Let’s talk about DNA. The genetic code is the blueprint used to build our bodies and that of every living being. At the very beginning of the 20th century, it was already known to scientist that the code was in genes, which in turn resided in chromosomes. In this series of articles I want to get through the incredible history and see how this most interesting of molecules works.

  • Discovering the Genetic Code: We today know that chromosomes are made of DNA, but how that became a known fact? We must begin by going back to the earlier part of the 20th century, to the work of an English physician named Frederick Griffith. This experiment that I am about to describe really provided the first insight into the chemical nature of genetic information.

  • Proteins Vs. DNA: In the early part of the 20th century, when Griffith published his work, there was generally an assumption that the genetic material must be a protein. Why did they think that? They thought it because pretty much everything that happens in the cell is done by a protein. It makes sense that if you got something complex and important that is being done in the cell, like providing information, it is probably going to be a protein.

  • The Code is in DNA: In the early 1950’s, Hershey and Chase took a novel approach in trying to found out what the genetic material might be made of, by looking at how a particular kind of virus worked.

How it Works

  • The Building Blocks: The building blocks of nucleic acids are called nucleotides. There are only four types of nucleotides. This is one of the reasons why nucleic acids seem relatively simple compared to proteins. Each nucleotide has a sugar that forms a ring.

  • The DNA Structure: 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.

  • Watson and Crick’s Double Helix: 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.

Understanding Replication

  • Theories of Replication: 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. 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. 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.

  • Watson and Crick had it right: Watson and Crick’s semi-conservative model contrasted with a couple of other possibilities for how DNA could possibly replicate. There is the conservative model, which suggests that both strands in the original DNA double helix stay together during replication. Then there is the dispersive model, which suggests that both strands are not only separated, but even broken up into smaller pieces during replication. Deciding which of these models was the correct one seemed to be pretty easy, because they make very different predictions. It was not obvious how to prove it in the laboratory, however.

  • The Process of Replication: In 1957, Arthur Kornberg made a really interesting discovery. He showed that DNA can be replicated outside of a cell, in a laboratory test tube. Kornberg wasn’t much interested in which model of replication was right. Instead, he was interested in specifically how replication occurred. Watson and Crick had suggested that the replication of DNA may not actually require an enzyme. If you could somehow unzip DNA, they thought that new DNA might just self-assemble, because the complimentary base-pairing would bring in all the appropriate nucleotides. Kornberg thought, though, that there must be some enzyme involved. He set out to figure out what that enzyme was.

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