The Molecular Basis of Inheritance Notes
The Molecular Basis of Inheritance
Chapter Overview
Hereditary information is encoded in DNA and is present in all cells of the body.
DNA's programming directs the development of biochemical, anatomical, physiological, and behavioral traits.
The Search for the Genetic Material: Scientific Inquiry
T. H. Morgan’s group demonstrated that alleles are located on chromosomes.
Chromosomes consist of two components: DNA and protein, both of which were considered candidates for genetic material.
Evidence That DNA Can Transform Bacteria
Frederick Griffith's research in 1928 identified the genetic role of DNA using two strains of bacteria: one pathogenic and one harmless.
Griffith’s Experiment:
He mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain.
Some living cells became pathogenic, which Griffith termed transformation, defined as a change in genotype and phenotype due to the assimilation of foreign DNA.
Experimental Results Fig. 16-2
Control Groups:
Living S cells (pathogenic) → Mouse dies.
Living R cells (harmless) → Mouse healthy.
Heat-killed S cells → Mouse healthy.
Mixture of heat-killed S cells and living R cells → Mouse dies.
Genetic Material: DNA or Proteins?
Bacteriophage T2 Structure:
The bacteriophage consists of a head, tail, and tail fibers, with DNA inside.
Hershey and Chase Experiment (1952)
Alfred Hershey and Martha Chase conducted experiments confirming DNA as the genetic material of the T2 phage.
They designed an experiment to identify which component (DNA or protein) enters E. coli cells during phage infection.
Experimental Setup
Batch 1: Radioactive sulfur () labeled protein.
Batch 2: Radioactive phosphorus () labeled DNA.
Additional Evidence That DNA Is the Genetic Material
DNA is a polymer of nucleotides, each made of a nitrogenous base, a sugar, and a phosphate group.
Chargaff's Contribution (1950): DNA composition varies among species, providing evidence for diversity and support as the genetic material.
**Chargaff’s Rules:
A = T and G = C** (equal amounts of adenine and thymine, and guanine and cytosine in any given organism).
Structural Model of DNA
Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study DNA's structure, leading to critical insights.
Franklin's X-ray diffraction images showed that DNA was helical, defining its width and nitrogenous base spacing.
Watson and Crick's Double-Helical Model (1953)
Watson and Crick proposed that:
DNA is a double helix with two antiparallel sugar-phosphate backbones and nitrogenous bases paired in the interior.
The base pairing hypothesis: adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C).
Explanation of Base Pairing
Initial assumption (by Watson and Crick) was incorrect model of base pairing (e.g., A with A).
Correct model: Purine (A, G) pairs with pyrimidine (C, T) to maintain uniform width of the double helix.
This pairing is specific and aligns with Chargaff's observations.
Structural Features of DNA
Key structural aspects include:
The antiparallel orientation of the two strands: one runs 5' to 3', while the other 3' to 5'.
Base pairs are held together by hydrogen bonds, maintaining the double-helical structure.
DNA Replication Overview
Base Pairing to a Template Strand:
Each strand of DNA serves as a template for synthesizing the new strand during replication.
Replication proceeds by unwinding the double helix at the replication fork, generating daughter strands.
Semiconservative Model of Replication
During replication, the parent strand unwinds and each strand acts as a template for creating new daughter strands.
Experiment by Meselson and Stahl:
Used heavy and light nitrogen isotopes to prove that DNA replication is semiconservative.
Detailed Mechanism of DNA Replication
**Enzymatic Roles:
Helicases:** Untwist the double helix.
Single-strand Binding Proteins: Stabilize single-stranded DNA.
Topoisomerase: Manages DNA over-winding.
Primase: Synthesizes RNA primers to initiate the replication process.
DNA Polymerases: Catalyze the addition of nucleotides to elongate new DNA strands; requires a primer.
DNA Ligase: Joins Okazaki fragments on the lagging strand.
Antiparallel Elongation
The antiparallel nature of DNA means replication occurs in a specific direction (only 5' to 3').
DNA polymerase synthesizes the leading strand continuously, while the lagging strand forms discontinuously in Okazaki fragments, which are later joined by DNA ligase.
DNA Proofreading and Repair Processes
DNA polymerases possess proofreading capabilities to correct errors in nucleotide incorporation.
Mismatch repair enzymes rectify base-pairing mistakes.
Nucleotide excision repair involves cutting out and replacing damaged DNA regions.
Challenges of Replicating Linear DNA
DNA polymerase can’t fully replicate the ends of linear DNA, leading to chromosomal shortening with each replication.
Telomeres: Specialized structures at the ends of linear chromosomes that protect genes from erosion.
Telomerase enzyme extends telomeres in germ cells, possibly linking telomere shortening to aging and cancer risk.
Implications of Telomere Shortening
Shortened telomeres may prevent cell division, offering a protective mechanism against cancer, while their maintenance by telomerase in cancer cells could allow for unchecked growth.