Chapter 14 - Gene Mutation, DNA Repair, and Transposition

Chapter 14 - Gene Mutation, DNA Repair, and Transposition

14.1 - Gene Mutations Are Classified in Various Ways

  • Types of Mutations

    • Spontaneous mutations

    • Happen naturally and randomly

    • Usually linked to normal biological or chemical processes in the organism

    • Induced mutations

    • Result from the influence of an extraneous factor, either natural or artificial

  • Classification by Type of Inheritance

    • Somatic mutations

    • Occur in any cell except germ cells

    • Not heritable

    • Germ-line mutations

    • Occur in gametes

    • Are inherited

    • Autosomal mutations

    • Occur within genes located on the autosomes

    • X-linked mutations

    • Occur within genes located on the X chromosome

  • Classification by Type of Molecular Change

    • Point mutations

    • Base substitutions where one base pair is altered

    • Transition

      • A pyrimidine replaces a pyrimidine or a purine replaces a purine

    • Transversion

      • A purine and a pyrimidine are interchanged

    • Frameshift mutations

    • Result from insertions or deletions of a base pair (or any number of bases except multiples of 3)

  • Classification by Type of Codon Change

    • Missense mutations

    • Alter a codon, resulting in an altered amino acid within a protein-coding portion of a gene

    • Nonsense mutations

    • Change a codon into a stop codon, resulting in premature termination of translation

    • Silent mutations

    • Alter a codon but do not change the amino acid at that position of the protein

  • Classification by Effect of Mutation

    • Conditional mutations

    • Have effects depending on the environment in which the organism finds itself

    • Lethal mutations

    • Interrupt essential processes, resulting in death

14.3 - Spontaneous Mutations Arise From Replication Errors and Base Modifications

  • Spontaneous Mutations

    • DNA polymerase occasionally inserts incorrect nucleotides due to mispairing

    • Slippage during replication can lead to small insertions or deletions

    • DNA may suffer oxidative damage from by-products of normal cellular processes

    • Integrations of transposons can act as naturally occurring mutagens

  • Tautomeric Shifts

    • Result in mutations due to anomalous base pairing

  • Depurination and Deamination

    • Most common cause of spontaneous mutation

    • Depurination

    • Loss of a purine base from the DNA

    • Deamination

    • Removal of an amine group from a base, which can result in a base change

14.4 - Induced Mutations Arise From DNA Damage Caused by Chemicals and Radiation

  • Mutagens

    • Natural or artificial agents that induce mutations

    • Base analogs

    • Can substitute for purines or pyrimidines during nucleic acid replication

    • Acridine dyes

    • Cause frameshift mutations by intercalating between purines and pyrimidines

    • Ethidium Bromide

    • An example of an acridine dye

  • UV Radiation

    • Creates pyrimidine dimers that distort DNA conformation, resulting in errors during replication

  • Ionizing Radiation

    • Takes the form of X rays, gamma rays, and cosmic rays

    • Induces point mutations and chromosomal aberrations

14.6 - Organisms Use DNA Repair Systems to Counteract Mutations

  • Proofreading

    • During DNA synthesis, bacterial DNA polymerase III inserts the wrong base approximately 1 time per 100,000 insertions, with an error rate of approximately 10^{-5}

    • DNA polymerase III can recognize and correct errors during replication, a process known as proofreading

    • It corrects about 99% of its insertion errors

  • Postreplication Repair

    • Occurs when DNA replication skips over a lesion and requires homologous recombination

  • Nucleotide Excision Repair (NER)

    • Repairs bulky lesions in DNA

    • Involves:

    1. Removal of mutation by a nuclease

    2. Gap filling by DNA polymerase

    3. Sealing of the nick by DNA ligase

14.7 - The Ames Test Is Used to Assess the Mutagenicity of Compounds

  • Ames Test

    • Utilizes strains of Salmonella typhimurium selected for increased sensitivity to mutagens and the ability to reveal specific types of mutations

    • Some chemicals are not mutagenic or carcinogenic in their original form but become converted into mutagens or carcinogens upon metabolic processing

    • The test often includes a mixture of liver enzymes reflecting this metabolic conversion