The DNA Structure, Part I

After the work of Hershey and Chase, biologists in the early 1950’s became convinced that DNA was what they needed to look at to understand the genetic code. They actually had no idea how DNA could possibly act as a mechanism for genetic inheritance. Let’s step back and remind ourselves of what this molecule has to accomplish. It needs to do two things. First, it needs to have some way of providing a code that can store information about proteins.

The linear structure of DNA, with variable bases along the chain was consistent with the idea that could provide such a code. Proteins also are linear chains. So, you can imagine that there could be some sort of mapping of the pattern of one molecule in the pattern of the other. It wasn’t clear what this mapping could be, but they thought they could figure that out. I will talk about that code in another article.

Second, the molecule had to be able to replicate. If we are going to transmit genetic information, from one generation to the next, it won’t work unless we make duplicate copies of the code, so we can handle one copy of the blueprint to the offspring. The real problem was that it wasn’t clear how DNA could be replicated. The linear structure of DNA offer some hope for a code, but it didn’t offer a clue about how replication might occur.

This is where the race, literally a race, for discovering the three-dimensional structure of DNA began. Scientists were convinced they needed to know the three dimensional structure of DNA to understand replication. It was this impetus that led to the discovery of the now famous DNA double-helix, by Watson and Crick. This was arguably the most important finding in biology in the 20th century.

Why biologists should be interested in the three-dimensional structure of DNA? Biochemists had begun to understand, in the 1950’s, that the function of proteins could be understood by figuring out something about their structure. So, it was hoped that some aspect of the function of DNA, specifically how it was replicated, could be understood by deducing its structure.

What kind of evidence could you use to deduce the three-dimensional structure? The first kind of evidence came from a procedure known as x-ray crystallography. The positions of atoms in a crystal can be inferred from the pattern that they create when you shoot a beam of x-rays through that substance. The x-rays would bend around those atoms, and then, when you look at the pattern on the other side, you see lines and dots in particular orientations and spacing. From them, if you’re familiar with the procedure and very clever, you’ll able to deduce something about the relative positions and orientations of the atoms that make up that structure.

If you shoot an x-ray through a relatively simple crystal, you’ll get a very regular pattern. If you shoot an x-ray through a more complex material, like an organic molecule, you’ll get a much more complex pattern. It is pretty difficult to pull information form that pattern, and infer something about the way the molecule must be structured.

You may be asking, what are we talking about here, crystals or organic molecules? Well, even the most complex organic molecules, in the hands of a good biochemist, can be crystallized. In fact, that’s where the story starts. Maurice Wilkins, a biochemist working at King’s College in London, was able to produce a remarkably pure crystal of DNA. Working with Wilkins was a woman named Rosalind Franklin. She was an expert x-ray crystallographer. She took Wilkins’ purified DNA crystal and was able to get what was to that point the most clear and accurate x-ray crystallograph of DNA that had yet been obtained.

As I said, these patterns are quite hard to interpret. Nowadays we can use computers and algorithms to deduce the structure of proteins from this kind of data, but back then was pretty much painstaking hand calculation and educated guesswork. As it turns out, Wilkins and Franklin puzzled over their x-ray crystallograph trying to deduce something about the structure of DNA. They didn’t quite figure it out. By the time, another person arrived on the scene, James Watson.

Before I introduce Watson, I want to introduce another kind of clue. There was a scientist working at Columbia University named Erwin Chargaff, who discovered a peculiar thing about DNA. He found that if you took the DNA from any organism, and decomposed it into its component nucleotides, you always found a quite interesting relationship. You always found 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). So, if you take apart the DNA of any organism, you always will find that the amount of A equals the amount T, and the amount of G equals the amount of C.

This was a very curious relationship that became known as Chargaff’s rule. Next time we’re going to talk about James Watson and his codiscovery of the double-helix with Francis Crick.

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