tell a later enzyme which way a strand can be read and which way a new chain can grow. A drawing that sends both strands from 5-prime to 3-prime in the same direction does not match the Watson-Crick model. Each end of the helix has one 5-prime end beside one 3-prime end.

The Backbone Outside and the Bases Inside

The sugar-phosphate backbone lies on the outside of the helix. Sugars and phosphates alternate along each strand. A phosphodiester linkage joins the 3-prime carbon of one sugar to the phosphate on the 5-prime carbon of the next nucleotide. Those covalent bonds hold a single strand together. They stay intact when the two strands separate. The bases project inward and stack on one another near the center, away from the surrounding water. A twisted ladder is a fair picture: the backbone is each side rail, and the paired bases are the rungs. The rails are the strong covalent chain. The contacts between rungs are weaker and can be opened when proteins need to read the sequence, without chopping the strand into free nucleotides.

Complementary Pairing and Hydrogen Bonds

Complementary base pairing is specific. Adenine pairs with thymine. Guanine pairs with cytosine. Adenine does not pair with guanine, and thymine does not pair with cytosine. Adenine and guanine are purines, the larger bases, each built from two rings. Thymine and cytosine are pyrimidines, the smaller bases, each built from one ring. A purine always meets a pyrimidine, so each rung has about the same width. Two purines would make the rung too wide. Two pyrimidines would make it too narrow. That geometry is one reason the pairing rules are strict.

Hydrogen bonds hold each pair together, and the two kinds of pairs are not equal. Adenine and thymine share two hydrogen bonds. Guanine and cytosine share three. A stretch rich in guanine and cytosine is harder to separate than a stretch rich in adenine and thymine, because more hydrogen bonds must be broken. The covalent backbone remains a continuous chain when those hydrogen bonds are broken. Ordinary strand separation does not cut the DNA into free nucleotides.

Chargaff's rule describes double-stranded DNA. The amount of adenine equals the amount of thymine, and the amount of guanine equals the amount of cytosine. The equalities are a consequence of pairing. If adenine is 22 percent of the bases in a double helix, thymine is also 22 percent, and the remaining 56 percent is split equally into 28 percent guanine and 28 percent cytosine. A single strand does not have to satisfy the rule, because it has no partner yet. Once that strand is paired, every adenine demands a thymine and every guanine demands a cytosine, so the equalities show up in the duplex.

A Four-Base Complement You Can Check

Direction is part of the sequence. One strand written 5'-ATGC-3' has the partner bases thymine, adenine, cytosine, and guanine, but the partner strand points the other way. Beside the first strand, the complement is 3'-TACG-5'. Turn that same partner so its 5-prime end is on the left and it reads 5'-GCAT-3'. Both writings name one strand. Copying the bases in order without reversing the direction loses the complement.

Check the pairs one base at a time. Adenine meets thymine, thymine meets adenine, guanine meets cytosine, and cytosine meets guanine. This short duplex also matches Chargaff's rule: one adenine with one thymine, and one guanine with one cytosine. The partner is not a second copy of 5'-ATGC-3'. It is not a same-direction strand that puts adenine opposite guanine. Opposite direction, adenine with thymine, and guanine with cytosine are the model.

Grooves, the Helix, and the Structural Evidence

In the common B form of DNA, about ten base pairs make one full turn. The flat bases stack inside the coil. The way each base pair sits relative to the two backbones leaves a wider major groove and a narrower minor groove. Proteins that recognize a particular sequence can often contact the edges of the bases from a groove without taking the two strands fully apart. That contact is a fact about the finished double helix.

Rosalind Franklin's X-ray diffraction patterns of DNA fibers supported a helix with the bases stacked toward the interior. The photographs were evidence about shape. The Watson-Crick model joins that helical pattern to the outside backbone, the inside bases, the opposite strand directions, and the pairing rules. On a diagram, confirm opposite strand directions, adenine opposite thymine, guanine opposite cytosine, and three hydrogen bonds in each guanine-cytosine pair.