Biology · MU Sofia

15. Mutational variation. Gene mutations. Single-gene disorders.

Covers gene mutations at the level of individual nucleotides, distinguishing transitions from transversions and explaining the chemical and mechanistic causes of each. It then describes frameshift mutations from insertions and deletions, the polymerase slippage model with repeat-sequence examples, and the physical and chemical mutagenic factors that damage DNA.

Inside: 1 section · 1 labelled picture · 3 min

Topic 15 of 64 in the MU Sofia syllabus for Biology (Dental Medicine, Year 1). The free AceMed note covers it in 1 section, about 445 words (3 min of reading).

In this note

  1. Introduction

Introduction

Gene Mutations & Mechanism

  • Basics of Gene Mutations:
  • Changes in nucleotide base transcription from the original strand.
  • Occur approximately once every 100,000 nucleotides.
  • Most mutations are repaired; unrepaired mutations in gametes can be inherited.
  • Mutations occur randomly at the base level.
  • Types of Mutations:
  • Transition Mutations: Purine to purine (A↔G) or pyrimidine to pyrimidine (C↔T).
  • Mechanisms:
  • Tautomerization, influence of chemical analogues, deamination, and nitrous acid (HNO2) as a mutagen.
  • Transversions: Purine to pyrimidine or vice versa, with mechanisms less understood but involving UV light.
  • Synonymous and Nonsynonymous: Impact on the coded amino acid.
  • Frameshift Mutations: Insertions or deletions that alter the DNA sequence.
  • Mechanisms:
  • DNA polymerase errors, slipped strand mispairing during replication.
  • Impact of Mutations:
  • Not all mutations affect the phenotype or are heritable.
  • Mutations causing diseases are termed single gene or "Mendelian disorders" (e.g., cystic fibrosis, sickle cell anemia).

Substitutions

  • Types:
  • Transitions: A purine (A or G) is substituted with a different purine, or a pyrimidine (C or T) is substituted with a different pyrimidine. Example: A→G or C↔T.
  • Transversions: A purine is substituted with a pyrimidine or vice versa, which is less common. Example: A→C or G↔T.
  • Mechanisms:
  • Transitions:
  • Tautomerization and the presence of chemical analogues can cause bases to mispair.
  • Deamination and nitrous acid (HNO2) act as mutagens facilitating transitions.
  • Transversions:
  • Less clearly understood but UV light is known to play a role.

Mechanisms for Insertions and Deletions

  • Chemicals like ethidium bromide and acridine dyes can induce frameshift mutations by altering DNA structure during replication.
  • Slipped strand mispairing can occur during DNA replication, leading to insertions or deletions.

Polymerase Slippage Model

  • Basic Concept: During DNA replication, the polymerase may slip off the template strand, potentially causing duplications or expansions of codons.
  • Process Details:
  • The slippage leads to unpairing between the template strand and the new strand.
  • This slippage is more likely to occur in regions with repeated sequences, like in the Huntington gene.
  • When the new strand attempts to reattach to the template, it might align with the wrong repeat, creating a bubble of unpaired bases.
  • Post-replication, a repair mechanism works to realign the strands correctly.
  • Consequences:
  • The resulting DNA helix may have more repeats of the motif than the original.
  • Such changes can lead to genetic mutations, including deletions or insertions, without the influence of external mutagens.

Mutagenic Factors

  • Types:
  • Physical: Ionizing radiation, UV light, and radioactive decay.
  • Chemical: Oxygenating, deaminating, and alkylating agents.

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