The Molecular Basis of Inheritance

Chapter 16 - The Molecular Basis of Inheritance

Introduction to DNA

  • Year of Discovery: 1953

  • Key Scientists: James Watson and Francis Crick

  • Model Introduced: Double-helical model for DNA structure.

  • Key Functions of DNA:

    • Encodes hereditary information.

    • Reproduces information in all cells of the body.

    • DNA replication allows for copying and repair of genetic material.

    • Directs the development of biochemical, anatomical, physiological, and some behavioral traits.

The Search for the Genetic Material

  • Key Challenge: Identifying molecules of inheritance in the early 20th century.

  • Contributions of T. H. Morgan:

    • Established that genes are located on chromosomes.

    • Proposed that two components of chromosomes—DNA and proteins—were main candidates for genetic material.

  • Initial Discoveries:

    • Role of DNA in heredity discovered through studies of bacteria and their viruses.

Evidence That DNA Can Transform Bacteria

  • Frederick Griffith's Experiment (1928):

    • Studied two strains of bacteria: one pathogenic (disease-causing) and one nonpathogenic.

    • Transformation Phenomenon: Mixing heat-killed pathogenic bacteria with living nonpathogenic bacteria led some nonpathogenic bacteria to become pathogenic.

    • Transformation defined as a change in genotype and phenotype due to assimilation of foreign DNA.

Experiment Overview: Griffith's Findings

  • Experiment:

    1. Living S cells (pathogenic) → mouse dies.

    2. Living R cells (nonpathogenic) → mouse healthy.

    3. Heat-killed S cells → mouse healthy.

    4. Mixture of heat-killed S cells and living R cells → mouse dies; living S cells detected.

Subsequent Discoveries in DNA Research

  • Avery, McCarty, and MacLeod:

    • Identified the transforming substance as DNA.

    • Skepticism remained about DNA's role as genetic material due to its perceived simplicity.

Evidence From Viral DNA

  • Bacteriophages (Phages):

    • Important in molecular genetics research; consist of DNA or RNA enclosed by a protein coat.

  • Hershey-Chase Experiment (1952):

    • Demonstrated that DNA is the genetic material of phage T2.

    • Experiment showed that only DNA enters bacterial cells during phage infection.

Additional Evidence Supporting DNA as Genetic Material

  • Structure of DNA:

    • DNA is a polymer of nucleotides, each comprising a nitrogenous base, a sugar, and a phosphate.

    • Nitrogenous Bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C).

  • Erwin Chargaff's Rule (1950):

    • Noted variation in DNA composition across species.

    • Two key findings known as Chargaff’s rules:

    1. Base composition varies between species.

    2. In any species, number of A = T, number of G = C.

Structure of DNA Strand

  • Components of DNA Structure:

    • Sugar-phosphate backbone.

    • Orientation: 5' end and 3' end.

    • Hydrogen bonding between bases crucial for structure.

Building a Structural Model of DNA

  • X-ray Crystallography:

    • Used by Maurice Wilkins and Rosalind Franklin to discover DNA structure.

    • Franklin's images suggested that DNA is helical, with specific dimensions and base spacing.

  • Watson and Crick Model:

    • Proposed double helical structure after interpreting X-ray images.

    • Two sugar-phosphate backbones, with bases paired inside—antiparallel.

Base Pairing in DNA

  • Crucial Observations:

    • Consistent width of helix achieved by pairing purines (A, G) with pyrimidines (C, T).

    • Specific Pairing: A pairs with T and G pairs with C.

  • Relation to Chargaff's Rules:

    • Explains the equivalence of A to T and G to C in any organism.

Principles of DNA Replication

  • Semiconservative Model:

    • Each daughter DNA molecule consists of one parent strand and one new strand.

  • Competing Models:

    1. Conservative Model: Two parent strands rejoin.

    2. Dispersive Model: Each strand is a mix of old and new DNA.

  • Meselson & Stahl Experiment:

    • Experimentally demonstrated semiconservative replication.

DNA Replication Process

  • Key Concepts:

    • Begins at origins of replication, creating replication ‘bubbles’.

    • Replication Fork: Y-shaped regions where strands elongate.

    • Key enzymes in initiation: helicases (unwind DNA), single-strand binding proteins (stabilize strands), topoisomerases (relieve strain).

  • Synthesizing a New Strand:

    • DNA polymerases synthesize new strands, requiring a primer to begin addition of nucleotides.

    • RNA primers are utilized to start strand synthesis, synthesized by primase.

Enzymes in DNA Synthesis

  • DNA Polymerase Functions:

    • Add nucleotides at a rate of ~500 nucleotides/sec in bacteria and ~50/sec in human cells.

    • Each nucleotide added is a nucleoside triphosphate (dATP, dGTP, dCTP, dTTP).

    • Incoming nucleotides lose two phosphate groups during DNA strand addition.

  • Antiparallel Elongation:

    • Affects how strands are synthesized.

    • Leading strand synthesized continuously, while lagging strand is synthesized in Okazaki fragments due to its direction.

DNA Excision and Repair Mechanisms

  • Proofreading by DNA Polymerases:

    • Corrects incorrect nucleotides during synthesis.

    • Mismatch Repair: Repair enzymes correct base pairing errors.

    • Nucleotide Excision Repair: Nucleases cut out damaged DNA stretches; DNA polymerases replace them.

Chromosomal Structure

  • Composition of Chromosomes:

    • DNA molecule packaged with proteins to form chromosomes.

    • In bacteria, circular and supercoiled; in eukaryotes, linear associated with more proteins.

  • Chromatin Structure in Eukaryotic Cells:

    • DNA and proteins form chromatin, organized into nucleosomes (beads on a string).

    • Histones play a key role in DNA packing and gene regulation.

Chromatin Dynamics During the Cell Cycle

  • Interphase Chromatin:

    • Exists as 10-nm (extended) and 30-nm (compact) fibers.

    • Condenses into metaphase chromosomes before mitosis.

  • Euchromatin vs Heterochromatin:

    • Euchromatin is less condensed, allows gene expression; heterochromatin is tightly packed, inhibiting gene expression.

  • Histone Modifications:

    • Chemical modifications influence chromatin structure and gene expression (epigenetics).

Summary Points

  • Key Definitions to Note:

    • DNA replication, transformation, bacteriophages, double helix, antiparallel strands, origins of replication, leading strand, lagging strand, Okazaki fragments, mismatch repair, nucleotide excision repair, histones, euchromatin, heterochromatin, epigenetics.

  • Understanding Experiments:

    • Familiarity with various scientists’ contributions to DNA research, their significant experiments, and findings is crucial.

  • Processes in DNA Replication:

    • Detailed knowledge of bacterial DNA replication, including all enzyme functions, proofreading mechanisms, and DNA packaging is essential.

Homework and Class Activity

  • Homework: Due November 3, 2025, via Blackboard with assigned readings from Chapters 16 and 17.

  • In-Class Activity: Group task to draw a bacterial DNA replication bubble with associated proteins and enzymes.