Chapter 16 The Molecular Basis of Inheritance

Lecture Presentations by Nicole Tunbridge and Kathleen Fitzpatrick on The Molecular Basis of Inheritance

Chapter 16: The Molecular Basis of Inheritance

Life’s Operating Instructions

  • Year: 1953
  • Key Figures: James Watson and Francis Crick
  • Contribution:
    • Introduced a double-helical model for the structure of DNA (deoxyribonucleic acid).
    • Hereditary information is encoded in DNA and reproduced in all cells of the body.
    • This DNA program directs the development of biochemical, anatomical, physiological, and to some extent, behavioral traits.

Concept 16.1: DNA is the Genetic Material

  • The understanding and identification of the molecular carriers of heredity posed a significant challenge in the early 20th century.

The Search for the Genetic Material: Scientific Inquiry

  • Key Researcher: T.H. Morgan
    • Contributions by Morgan's group indicated that genes are located on chromosomes.
    • Chromosome components: DNA and protein, both emerged as candidates for the genetic material.
  • Findings:
    • The role of DNA as hereditary material was initially discovered through studies involving bacteria and bacteriophages (viruses that infect bacteria).

Evidence That DNA Can Transform Bacteria

  • Key Researcher: Frederick Griffith (1928)
    • Studied two strains of bacteria: pathogenic strain and harmless strain.
  • Griffith's Experiment:
    • Mixed heat-killed pathogenic strain with live harmless strain.
    • Result:
    • Transformation occurred; some harmless cells became pathogenic.
    • Definition of Transformation:
    • A change in genotype and phenotype due to assimilation of foreign DNA.

Figure 16.2: Griffith's Transformation Experiment Results

  • Controls:
    • Living S cells (pathogenic): Mouse dies.
    • Living R cells (nonpathogenic): Mouse healthy.
    • Heat-killed S cells: Mouse healthy.
    • Mixture of heat-killed S cells and living R cells: Mouse dies.

Identification of DNA as Transforming Substance

  • Subsequent work by Oswald Avery, Maclyn McCarty, and Colin MacLeod confirmed that the transforming substance was DNA.
  • Skepticism: Many biologists were initially doubtful, as knowledge of DNA was still limited.

Evidence That Viral DNA Can Program Cells

  • Type of Virus: Bacteriophages (or phages).
    • Structure: Virus comprised of DNA (sometimes RNA) encased in a protein coat.
  • Key Researchers: Alfred Hershey and Martha Chase (1952)
    • Experiment designed to determine whether DNA or protein entered E. coli cells during bacteriophage infection.
  • Conclusion: Injected DNA provides the genetic information.

Figure 16.4: Hershey-Chase Experiment

  • Experiment Steps:
    • Labeled phages with radioactive markers (sulfur for protein, phosphorus for DNA).
    • Phage infects bacterial cells, followed by agitation to free outside phage parts.
    • Cells are centrifuged, measuring radioactivity in pellet and liquid.

Additional Evidence from Chargaff’s Research

  • DNA Composition:
    • DNA is a polymer of nucleotides (nitrogenous base, sugar, phosphate).
    • Nitrogenous bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C).
  • Chargaff’s Findings (1950):
    • Variation in base composition among species confirmed DNA's role as the genetic material.
  • Chargaff’s Rules:
    • In any species, the number of adenine (A) equals thymine (T) and the number of guanine (G) equals cytosine (C).

Building a Structural Model of DNA

  • Following the acceptance of DNA as genetic material, researchers sought to understand its structural implications for heredity.
  • Key Contributors: Maurice Wilkins and Rosalind Franklin
    • Used X-ray crystallography to analyze DNA's molecular structure.
    • Franklin’s X-ray images led to the conclusion of DNA's helical structure, spacing, and strand formation.

