Chapter 13 – Altering the Genetic Material: Mutation and DNA Repair

Chapter 13 – Altering the Genetic Material: Mutation and DNA Repair

1. Consequences of Mutations

• Definition: A mutation is a heritable change in the genetic material.

• Importance: Mutations are essential for the continuity of life, providing variation for natural selection.

• Impact: New mutations are generally more harmful than beneficial.

• DNA Repair: Most DNA damage is reversed by DNA repair systems before it leads to permanent mutations.

• Cancer Link: Cancer can be caused by gene mutations; for example, chemicals in cigarette smoke can mutate DNA, potentially leading to lung cancer.

2. Types of Point Mutations

• Point Mutation: Affects a single base pair within the DNA.

  • Base Substitution: Replacement of one base with another.

  • Example: If T is replaced by G, the complementary A is replaced with C.

  • Base Addition/Deletion: Involves adding or removing a single base pair, causing a mutation.

  • Example: Adding an A-T base pair to the sequence.

3. Effects of Mutations on Polypeptides

• Classification of Point Mutations: Within the coding region, mutations can be classified as:

  • Silent Mutation: No effect on amino acid sequence.

  • Missense Mutation: Changes one amino acid in the sequence.

  • Nonsense Mutation: Creates a premature stop codon.

  • Frameshift Mutation: Alters the reading frame of the gene.

4. Genetic Diseases and Mutations

• Disease Origin: Many human diseases arise from mutations in genes.

• Single Gene vs. Multi-gene Disorders: Some disorders result from mutations in a single gene, while others involve multiple genes.

• Heritability: Mutations in germ-line cells can be passed from parents to offspring, while somatic cell mutations cannot.

5. Mutations in Noncoding Sequences

• Gene Expression: Mutations outside of coding sequences can influence gene expression by affecting regulatory elements.

6. Germ-Line vs. Somatic Mutations

• Types of Cells:

  • Germ-line Cells: Give rise to gametes; mutations here can be inherited.

  • Somatic Cells: All other body cells (not involved in reproduction, meaning they are not sperm or egg cells); mutations here are not passed to offspring

• Timing and Location of Mutations: The severity and heritability of a mutation depend on when and where it occurs in development.

7. Causes of Mutations

• Random Mutations: The Lederbergs' experiment demonstrated that mutations can occur randomly, prior to exposure to environmental factors.

• Spontaneous Mutations: Result from normal biological processes (e.g., errors during DNA replication).

  • Background mutation rate is approximately 1 mutation per 1 million genes.

• Induced Mutations: Caused by environmental mutagens.

  • mutagens: agents that cause mutations in DNA (physical: radiation or chemical: certain chemicals)

8. Types of Mutagens

• Chemical Mutagens: Can covalently modify DNA, act as analogs, or distort DNA structure.

  • Example: Nitrous acid modifies bases, changing C to U.

• Physical Mutagens: X-rays and UV light damage DNA structure.

  • Ionizing Radiation: Causes deletions or breaks in DNA strands.

  • Nonionizing Radiation: UV rays can cause thymine dimers, leading to replication errors.

9. Ames Test for Mutagenicity

• Description: Tests whether a substance is a mutagen using Salmonella typhimurium, which cannot produce histidine due to a mutation.

• Objective: Monitor the mutation rate that restores histidine (amino acids important for protein synthesis and various biological functions) synthesis, indicating mutagenic properties.

10. DNA Repair Systems

• Need for Repair: Essential for organisms to minimize DNA mutations.

• Common Repair System: Nucleotide excision repair (NER) is prevalent in eukaryotes and prokaryotes.

  • Process: Damaged nucleotides are removed, and the intact strand serves as a template for resynthesis.

Summary of Key Concepts

• Mutations: Can be classified by their effects on the coding sequence and can lead to various genetic diseases.

• Causes: Distinguish between spontaneous and induced mutations and understand the role of mutagens.

• DNA Repair: Essential for maintaining genetic integrity and involves sophisticated systems to address damages.