Dna Structure Griffith Experiment

6.1 The Search for the Genetic Material

By the early 1900s, scientists knew that genes existed on chromosomes — but chromosomes contain BOTH protein and DNA. Which is the actual genetic material? For decades, most scientists believed proteins (with their 20 amino acids) were "complex enough" to carry hereditary information; DNA (with only 4 nucleotides) seemed too simple.

6.1.1 Griffith's Transforming Principle (1928)

Frederick Griffith worked with two strains of Streptococcus pneumoniae:

• S strain (Smooth) — has polysaccharide capsule, virulent (causes pneumonia, kills mice).
• R strain (Rough) — no capsule, non-virulent (mice live).

Griffith conducted four experiments:

The shocking result: dead bacteria + harmless live bacteria → killer bacteria. Griffith concluded that some chemical substance in the dead S strain "transformed" the live R strain into virulent S strain. He called this the transforming principle. He didn't know what the chemical was.

6.1.2 Avery, MacLeod & McCarty (1933–44)

Sixteen years later, three scientists at Rockefeller University set out to identify Griffith's mysterious transforming principle. Their approach: take heat-killed S strain extract and selectively destroy each component (proteins, RNA, DNA) using specific enzymes:

• Add protease (digests proteins) → R still transformed to S. So protein is NOT the transforming principle.
• Add RNase (digests RNA) → R still transformed to S. So RNA is NOT it.
• Add DNase (digests DNA) → transformation STOPPED. No more S strain produced!

Conclusion: DNA was the transforming principle — the genetic material that converted R into S. Despite this elegant proof, many biologists still resisted, citing DNA's "simplicity."

6.1.3 Hershey-Chase Experiment (1952)

Alfred Hershey and Martha Chase used bacteriophage T2 — a virus made only of protein and DNA. Their goal: which one enters the bacterium during infection and directs the production of new viruses?

They used radioactive labelling:

• Batch A: Phages grown with radioactive sulfur (³⁵S). Only proteins (which contain S) become radioactive.
• Batch B: Phages grown with radioactive phosphorus (³²P). Only DNA (which contains P) becomes radioactive.
• They infected E. coli with each batch separately, then sheared off the phage coats with a blender and centrifuged.

Conclusion: Only DNA enters the bacterium during infection — DNA must be the genetic material. This experiment, combined with Avery's findings, finally convinced biologists that DNA is the genetic material.

6.2 Structure of DNA — The Watson-Crick Double Helix (1953)

In 1953, James Watson and Francis Crick published their model of DNA structure in the journal Nature. They built on:

• Erwin Chargaff's rules: In any DNA, A=T and G=C (and total purines = total pyrimidines).
• Rosalind Franklin's X-ray diffraction (Photo 51): showed DNA was helical with regular spacing.

6.2.1 Components of DNA

DNA is a polymer of nucleotides. Each nucleotide has three parts:

1. Pentose sugar — deoxyribose (5-carbon sugar).
2. Phosphate group.
3. Nitrogenous base — one of four:
   • Purines (double ring): Adenine (A) and Guanine (G).
   • Pyrimidines (single ring): Cytosine (C) and Thymine (T).

6.2.2 Key Features of the Double Helix

• Two polynucleotide strands wound around each other in a right-handed double helix.
• The two strands are antiparallel — one runs 5'→3', the other 3'→5'.
• Sugar-phosphate backbone is outside; bases face inward.
• Complementary base pairing: A pairs with T (via 2 H-bonds), G pairs with C (via 3 H-bonds).
• Pitch (one full turn) = 3.4 nm; ~10 base pairs per turn; rise per base = 0.34 nm.
• Diameter = 2 nm (constant — purine + pyrimidine width is uniform).

6.2.3 Chargaff's Rules

Chargaff's rules were essential clues:

1. Amount of A = Amount of T.
2. Amount of G = Amount of C.
3. Total purines (A + G) = Total pyrimidines (T + C).
4. (A + T) / (G + C) varies between species but is fixed within a species.

Worked Examples