Structural Details of DNA: Watson and Crick Model

  • Key Observations: Every full turn of the helix consists of 10 base pairs (3.4 nm). Height between bases is 0.34 nm, with a diameter of 2 nm.
  • Backbone Structure:
    • Composed of two sugar-phosphate backbones with nitrogenous bases on the inside.
  • Antiparallel Nature: The two strands are oriented in opposite directions (5' to 3' and 3' to 5').
  • Base Pairing:
    • Adenine pairs with Thymine; Guanine pairs with Cytosine to maintain a uniform width consistent with X-ray data.

Concept 16.2: Many Proteins Work Together in DNA Replication and Repair

  • The specificity in base pairing suggests a copying mechanism for genetic material.

Basic Principles of DNA Replication

  • During DNA replication, two strands separate and serve as templates for the synthesis of new complementary strands.
  • Watson and Crick's Semiconservative Model:
    • Predicts that each daughter DNA molecule contains one old and one new strand, contrasting with the conservative (parent strands rejoin) and dispersive models (mixed strands).

Experiments Supporting the Semiconservative Model

  • Key Researchers: Matthew Meselson and Franklin Stahl.

DNA Replication Process

  • Begins at origins of replication.
  • Replication Fork: Y-shaped region with actively elongating new DNA strands.
  • Enzymes involved in the process:
    • Helicases: Unwind the DNA double helix.
    • Single-Strand Binding Proteins: Stabilize single strands.
    • Topoisomerase: Relieves strain from twisting DNA strands during replication.

Synthesizing a New DNA Strand

  • Primase: Synthesizes short RNA primers required for DNA polymerases.
  • DNA polymerases: Catalyze the addition of nucleotides to growing strands. Most require a primer and template strand.

Rate of DNA Elongation

  • Rate:
    • Bacteria: Approximately 500 nucleotides/sec
    • Human cells: Approximately 50 nucleotides/sec
  • Each nucleotide is added as a nucleoside triphosphate (dATP, dGTP, dCTP, dTTP).
  • Upon joining a DNA strand, nucleotides release two phosphate groups as pyrophosphate via a dehydration reaction.

Antiparallel Elongation of DNA

  • New DNA strands can elongate only in the 5' to 3' direction.
  • Leading Strand: Continuously synthesized towards the replication fork.
  • Lagging Strand: Synthesized discontinuously in segments known as Okazaki fragments, later joined by DNA ligase.

Proofreading and Repairing DNA

  • DNA Polymerases: Proofread new DNA to correct errors.
  • Mismatch Repair: Repair enzymes correct base-pairing mistakes.
  • Nucleotide Excision Repair: A nuclease cuts and replaces damaged DNA.

Evolutionary Significance of Mutations

  • Post-repair, some mutations remain and can be transmitted to future generations, fostering genetic diversity.

Telomeres and Eukaryotic DNA Replication

  • Problem with Linear DNA: Typical replication machinery does not replicate the 5' ends adequately, leading to shortening with each replication cycle.
  • Telomeres: Specialized nucleotide sequences at the ends of eukaryotic chromosomes, which delay erosion of essential genes.
  • Telomerase: Enzyme that extends telomeres in germ cells, potentially linked to aging and cancer cell persistence.

Concept 16.3: Structure of Chromosomes

  • Bacterial Chromosomes: Circular, double-stranded DNA associated with minimal protein.
  • Eukaryotic Chromosomes: Linear DNA intricately packaged with proteins (chromatin).
  • Histones: Proteins facilitating the first level of chromatin packing, appearing as "beads on a string" (nucleosomes).

Changes in Chromatin Packing

  • Chromatin undergoes condensation during the cell cycle, remaining loosely packed (euchromatin) during interphase, while certain regions become densely packed (heterochromatin). This influences gene expression.

Chemical Modifications of Histones

  • Histone tails undergo modifications affecting condensation and gene expression, emphasizing the dynamic nature of chromatin structure.

Notes compiled from © 2017 Pearson Education, Inc.