6.0 - Discovering the DNA Structure

Identifying the Genetic Material

To qualify as genetic material, a molecule must:

1. Store Information: It must contain instructions for the development, structure, and metabolic activities of the cell.

2. Be Stable and Replicable: It must be stable enough to be replicated accurately during cell division.

3. Undergo Changes: It must be capable of mutations to account for genetic diversity, especially in sexual reproduction.

Historical Discoveries

1869 - Discovery of Nucleic Acids

• Johannes Friedrich Miescher: A Swiss physician who isolated a substance he called "nuclein" from the nuclei of pus cells, which we now know as nucleic acids.

  • Types of Nucleic Acids:

    • DNA (Deoxyribonucleic Acid)

    • RNA (Ribonucleic Acid)

  • Significance: This discovery highlighted a dense region within the cell, suggesting a potential location for genetic material.

Nucleotides

• Components of Nuclein:

  • A sugar

  • A phosphate group

  • A nitrogenous base (Adenine, Guanine, Cytosine, Thymine)

• Early Understanding: While the structure was unknown, it was clear that these components were fundamental to nucleic acids.

The Big Question: Nucleic Acids or Proteins?

• Proteins: Contain 20 different amino acids that can be organized in numerous ways to determine traits.

• Nucleic Acids: Contain only 4 different nucleotides, raising questions about their capacity to store genetic information.

• Early Debate: In the early 1920s, scientists debated whether proteins or nucleic acids were responsible for heredity due to the complexity of proteins compared to nucleic acids.

Transformation of Bacteria

• Frederick Griffith’s Experiment:

  • Objective: To find a vaccine against pneumococcus bacteria.

  • Strains Used:

    • R Strain (Rough): Non-virulent

    • S Strain (Smooth): Virulent (infectious and harmful)

  • Griffith’s Transforming Principle: He discovered that when he mixed heat-killed virulent S strain bacteria with live non-virulent R strain bacteria, some factor transformed the R strain into a virulent form. This suggested the presence of a "transforming principle" that could transfer genetic information.

Griffith's Experiment with Bacterial Transformation

Background Information

• S Strain: Virulent because its polysaccharide coating prevents the immune system from attacking it.

• R Strain: Non-virulent, lacks the protective coating, and thus is not harmful.

Experimental Setup with Mice

Griffith used mice as a model organism to understand how bacteria can cause disease and to test his hypothesis about the transforming principle.

1. Infection with Live R Strain:

   • Result: The mice lived because the R strain is non-virulent.

2. Infection with Live S Strain:

   • Result: The mice died because the S strain is virulent.

3. Infection with Heat-Killed S Strain:

   • Result: The mice lived because the heat-killed S strain could no longer cause infection.

4. Combination of Heat-Killed S Strain and Live R Strain:

   • Result: The mice died. This surprising outcome suggested that some factor from the heat-killed S strain transformed the live R strain into a virulent form.

   • Observation: Griffith hypothesized that there must be some "transforming factor" that could transfer genetic information from the dead S strain to the live R strain, making it virulent.

5. Blood Transfusion Experiment:

   • Griffith took blood from the mice that died from the combination of heat-killed S strain and live R strain and injected it into other mice.

   • Result: The other mice also died, indicating that the transforming factor was present in the blood and could continue to cause transformation in new hosts.

Griffith's Experiment Recap

• Observation: Living R bacteria were transformed into deadly S bacteria by an unknown heritable substance, known as the "transforming factor."

• Question: Was this transforming factor nucleic acid or protein?

Key Points

• Griffith's Experiment: Suggested a transforming factor that could transfer genetic information.

• Avery, MacLeod, and McCarty's Experiment: Identified DNA as the transforming principle.

• Hershey and Chase Experiment: Confirmed that DNA is the genetic material by showing that DNA, not protein, enters bacterial cells during viral infection.

Key Discoveries Leading to the DNA Structure

Rosalind Franklin and Maurice Wilkins:

• X-ray Diffraction (Photo 51): Franklin and Wilkins used X-ray diffraction to take photographs of DNA, revealing its helical structure. Photo 51 was crucial in identifying the double helix form of DNA.

Watson and Crick

• Discovery Announcement: James Watson and Francis Crick used Chargaff’s ratios and Franklin’s X-ray images to build a model of DNA. They published their findings and made their announcement at the Cold Spring Harbor Laboratory, revealing the double-helix structure of DNA.