DNA Replication, Part I

Lately I’ve been writing a lot about DNA, its history and structure. I think this is really important, I would say key, to understanding what is life about, and how it evolves. Here I’ll continue with this business. Here I want to look at the proposal Watson and Crick had for how the double helix might be replicated because of the complimentary base-pairing they discovered. This would be a series on DNA replication, which I think is one of the most fascinating and complex processes in the universe.

Watson and Crick suggested that the DNA molecule must unzip, and then, each half of the molecule could serve as a template for a newly formed half. This is a good hypothesis, but was it correct? As Watson and Crick proposed that, there were two alternative hypotheses on the scene.

The Alternative Hypotheses

The first alternative suggested that the DNA double helix must remain completely intact when it is replicated. That is, the two strands do not separate. The entire molecule is somehow used as a template for making more DNA. This alternative was called the conservative hypothesis of replication. The original DNA double helix molecule remained completely intact and conserved. The idea was that there must be some intermediate molecule that got information from the structure of the helix and used it to build a completely different helix.

A second alternative suggested that the original DNA molecule becomes completely broken down during replication, with the newly copied DNA assembled by some unknown mechanism. In other words, the DNA double helix would actually be irrelevant. This alternative was called the dispersive model. It was called dispersive obviously because the DNA in the original helix just becomes dispersed and incorporated in the new copies that were being created.

Based on what was known about molecular biology and DNA in the 1950’s, both of these hypotheses were reasonable. Neither offered a solution to the problem of duplicating the exact order of nucleotides, however. This order is the information that we are seeking. Based on what we know today, both of these alternatives seem unlikely. They’re value then was to serve as alternative hypotheses against which to test specific predictions made by the Watson and Crick model.

The mechanism that Watson and Crick proposed became known as the semi-conservative model of DNA replication. This was called semi-conservative because it predicts that during replication, the double helix unzips and the new daughter helixes would both have one strand of the old helix. We begin with one helix, it separates somehow, and the resulting daughter helixes that are formed maintain the original halves of that parent helix. Upon this old half, new halves are formed to create the new double helixes.

This hypothesis led to a specific prediction. The prediction was that if you could know which was old and new DNA after replication would occur, all the old DNA that was in the original parental double helix, would now be dispersed between the two daughter helixes equally. The daughter helixes would all be composed of one half of old DNA, and one half of new DNA.

Let’s contrast that to the prediction we might have if we look at the other two models. Let’s think about the conservative model first. That model suggests that the DNA helix just remains intact once you’ve got it. After replication, that model would suggest that the two daughter helixes would separately made up of, on the one hand all old DNA, and on the other hand, all new DNA. The old DNA in the original parent is still in the original parent, and the daughter DNA helix is completely new.

The dispersive model made yet another prediction. That prediction was that the old DNA that was found in the original parental helix would just randomly scattered across the two daughter helixes.

We have three specific and different predictions that could be used to distinguish between these three models of replication. The trick is figuring out how to know what’s old and new DNA. Actually, it was several years after Watson and Crick’s original proposal that anybody could figure out how to experimentally test it.

The way to test the hypothesis was pretty obvious conceptually. Let’s ask ourselves, after replication, what happens to the material in the original parent’s helix? We have very distinct predictions. The problem was figuring out how to know where old and new DNA was. This is often it is in science. An idea comes forward, people understand what they have to do, but the critical experiment isn’t actually done until somebody comes along and says not what’s the experiment, but how you can actually do it. This may take years, as it did in this case.

Eventually, researchers figured out an extremely clever way to know what the difference is between old and new DNA. I will talk about this interesting and brilliant experiment in my next article.

1 Comment:

mapillay said...

so how do you tell the diff between a DNA taken last year and taken today?????


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