Chapter 16: The Molecular Basis of Inheritance

Introduction

This chapter explores the molecular foundation of inheritance, focusing on the discovery, structure, replication, and repair of DNA. Understanding these processes is essential for grasping how genetic information is stored, transmitted, and maintained in living organisms.

Section 16.1: DNA is the Genetic Material

Historical Foundations of Inheritance

• Mendel’s Laws of Inheritance: Established the basic principles of heredity through experiments with pea plants.

• Chromosomal Theory of Inheritance: Linked Mendel’s laws to the behavior of chromosomes during cell division.

Griffith’s Transformation Experiment

• Transformation: A process where a cell takes up foreign DNA, resulting in a change in genotype and phenotype.

• Griffith showed that harmless bacteria could become pathogenic by acquiring genetic material from dead, disease-causing bacteria.

• Significance: Provided the first evidence that a "transforming principle" (later identified as DNA) could transfer genetic traits.

• Example: Live rough (non-pathogenic) bacteria became smooth (pathogenic) after exposure to heat-killed smooth bacteria.

Hershey-Chase Experiment

• Bacteriophage: A virus that infects bacteria, composed of a protein coat and DNA.

• Used radioactive labeling to distinguish DNA from protein.

• Key Finding: Only DNA entered bacterial cells and directed viral replication, confirming DNA as the genetic material.

Chargaff’s Rules

• DNA composition varies between species.

• The amount of adenine (A) is roughly equal to thymine (T), and cytosine (C) is roughly equal to guanine (G).

• This complementary base pairing is fundamental to DNA structure.

Rosalind Franklin and Photo 51

• Used X-ray crystallography to reveal the helical structure of DNA.

• Photo 51 provided critical measurements for the double helix model, including the width and periodicity of the helix.

Watson and Crick’s DNA Model

• Proposed the double helix structure of DNA.

• DNA is composed of two antiparallel strands held together by complementary base pairs (A-T, C-G).

• The antiparallel arrangement allows for accurate replication and function.

Section 16.2: DNA Replication and Repair

Models of DNA Replication

• Semiconservative Replication: Each new DNA molecule consists of one old (parental) strand and one newly synthesized strand.

• Meselson-Stahl Experiment: Used isotopic labeling to demonstrate that DNA replication is semiconservative.

Origin of Replication and Replication Fork

• Origin of Replication: Specific DNA sequence where replication begins.

• Bacteria have a single origin; eukaryotes have multiple origins per chromosome.

• Replication Fork: The Y-shaped region where the DNA double helix is unwound for replication.

• Leading Strand: Synthesized continuously in the direction of the fork.

• Lagging Strand: Synthesized discontinuously in short segments called Okazaki fragments.

Enzymes of DNA Replication

• Helicase: Unwinds the DNA double helix at the replication fork.

• Topoisomerase: Relieves tension ahead of the replication fork.

• Primase: Synthesizes short RNA primers to provide a starting point for DNA synthesis.

• DNA Polymerase III: Adds nucleotides to the growing DNA strand.

• DNA Polymerase I: Removes RNA primers and replaces them with DNA.

• DNA Ligase: Seals gaps between Okazaki fragments, forming a continuous strand.

Mechanism of DNA Polymerase

• DNA polymerase adds nucleotides to the 3’ OH end of the growing strand.

• Energy for bond formation comes from the hydrolysis of nucleoside triphosphates.

• Pyrophosphate release makes the reaction energetically favorable and irreversible.

Types of Point Mutations

• Silent Mutation: No change in amino acid sequence.

• Missense Mutation: Changes one amino acid; can be conservative (similar properties) or non-conservative (different properties).

• Nonsense Mutation: Introduces a premature stop codon, truncating the protein.

DNA Repair Mechanisms

• Proofreading: DNA polymerase checks and corrects errors during replication.

• Mismatch Repair: Enzymes recognize and replace incorrectly paired bases after replication.

Thymine Dimers and Nucleotide Excision Repair

• Thymine Dimers: UV light can cause covalent bonds between adjacent thymine bases, distorting the DNA helix.

• This distortion blocks DNA polymerase, potentially causing mutations.

• Nucleotide Excision Repair: Specialized enzymes (nucleases) remove damaged DNA, which is then resynthesized and sealed by DNA polymerase and ligase.

Telomeres and Telomerase

• Telomeres: Repetitive, non-coding DNA sequences at chromosome ends that protect genetic material from degradation.

• Telomeres shorten with each cell division in most somatic cells, limiting the number of divisions.

• Telomerase: An enzyme that extends telomeres in germ cells, allowing for full-length chromosome inheritance.

• Cancer cells often reactivate telomerase, contributing to uncontrolled cell division.

Section 16.3: Chromosome Structure and Packaging

Chromosome Packaging

• DNA is wrapped around histone proteins to form nucleosomes ("beads on a string").

• Nucleosomes coil into a 30-nm fiber, which loops and folds further to form the compact structure of chromosomes.

• Linker histones help stabilize higher-order folding.

Active vs. Inactive Chromatin

• Heterochromatin: Densely packed, transcriptionally inactive DNA.

• Euchromatin: Loosely packed, transcriptionally active DNA.

• Chromatin structure is a key mechanism for regulating gene expression (epigenetics).