What type of organic molecule is this?

Here’s a hint: molecules like this one determine many physical features about you. They contain genetic information that controls your physical characteristics. They determine your eye color, facial features, and other physical attributes. What molecule is it?

You probably answered "DNA." Today, it is commonly known that DNA is the genetic material. For a long time, scientists knew such molecules existed. They were aware that genetic information was contained within organic molecules. However, they didn’t know which type of molecules play this role. In fact, for many decades, scientists thought that proteins were the molecules that carry genetic information.

DNA, the Genetic Material

DNA, deoxyribonucleic acid, is the genetic material in your cells. It was passed on to you from your parents and determines your characteristics. The discovery that DNA is the genetic material was another important milestone in molecular biology.

Griffith Searches for the Genetic Material

Many scientists contributed to the identification of DNA as the genetic material. In the 1920s, Frederick Griffith made an important discovery. He was studying two different strains of Streptococcus bacteria, called R (rough) strain and S (smooth) strain. He injected the two strains into mice. The S-strain was virulent and killed the mice, but the R-strain was non-virulent and would not kill the mice. Griffith also injected mice with S-strain bacteria that had been killed by heat. As expected, the heat destroyed bacteria did not harm the mice. However, when the dead S-strain bacteria were mixed with live R-strain (non-virulent) bacteria and injected, the mice died.

Based on his observations, Griffith deduced that something in the heat-destroyed S-strain was transferred to the previously harmless R-strain, transforming the R-strain into virulent form of Streptococcus bacteria. He called this process transformation, as something was "transforming" the bacteria from one strain into another strain. What was that something that transformed the non-virulent bacteria into a virulent form? What type of substance could change the characteristics of the organism that received it?

Avery, MacLeod, and McCarty Make a Major Contribution

In the early 1940s, a team of scientists led by Oswald Avery tried to answer the question raised by Griffith’s results. Avery, together with his colleagues Colin MacLeod and Maclyn McCarty, inactivated various substances in the heat-destroyed S-strain Streptococcus bacteria. They then mixed the heat-destroyed S-strain bacteria with the harmless R-strain bacteria. When proteins and RNA were inactivated, the R-strain still transformed into the deadly S-strain. This ruled out proteins and RNA as the genetic material. Why? Even without the S-strain proteins or RNA, the R-strain was changed or transformed, into the deadly S-strain. However, when the researchers inactivated DNA in the S-strain, the R-strain did not transform. This led to the conclusion that DNA is the substance that controls the characteristics of organisms. In other words, DNA is the genetic material.

Hershey and Chase Seal the Deal

The conclusion that DNA is the genetic material was not widely accepted at first. It had to be confirmed with more research. In the 1950s, Alfred Hershey and Martha Chase did experiments with viruses known as bacteriophages, a virus that infects bacteria, and bacteria.

Viruses are not made of cells. Bacteriophages are basically DNA inside a protein coat. To reproduce, a virus must insert its own genetic material into a cell (such as a bacterium). Then it uses the cell’s machinery to make more viruses. The researchers used different radioactive elements to label the DNA and proteins in viruses. The protein was labeled with radioactive sulfur (³⁵S), while the DNA was tagged with radioactive phosphorus (³²P) This allowed them to identify which molecule the viruses inserted into bacteria.

When they examined the bacteria that the radioactive-labeled viruses were using to replicate themselves, they failed to discover any ³⁵S but ³²P was discovered. Recall that the viral DNA was tagged with ³²P at the beginning of their experiment. This meant that DNA was confirmed to be the genetic material.

Timeline of the Discovery of DNA

Shown in the figure below is a timeline of the work of several researchers that led to the establishment of DNA as the genetic material followed by the discovery of its structure.

Have you ever seen a ladder? Imagine being able to twist the ladder. The basic shape of DNA is sometimes described as a twisted ladder. Do you see the resemblance? Which parts of the DNA molecule are like the steps of the ladder? What about the railings? There are other ways you can represent or model the structure of DNA in order to better understand its function. The discovery of DNA’s structure actually involved modeling. A model is a very useful tool in science. Models provide a way to explore things that might be too complex or small to investigate directly. So how might you create a model of DNA?

DNA Structure

Chargaff's Rules

Other important discoveries about DNA were made in the mid-1900s by Erwin Chargaff. He studied DNA from many different species. He was especially interested in the four different nitrogenous bases of DNA: adenine (A), guanine (G), cytosine (C), and thymine (T).

Chargaff found that concentrations of the four bases differed from one species to another. However, within each species, the concentration of adenine was always about the same as the concentration of thymine. The same was true of the concentrations of guanine and cytosine. These observations came to be known as Chargaff’s rules. The significance of the rules would not be revealed until the structure of DNA was discovered.

The Double Helix

After DNA was found to be the genetic material, scientists wanted to learn more about it. James Watson and Francis Crick are usually given credit for discovering that DNA has a double helix shape, like a twisted ladder.

The discovery was based on the prior work of Rosalind Franklin and other scientists, who had used X-rays to learn more about DNA’s structure. Franklin and these other scientists have not always been given credit for their contributions. With the help of prior work from other scientists, Watson and Crick developed a model of the DNA double helix structure that correctly matched what was observed in Franklin’s X-ray crystallography photos.

The double helix shape of DNA, together with Chargaff’s rules, led to a better understanding of DNA. DNA, as a nucleic acid, is made from nucleotide monomers, and the DNA double helix consists of two polynucleotide chains. Each nucleotide consists of a sugar (deoxyribose), a phosphate group, and a nitrogenous base (A, C, G, or T).

Complementarity of Nitrogenous Base Pairs

Scientists concluded that bonds (hydrogen bonds) between complementary bases hold together the two polynucleotide chains of DNA. Adenine always bonds with its complementary base, thymine. Cytosine always bonds with its complementary base, guanine. If you look at the nitrogen bases in the figure above, you will see why. Adenine and guanine have a two-ring structure. Cytosine and thymine have just one ring. If adenine were to bind with guanine and cytosine with thymine, the distance between the two DNA chains would be variable. However, when a one-ring molecule binds with a two-ring molecule, the distance between the two chains is kept constant. This maintains the uniform shape of the DNA double helix. These base pairs (A-T or G-C) stick into the middle of the double helix, forming, in essence, the steps of the twisted ladder.

DNA Replication

DNA replication begins when an enzyme, DNA helicase, breaks the bonds between complementary bases in DNA. This exposes the bases inside the molecule so they can be “read” by another enzyme, DNA polymerase, and used to build two new DNA strands with complementary bases also DNA polymerase. The two daughter molecules that result each contain one strand from the parent molecule and one new complementary strand. As a result, the two daughter molecules are identical to the parent molecule. DNA polymerase has the remarkable ability to proofread and correct its own mistakes. If it incorporates the wrong base at any point, it corrects itself immediately and only then proceeds with the replication process.

DNA replication is a semi-conservative process because half of the parent DNA molecule is conserved in each of the two daughter DNA molecules.