Chapter 13: Gene Mutations and DNA Repair

13.1 Definition of Mutations

• Mutations are defined as inherited alterations in the DNA sequence.

13.2 Causes of Mutations

• Mutations may arise from a variety of factors.

Chapter 13 Key Terms

• Mutation Types:
    - Mutation
    - Base substitution
    - Missense mutation
    - Mutation rate
    - Transposable element
    - Somatic mutation
    - Transition
    - Nonsense mutation
    - Spontaneous mutation
    - Flanking direct repeat
    - Direct repair
    - Germ-line mutation
    - Transversion
    - Silent mutation
    - Induced mutation
    - Terminal inverted repeat
    - Base-excision repair
    - Gene mutation
    - Insertion
    - Neutral mutation
    - Incorporated error
    - Transposition
    - Nucleotide-excision repair
    - Forward mutation
    - Deletion
    - Loss-of-function mutation
    - Replicated error
    - Transposase
    - Reverse mutation (reversion)
    - Frameshift mutation
    - Gain-of-function mutation
    - Strand slippage
    - DNA transposon
    - Suppressor mutation
    - In-frame insertion
    - Conditional mutation
    - Unequal crossing over
    - Retrotransposon
    - Intragenic suppressor mutation
    - In-frame deletion
    - Lethal mutation
    - Depurination
    - Replicative transposition
    - Intergenic suppressor mutation
    - Expanding nucleotide repeat
    - Deamination
    - Nonreplicative transposition

Importance of Mutations

• Mutations are considered both beneficial and detrimental:
    - They sustain life and cause significant suffering.
    - They serve as the source of all genetic variation, which is crucial for evolution.
    - Mutations are also responsible for many diseases and disorders.
    - Useful for probing fundamental biological processes.

Think-Pair-Share Discussion

Question: Are mutations good or bad?

• Considered “good” for evolution due to adaptation.

• Serve as tools for understanding biological processes and genetic crosses.

• Considered “bad” due to their association with diseases and disorders, causing human suffering.

• Allow pathogens to adapt against treatments such as antibiotics and vaccines.

• Conclusion: Mutations have both positive and negative aspects.

Categories of Mutations

• Somatic Mutations:
    - Occur in nonreproductive cells.
    - Passed via mitosis, creating clones of cells with the mutant gene.

• Germ-Line Mutations:
    - Occur in cells that give rise to gametes.
    - Passed to approximately half the members of the next generation through meiosis and sexual reproduction.

Types of Gene Mutations (Molecular Nature)

• Base Substitutions:
    - Transitions
    - Transversions

• Insertions and Deletions:
    - Frameshift mutations
    - In-frame insertions and deletions

Basic Types of Gene Mutations

• Base Substitution: Alters a single codon.
    - Original DNA Sequence:
      - GGG AGT GTA GAT CGT
    - After Base Substitute:
      - GGG AGT GCA GAT CGT
  

• Nucleotide Insertion: Alters the reading frame; may change multiple codons.
    - Example:
      - Original with insertion: GGG AGT GTT AGA TCG T

• Nucleotide Deletion: Alters the reading frame; may also cause multiple changes.
    - Example:
      - Original with deletion: GGG AGT GAG ATC GT

Transition vs. Transversion

• Transition:
    - Substitution of a purine for a purine or pyrimidine for a pyrimidine.
    - Possible base changes: A ↔ G or C ↔ T.
    - Minimal distortion of DNA structure due to similar base type.

• Transversion:
    - Substitution of a purine for a pyrimidine or vice versa.
    - Possible base changes: A/G ↔ C/T.
    - Larger structural change leading to distortion of the DNA helix.

Types of Gene Mutations: Expanding Nucleotide Repeats

• Involves an increase in the number of copies of a nucleotide set.

Examples of Human Genetic Diseases from Expanding Nucleotide Repeats

Mechanism of Increasing Nucleotide Repeats During Replication

1. Initial molecule has multiple copies of a repeat.

2. The DNA strands separate for replication.

3. Strand parts may replicate twice leading to increased copies on new strand.

4. A hairpin forms, which causes the additional replication of the repeat.

5. Resultant DNA may contain significantly more repeats on the newly synthesized strand.

Phenotypic Effects of Mutations

• Forward Mutation: Conversion from wild type to mutant type.

• Reverse Mutation: Conversion from mutant type back to wild type.

• Missense Mutation: Changes an amino acid to a different one.

• Nonsense Mutation: Alteration of a sense codon to a stop codon.

• Silent Mutation: Codon changes to synonymous codon.

• Neutral Mutation: No change in function occurs.

Comparison of Transition and Transversion