Genetics: Mutation and Mutagens

Mutations, Mutagens, and Types of Mutations

Introduction to Mutations

• Mutations are permanent changes in the genetic material of a cell that may or may not affect phenotype
• Mutations can be beneficial, neutral, or harmful
• Beneficial mutations lead to evolutionary changes and adaptation to changing environments
• Neutral mutations have no effect on the fitness of the organism
• Harmful mutations cause human diseases and disorders

Classifications of Mutations

• Based on cause:
  • Spontaneous mutation: occurs naturally due to errors during DNA replication
  • Induced mutation: occurs due to exposure to environmental agents (mutagens)
• Based on tissue/cell of origin:
  • Germline mutation: occurs in gametes and can be passed onto offspring
  • Somatic mutation: occurs in a single body cell and cannot be inherited
• Based on where the mutation occurs:
  • Gene mutation: occurs in a gene
  • Chromosomal mutation: occurs in a chromosome

Germline and Somatic Mutations

• Germline mutation: occurs in gametes, every cell in the entire organism is affected
• Somatic mutation: occurs in a single body cell, only tissues derived from mutated cells are affected

Spontaneous and Induced Mutations

• Spontaneous mutation: occurs naturally due to errors during DNA replication, rate of 10-8 to 10-10 per gene per generation
• Induced mutation: occurs due to exposure to environmental agents (mutagens)

Mutagens

• Environmental agents that increase the rate of mutation
• Three types of mutagens:
  • Physical mutagens
  • Chemical mutagens
  • Biological mutagens

Physical Mutagens

• Physical mutagens include sources of electromagnetic radiation, heat, and ionizing radiation
• Examples:
  • Ionizing radiation (x-rays and gamma rays) can cause ring opening and fragmentation of bases
  • Non-ionizing radiation (UV rays) can lead to cross-linking and generation of nucleotide dimers
  • Heat above 95°C causes DNA denaturation

Chemical Mutagens

• Chemical mutagens alter the structure of DNA
• Examples:
  • Base analogs: incorporated into DNA instead of normal bases, leading to mutation
  • Alkylating agents: alter certain bases of DNA
  • Intercalating agents: disrupt DNA structure by intercalating between bases
  • Deaminating agents: cause the loss of exocyclic amino groups of nucleotide bases
  • Metal ions: produce reactive oxygen species that damage DNA

Biological Mutagens

• Biological mutagens include viruses, bacteria, and transposons
• Examples:
  • Viruses: insert their DNA into the genome, disrupting normal function
  • Bacteria: cause inflammation, leading to DNA damage and breakage
  • Transposons: non-coding DNA sequences that jump from one place to another, influencing gene function

Gene Mutation

• Gene mutations are changes in the nucleotide sequence of DNA
• Two types of gene mutations:
  • Point mutation
  • Frameshift mutation

Point Mutations

• Point mutation: a single nucleotide base pair change
• Examples:
  • Silent mutation: has no effect on the structure and function of the protein
  • Nonsense mutation: causes a codon to become a termination codon
  • Missense mutation: changes the codon to code for a different amino acid

Frameshift Mutations

• Frameshift mutation: addition or removal of a nitrogenous base from a gene
• Results in the translation of the genetic code in an unnatural reading frame
• Examples:
  • Frameshift-deletions: seen in cystic fibrosis, a hereditary disease
  • Frameshift-insertions: changes the number of DNA bases in a gene, affecting protein function

Chromosomal Mutations

• Chromosomal mutations involve a change in the structure or number of chromosomes
• Two types of chromosomal mutations:
  • Chromosomal aberrations
  • Aneuploidy

Chromosomal Aberrations

• Changes in chromosomal structure
• Examples:
  • Chromosomal deletions
  • Chromosomal duplications
  • Chromosomal translocations

Aneuploidy

• Aneuploidy: a change in the number of chromosomes
• Examples:
  • Nullisomy: loss of one homologous chromosome pair
  • Monosomy: loss of a single chromosome
  • Trisomy: one extra chromosome, e.g. Down's syndrome
  • Tetrasomy: an extra chromosome pair