Ch 16. The Molecular Basis of Inheritance: DNA Structure, Replication, and Chromosome Organization

The Molecular Basis of Inheritance

Introduction

The molecular basis of inheritance centers on the role of DNA as the genetic material. This chapter explores the evidence supporting DNA as the hereditary molecule, its structure, the mechanism of DNA replication, and the organization of DNA within chromosomes.

DNA as the Genetic Material

Historical Experiments Demonstrating DNA's Role

• Griffith's Transformation Experiment (1928): Demonstrated that a substance from dead pathogenic bacteria could genetically transform living nonpathogenic bacteria, suggesting a "transforming principle."

• Hershey-Chase Experiment (1952): Used bacteriophages labeled with radioactive isotopes to show that DNA, not protein, is the genetic material that enters bacterial cells and directs viral replication.

Structure of DNA

DNA Composition and Base Pairing

• DNA is a polymer of nucleotides, each consisting of a nitrogenous base (adenine, thymine, guanine, cytosine), a deoxyribose sugar, and a phosphate group.

• Chargaff's Rules: The amount of adenine (A) equals thymine (T), and the amount of guanine (G) equals cytosine (C).

• Watson and Crick Model: DNA is a double helix with specific base pairing: A pairs with T, and G pairs with C, held together by hydrogen bonds.

Double Helix Structure

• Antiparallel Strands: The two DNA strands run in opposite directions (5' to 3' and 3' to 5').

• Helical Parameters: One full turn every 10 base pairs (3.4 nm), with a diameter of 2 nm.

• X-ray Crystallography: Rosalind Franklin's X-ray diffraction images were critical in elucidating the helical structure of DNA.

DNA Replication

Models of DNA Replication

• Semiconservative Model: Each new DNA molecule consists of one parental strand and one newly synthesized strand. Supported by Meselson and Stahl's experiments.

• Other Models: Conservative (parental molecule conserved) and dispersive (mixed segments) were disproven.

Mechanism of DNA Replication

Replication begins at origins of replication, forming replication bubbles that expand in both directions. At the replication fork, several enzymes coordinate the unwinding and synthesis of new DNA strands.

• Helicase: Unwinds the DNA double helix.

• Single-strand binding proteins: Stabilize unwound DNA.

• Topoisomerase: Relieves strain ahead of the replication fork.

• Primase: Synthesizes short RNA primers.

• DNA Polymerase: Adds nucleotides to the 3' end of the primer, synthesizing new DNA in the 5' to 3' direction.

• Leading Strand: Synthesized continuously toward the replication fork.

• Lagging Strand: Synthesized discontinuously as Okazaki fragments, later joined by DNA ligase.

Enzymes and Proteins in DNA Replication

Protein	Function
Helicase	Unwinds parental double helix at replication forks
Single-strand binding protein	Binds to and stabilizes single-stranded DNA
Topoisomerase	Relieves overwinding strain ahead of replication forks
Primase	Synthesizes RNA primer at 5' ends
DNA polymerase III	Using parental DNA as template, synthesizes new DNA strand by adding nucleotides to an RNA primer or pre-existing DNA strand
DNA polymerase I	Removes RNA nucleotides of primer and replaces them with DNA nucleotides
DNA ligase	Joins Okazaki fragments of lagging strand; joins 3' end of DNA that replaces primer to rest of leading strand DNA

Antiparallel Elongation and Okazaki Fragments

• Antiparallel Structure: DNA polymerases can only add nucleotides to the 3' end, resulting in continuous synthesis on the leading strand and discontinuous synthesis on the lagging strand.

• Okazaki Fragments: Short DNA fragments synthesized on the lagging strand, later joined by DNA ligase.

Proofreading and Repair of DNA

DNA Polymerase Proofreading

• Proofreading: DNA polymerases check and correct mismatched nucleotides during replication.

• Mismatch Repair: Other enzymes remove and replace incorrectly paired nucleotides.

• Nucleotide Excision Repair: Damaged DNA segments are cut out by nucleases and replaced using the undamaged strand as a template.

Evolutionary Significance of Mutations

• Mutations: Permanent changes in DNA sequence that can be inherited. They are the source of genetic variation and drive evolution by natural selection.

Chromosome Structure and DNA Packing

Bacterial Chromosome Organization

• Bacterial Chromosome: Double-stranded, circular DNA molecule with minimal protein association, found in the nucleoid region and supercoiled for compaction.

Eukaryotic Chromosome Organization

• Chromatin: DNA is combined with proteins (mainly histones) to form chromatin, which undergoes multiple levels of packing.

• Nucleosome: The basic unit of DNA packing, consisting of DNA wound around histone proteins.

• Higher-Order Packing: Nucleosomes coil to form 30-nm fibers, which further loop and fold to form metaphase chromosomes.

Chromosome Territories in the Nucleus

• Interphase Chromosomes: Occupy specific regions within the nucleus, preventing entanglement and facilitating regulated gene expression.

Additional info: This guide covers the essential concepts of DNA structure, replication, repair, and chromosome organization, as outlined in Chapter 16: The Molecular Basis of Inheritance. It is suitable for exam preparation and foundational understanding in college-level biology.