The DNA Structure, Part II

James Watson was a young American, who had just completed his PhD. He was interested in protein structure. He moved to Cambridge, England, and began working with Francis Crick, who was a physicist familiar with x-ray crystallography and how to interpret it. The story goes that Watson happened to visit London for a seminar, and saw the x-ray diffraction patterns that Rosalind Franklin had obtained from Maurice Wilkins’ purified DNA. Watson made some notes, rushed back to Cambridge and told Crick what he had seen.

Using Franklin’s data, Watson and Crick were able to deduce a number of key structural elements about how DNA must be shaped. These are things they figured out by looking at those dots on the x-ray crystallograph. First, they learned that the molecule had to form some kind of helix. It had to have a kind of spiral structure, similar to the alpha helix that is characteristic of many parts of proteins. Second, they figured out that the width of this helix was about two nanometers. The interesting thing about this is that, this width was twice the width of what you would have expected if there was only a single helix. That gave them the idea that there had to be more than one helix. A double helix, perhaps.

Another thing they learned was what the regular spacing of the repeated patterning along the length of the molecule is. They saw that there was a repeating pattern at about 0.3 nanometers. This corresponded to the size of one nucleotide. Then there was a larger repeating pattern that was ten times that size. From this they inferred that the number of nucleotides that would occur when the spiral went around just once and returned to the same point in the spiral had to be about ten nucleotides.

That isn’t a lot of information. If I gave you that information you couldn’t tell me the structure of DNA. What Watson and Crick did was to use that data and set out to figure out the structure of DNA the old-fashioned way. They made physical models of the molecule with metal rods. They made large-scale models of DNA several feet tall.

They built many models and asked each time: when we have this model, does it all fit together? They tried over and over again. Eventually they came up with a model that fit. The trickiest part of the modeling was to figure out how the nitrogenous bases fit into the picture. Remember, a polymer of DNA is a repeating pattern of sugars and phosphates, with different nitrogenous bases hanging off the side (the guanines, the adenines and so forth). Where did they fit? If you had two, or even more molecules of DNA that were spiraling together, where do the nitrogenous bases go?

Well, after a couple of failed attempts putting the nitrogenous bases on the outside, Watson and Crick realized they had to go on the inside. Why they might want to put them on the outside? It is the nitrogenous bases that vary along the length of the molecule. It is the variation of the different kinds of nucleotides that must somehow involve the code. If we’re going to get access to that code, we’ve got to make what’s different about that code available to the outside world. They couldn’t get the backbones to work together in any way that made sense with the nitrogenous bases on the outside.

If they turned those nitrogenous bases in, and had the nitrogenous bases connecting with each other, forming kind of stairs, with the backbones of these molecules forming the stringers that are holding the steps; the molecule began to fit together. This actually made sense, because these nitrogenous bases are chemical repelled by water. They want to be on the inside of the molecule because of that.

There was one interesting additional problem. This is actually the most interesting part of the story. That is, how did the bases fit together? If the put the nitrogenous bases on the inside, they could get a double helical structure that began to fit the data, but there was still a problem remaining, there are two kinds of bases, the pyrimidines and the purines, and they are of different sizes. Purines have two rings, and pyrimidines only have one.

If you just try to put these stair steps across the two sides of the double helix, you’ll have some steps that are wider, and some that are narrower. For example, if you got two purines together, you’ll have a relatively narrow step. The outside of this spiral would be going in and out, which is not structurally stable. That’s were Chargaff's rule came in. They realized the implications of Chargaff's rule, which says that the amount of the base adenine (A), always equals the amount of thymine (T). Similarly, the amount of guanine (G), always equals the amount of cytosine (C). This suggested that it may be that one always pairs up with the other when they are matching together on the inside of the helix.

It turns out that when they looked at how these kinds of nitrogenous bases would match up, they found that those peculiar combinations (A and T, C and G) would always maximize that potential weak bonding that occurs between the bases. With this, they actually solved two problems. They figured out how you can have a regular distance along the whole length of the staircase. Also, they figured out what could hold the staircase together. If you always match A with T and G with C, the bonding that holds two sides together is maximized.

In April, 1953, which is only a year after people became convinced that DNA was the information molecule, Watson and Crick published a one-page paper in the journal Nature, which described the double helix. They described the molecular structure and how they thought it would all fit together. The real significance of this work was not simply to describe the 3D structure of DNA, but to show how that 3D structure might actually say something about replication.

Watson and Crick’s paper ends with the following sentence: “It had not escaped our attention that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

The fact that A and T, G and C were always paired together, meant that if you took the two sides of the molecule apart, you would always know what the other side has to be. That’s called complementary base-pairing. It was this fact that suggested that mechanism by which DNA was replicated. I’m very excited about this subject, but I will leave it to another article.

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