Chapter 16: The Molecular Basis of Inheritance

Concept 16.1: DNA as the Genetic Material

  • Early 20th century: Identifying molecules of inheritance was a major challenge.
  • T.H. Morgan's group: Genes are located on chromosomes. This made DNA and protein, the two components of chromosomes, candidates for the genetic material.
  • The role of DNA in heredity was first discovered by studying bacteria and viruses that infect them.

Evidence That DNA Can Transform Bacteria

  • Frederick Griffith (1928): Discovered the genetic role of DNA while working with two strains of bacterium: pathogenic and harmless.
  • Experiment: Mixed heat-killed pathogenic strain with living harmless strain, some living cells became pathogenic.
  • Transformation: Change in genotype and phenotype due to assimilation of foreign DNA.
Griffith's Experiment

  • Living S cells (pathogenic control): Mouse dies.

  • Living R cells (nonpathogenic control): Mouse healthy.

  • Heat-killed S cells (nonpathogenic control): Mouse healthy.

  • Mixture of heat-killed S cells and living R cells: Mouse dies, living S cells are found.

  • Oswald Avery, Maclyn McCarty, and Colin MacLeod: Identified DNA as the transforming substance.

  • Many biologists were initially skeptical due to limited knowledge about DNA.

Evidence That Viral DNA Can Program Cells

  • More evidence for DNA as genetic material came from studying viruses that infect bacteria (bacteriophages or phages).
  • Virus: DNA (sometimes RNA) enclosed by a protective protein coat.
  • Phages are tools used in molecular genetics research.
Hershey and Chase Experiment (1952)
  • Alfred Hershey and Martha Chase showed that DNA is the genetic material of phage T2.
  • Experiment: Designed to show whether DNA or protein enters an E. coli cell during infection.
  • Conclusion: Injected DNA of the phage provides the genetic information.
Experimental Details
  • Batch 1: Radioactive sulfur (35S^{35}S) in phage protein (pink).
  • Batch 2: Radioactive phosphorus (32P^{32}P) in phage DNA (blue).
  • Labeled phages infect cells.
  • Agitation frees outside phage parts from cells.
  • Centrifuged cells form a pellet.
  • Measured the radioactivity in the pellet and the liquid.
  • Results: Radioactive protein found in liquid, radioactive DNA found in pellet.

Additional Evidence That DNA Is the Genetic Material

  • DNA is a polymer of nucleotides: nitrogenous base, sugar, and phosphate group.
  • Nitrogenous bases: adenine (A), thymine (T), guanine (G), cytosine (C).
  • Erwin Chargaff (1950): DNA composition varies from one species to the next.
  • Molecular diversity made DNA a more credible candidate for genetic material.
Chargaff's Rules
  • Base composition of DNA varies between species.
  • In any species, the number of A and T bases is equal (A=T), and the number of G and C bases is equal (G=C).
  • The basis for these rules wasn't understood until the discovery of the double helix.
DNA Nucleotide Structure
  • Sugar-phosphate backbone.
  • Nitrogenous bases: Thymine, Guanine, Cytosine, Adenine.
  • DNA nucleotide: Phosphate group, sugar (deoxyribose), nitrogenous base.
Building a Structural Model of DNA
  • After DNA was accepted as the genetic material, the challenge was to determine its structure to understand how it accounts for its role in inheritance.
  • Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study molecular structure.
  • Franklin produced a picture of the DNA molecule using this technique.
Franklin's X-Ray Diffraction Photograph
  • Franklin's X-ray crystallographic images of DNA allowed James Watson to deduce that DNA was helical.
  • The X-ray images also enabled Watson to deduce the width of the helix and the spacing of the nitrogenous bases.
  • The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix.
Watson and Crick's Model
  • Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA.
  • Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior.
  • Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions).
DNA Double Helix Dimensions

  • Diameter = 2nm2 nm

  • Bases 0.34nm0.34 nm apart

  • One full turn every 10 base pairs (3.4nm3.4 nm)

  • Initially, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width.

  • Instead, pairing a purine (A or G) with a pyrimidine (C or T) resulted in a uniform width consistent with the X-ray data.

Base Pairing Specificity
  • Watson and Crick reasoned that the pairing was more specific, dictated by the base structures.
  • They determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C).
  • The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C.
Hydrogen Bonds in Base Pairs
  • Nitrogenous base pairs are held together by hydrogen bonds.
  • Adenine (A) pairs with Thymine (T) with two hydrogen bonds.
  • Guanine (G) pairs with Cytosine (C) with three hydrogen bonds.

Concept 16.2: DNA Replication and Repair

  • Offspring resemble parents due to accurate DNA replication before meiosis and transmission to the next generation.
  • Replication before mitosis ensures faithful transmission of genetic information from parent cell to two daughter cells.
  • Watson and Crick noted that specific base pairing suggested a possible copying mechanism for genetic material, called DNA replication.

The Basic Principle: Base Pairing to a Template Strand

  • Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication.
  • This yields two exact replicas of the “parental” molecule.
  • Parental molecule separates, and nucleotides complementary to the parental strand are connected to form new