Understanding Genetic Mutations: Types, Causes, and Repair Mechanisms

Posted on Mar 28, 2025 in Biology

Mutations: An Overview

Mutations: Genetic material randomly modifies, which is of great importance in evolution.

Somatic cell mutations do not pass to descendants.

Germline cell mutations can be passed on and fixed in offspring.

  1. Negative mutations can be lethal.
  2. Beneficial mutations drive evolution.

Mutagenic agents can be physical, chemical, or biological.

Types of Mutations

  • Gene mutations: Affect the gene.
  • Chromosomal mutations: Affect chromosomal structure.
  • Genomic mutations: Affect the number of chromosomal sets.

Gene Mutations

Gene mutations are important in evolution.

They alter the nucleotide sequence of a gene randomly.

Types of Gene Mutations:
  1. Replacements:
    1. Transition: Purine replaced by purine, or pyrimidine by pyrimidine.
    2. Transversion: Purine replaced by pyrimidine, or pyrimidine by purine.
  2. Insertions: Introduce a new nucleotide into the sequence.
  3. Deletions: Loss of a nucleotide sequence.

Silent mutations (no variation in the protein) occur in exons and introns.

Conservative mutations: Amino acids are similar.

Non-conservative mutations: Amino acids are different and belong to the active site.

Chromosomal Mutations

Types of Chromosomal Mutations:
  1. Deletions: Lost segment of a chromosome (e.g., A/B/D/E).
  2. Inversion: Affects centromeres (pericentric inversions) or segments (paracentric inversions). Anomalous meiosis occurs (e.g., A/B/D/C/E).
  3. Duplication: A/B/B/C.
  4. Translocation: Change of position of a chromosome segment (same chromosome or another chromosome).

Genomic Mutations

  1. Euploidy: Change in the number of chromosomal sets.
    • Haploidy: Species is n.
    • Polyploidy: Species is 3n, 4n, and so on.

    If meiosis does not occur, gametes are fertilized with another 3n or 4n.

  2. Aneuploidy: Alters the number of homologous chromosome pairs (other than 2). Can have 0 (nullisomy), one (monosomy), 3, etc. Can affect:
    • Autosomes: Down Syndrome.
    • Heterosomes: X0 (Turner Syndrome), XXX, XXY (Klinefelter Syndrome), XYY.

Mutagens

Mutagens may be carcinogenic.

Endogenous Mutagens

Endogenous mutagens occur naturally in cells and are responsible for spontaneous mutations.

  1. Metabolite reagents: Can alter DNA. Free radicals affect OH and O2.
  2. Thermal changes (above 34°C): Cause substitution mutations (in BN and depurinations, deaminations (loss of purine bases)).
  3. Replication Errors:
    1. Tautomeric bases (in equilibrium) are produced by transition base substitution: A (tautomeric) ? C, G (tautomeric) ? T.
    2. Changes based on hot spots where there is repetition of one base.
  4. Transposons: Genes that move around in the genome.

Exogenous Mutagens

  1. Physical:
    1. Non-ionizing radiation (UV).
    2. Ionizing radiation (x-rays and gamma).
    3. α and β corpuscular radiation.
  2. Chemical:
    1. Base analogs (in replication can replace BN).
    2. Alkylating agents (introduce alkyl groups in the BN).
    3. NO2, sodium bisulfite (modified bases are different).
    4. Benzopyrene, dioxins, etc.
  3. Biological:
    1. Oncoviruses (capable of producing a tumor).
    2. Retroviruses (more significant).
    3. Bacteria.

DNA Repair Systems

  1. Direct Repair

    Photoactive enzymes uncouple dimers of T or C.

  2. Excision Repair
    1. Recognizes the error.
    2. Endonuclease: Cuts on both sides.
    3. Exonuclease: Removes the damaged section.
    4. DNA polymerase: Fills the gap from the primer.
    5. Ligase: Makes the 5′ to 3′ link.
  3. SOS Repair Systems (Without Error BN)

    Replication systems are replaced by a less demanding (DNA polymerase) that continues even without BN and puts a random sequence of bases. Continues replication despite introducing mutations.