DNA Structure and the Historical Discovery of Genetic Material

This specific bonding pattern gives the DNA strand polarity, meaning it has a distinct direction. One end of a strand is the $5'$ end (terminating in a phosphate), and the other is the $3'$ end (terminating in a hydroxyl group). Because of this, DNA is described as having an "antiparallel" structure, where the two strands run in opposite directions.

Study Tip: When identifying the direction of a DNA strand, always look for the phosphate group. The end with the phosphate is the $5'$ end, and the end with the free $-OH$ group is the $3'$ end.

The Historical Experiments: Identifying the Genetic Material

The journey to identifying DNA as the genetic material involved three pivotal stages of research, moving from observing "transformation" to identifying the specific molecule responsible.

1. Griffith’s Experiment: The Discovery of Transformation

In 1928, Frederick Griffith worked with Streptococcus pneumoniae, a bacterium that causes pneumonia. He utilized two different strains:

• Smooth (S) strain: Virulent (deadly) because it produces a polysaccharide coat that hides it from the host's immune system.
• Rough (R) strain: Non-virulent because it lacks the enzyme to make that protective coat.

Griffith observed that when he injected mice with a mixture of heat-killed S-strain bacteria and living R-strain bacteria, the mice died. He concluded that a "transforming principle" had passed from the dead S-strain to the living R-strain, changing the R-strain into the virulent S-strain.

2. Avery, MacLeod, and McCarty: Identifying the Molecule

While Griffith discovered that transformation happened, he didn't know what caused it. In 1944, Avery, MacLeod, and McCarty sought to identify the substance. They systematically destroyed different components of the bacteria:

• When they destroyed proteins or RNA, transformation still occurred.
• When they destroyed DNA (using DNase), transformation stopped.

This provided strong evidence that DNA was the "transforming principle". However, many scientists remained skeptical, arguing that the results might be due to protein contaminants.

3. The Hershey-Chase Experiment: The Final Proof

In 1952, Alfred Hershey and Martha Chase used bacteriophages (viruses that infect bacteria) to settle the debate once and for all. Bacteriophages are ideal for this because they have a very simple structure: a protein coat and a DNA core.

By labeling the viral protein with one radioactive marker and the viral DNA with another, they could track which substance actually entered the bacterial cells during infection. Their results showed that only the DNA entered the bacteria to direct the production of new viruses, proving that DNA is indeed the genetic material.

Summary of Key Findings

Exam Reminder: Be prepared to distinguish between the different types of bacterial transfer and the specific roles played by the S and R strains in Griffith's work.