Chapter 13: Molecular Basis of Inheritance

Key Topic: DNA Structure and Discovery

• Focus on structure of DNA and identification of DNA as genetic material.
• Historical context: Experiments began a little over a century ago.

Historical Experiments and Discoveries

Thomas Hunt Morgan

• Proved genes are located on chromosomes using fruit flies (Drosophila).
• Raised the question: Is DNA or protein the genetic material?

Frederick Griffith (1928)

• Worked with two strains of bacteria (R: rough, harmless; S: smooth, pathogenic).
• Experimented with mice, demonstrating transformation:
  • Living S cells killed mice.
  • R cells did not kill mice; heat-killed S cells alone did not kill.
  • Mixture of heat-killed S and living R cells killed the mice, transforming R into pathogenic S.
• Introduced the "Principle of Transformation": genetic material transfer between bacterial strains.

Avery, MacLeod, and McCarty

• Built on Griffith's work.
• Supported DNA as the "transforming principle" but results were initially not widely accepted.

Hershey and Chase (1952)

• Used bacteriophages to demonstrate DNA as genetic material:
  • Tagged proteins with radioactive sulfur.
  • Tagged DNA with radioactive phosphorus.
  • Found DNA entered cells, not protein, proving DNA is genetic material.

DNA Structure and Base Pairing

Chargaff's Rules

• Erwin Chargaff: Discovered base pair rules.
• A=T and C=G in DNA samples.
• Important for determining DNA structure.

Rosalind Franklin and Maurice Wilkins

• Used X-ray crystallography to photograph DNA.
• Franklin’s Photo 51 suggested DNA was helical.

Watson and Crick

• Built the first model of DNA double helix in 1953.
• Combined Franklin’s images and Chargaff's rules.
• DNA structure: Double helix with sugar-phosphate backbone and base pairs (A-T, G-C) in the center.
• Nobel Prize awarded to Watson, Crick, and Wilkins.

DNA Replication

Watson and Crick's Semi-Conservative Model

• Hypothesized DNA strands separate and each serves as a template, forming molecules half old, half new.
• Concept of "semi-conservative" replication: saving half of the original molecule.

Alternative Models

• Conservative Model: Entire original helix conserved.
• Dispersive Model: Mixed old and new DNA.

Meselson and Stahl Experiment

• Supported semi-conservative replication.
• Used nitrogen isotopes to show DNA strands replicated in a manner consistent with semi-conservative model.

Summary

• Historical experiments confirmed DNA as genetic material and elucidated its double helical structure.
• Understanding DNA opened pathways to explore genetic coding and inheritance.
• Important for understanding molecular biology and genetics.