Gene Mutation, DNA Repair, and Transposition – Study Notes

Gene Mutation, DNA Repair, and Transposition

Introduction

This study guide covers the fundamental concepts of gene mutations, their molecular mechanisms, classification based on cellular and functional effects, and the basics of DNA repair. These topics are central to understanding genetic diversity, disease, and cellular responses to DNA damage in genetics.

Gene Mutations

Definition of Gene Mutation

• Gene mutation refers to any alteration in the nucleotide sequence of an organism’s genome.

• Any base-pair change in any part of a DNA molecule is considered a mutation.

• For this discussion, focus is on mutations occurring in DNA genomes.

Cellular Location of Mutations

• Germ line mutations: Occur in germ cells (sperm or egg). These are heritable and form the basis for genetic diversity, evolution, and inherited genetic diseases.

• Somatic mutations: Occur in somatic (body) cells. These are not passed to offspring but can lead to altered cellular function or tumors.

Types of Gene Mutations Based on Molecular Changes

Major Types

• Substitution: A single base in DNA is changed.

• Insertion: One or more extra bases are added to the DNA sequence.

• Deletion: One or more bases are removed from the DNA sequence.

Examples and Effects

• Substitution: THE CAT SAW THE DOG → THE BAT SAW THE DOG (point mutation)

• Deletion: THE CAT SAW THE DOG → THE ATS AWT HED OG (frameshift mutation, loss of C)

• Insertion: THE CAT SAW THE DOG → THE CMA TSAWTH EDO (frameshift mutation, insertion of M)

Frameshift mutations result from insertions or deletions that change the reading frame, often rendering the protein nonfunctional.

Point Mutations

Types of Point Mutations

• Silent mutation: No change in the protein; the new codon still encodes the same amino acid.

• Missense mutation: The change leads to a different amino acid being incorporated into the protein.

• Nonsense mutation: The change creates a premature stop codon, truncating the protein.

Classification Based on Effect on Function

Functional Impact of Mutations

• Loss-of-function mutation: Reduces or eliminates the function of the gene product.

• Null mutation: A mutation resulting in complete loss of function.

• Recessive mutations: Often, loss-of-function mutations are recessive; the wild-type phenotype is maintained if the other allele is normal.

In diploid organisms, less than 100% of gene product may be sufficient for a wild-type phenotype.

Causes of Mutations

Spontaneous vs. Induced Mutations

• Spontaneous mutations: Occur naturally during DNA replication or due to endogenous cellular processes.

• Induced mutations: Result from exposure to external agents (mutagens) such as radiation, chemicals, or viruses.

Spontaneous Errors

• Tautomeric shifts: Temporary changes in base structure leading to mispairing.

• Hydrolytic damage: Includes deamination (loss of NH2 group) and depurination (loss of purine base).

• Alkylation: Addition of alkyl groups to DNA bases.

Induced Mutations

• Radiation: UV (non-ionizing) and ionizing radiation (X-rays, gamma rays, alpha, beta, neutrons).

• Chemicals: Alkylating agents (e.g., mustard gas, EMS, cyclophosphamide) and intercalating agents (e.g., ethidium bromide, acridine orange, proflavin).

• Viruses: Some viruses can integrate into the genome and disrupt normal DNA sequences.

DNA Repair Mechanisms

Overview

Cells possess multiple repair systems to maintain genome integrity. Failure of these systems can lead to accumulation of mutations, cancer, or genetic disorders.

Major DNA Repair Systems

• Proofreading by DNA polymerase: During replication, DNA polymerase corrects mismatched bases.

• Mismatch Repair: Post-replication, enzymes detect and replace mismatched bases missed by proofreading.

• Base Excision Repair (BER): Repairs small mistakes such as damaged or missing bases (e.g., removal of uracil from DNA).

• Nucleotide Excision Repair (NER): Removes and replaces stretches of damaged DNA, such as UV-induced thymine dimers.

• Double-Strand Break Repair: Repairs breaks affecting both DNA strands.

Consequences of Repair Failure

• Accumulation of mutations

• Development of cancer

• Genetic disorders

Summary Table: Types of Gene Mutations

Type	Description	Effect on Protein	Example
Substitution	Single base change	Point mutation (silent, missense, nonsense)	THE BAT SAW THE DOG
Insertion	One or more bases added	Frameshift mutation	THE CMA TSAWTH EDO
Deletion	One or more bases removed	Frameshift mutation	THE ATS AWT HED OG

Key Equations and Concepts

• Central Dogma: $\text{DNA} \rightarrow \text{RNA} \rightarrow \text{Protein}$

• Mutation Rate: $\text{Rate} = k[\text{Mutagen}]$ Additional info: Actual mutation rates depend on the type of mutagen and cellular context.

Additional info:

• Frameshift mutations often result in premature stop codons and nonfunctional proteins.

• DNA repair is essential for preventing disease and maintaining genetic stability.