Genetics- Chapter 15 Gene Mutation, DNA Repair, and Transposition

Chapter Overview

  • Chapter Title: Gene Mutation, DNA Repair, and Transposition

  • Edition: Twelfth Edition

  • Copyright: 2021, 2019, 2015 Pearson Education, Inc.

15.1 Gene Mutations Are Classified in Various Ways

  • Mutation Definition: An alteration in the DNA sequence, encompassing:

    • Single base-pair substitutions

    • Deletions or insertions of base pairs

    • Major alterations in chromosomal structure

  • Occurrence: Mutations can occur in:

    • Somatic cells (non-heritable)

    • Germ cells (heritable)

    • Coding or noncoding regions of the genome

Types of Mutations (by Molecular Change)

  • Point Mutation/Base Substitution: Change from one base pair to another.

    • Missense Mutation: New triplet code for a different amino acid.

    • Nonsense Mutation: New triplet code for stop codon, terminating early.

    • Silent Mutation: New triplet code still codes for the same amino acid.

  • Transitions: Purine to purine or pyrimidine to pyrimidine substitutions.

  • Transversions: Purine and pyrimidine interchanged.

Frameshift Mutations

  • Caused by insertions or deletions of base pairs.

  • Alters the reading frame during translation.

    • Example:

      • Original: "THE CAT SAW THE DOG"

      • Frameshift due to deletion: "THE ATS AWT HED OG"

      • Frameshift due to insertion: "THE CMA TSA WTH EDO G"

Phenotypic Classification of Mutations

  • Loss-of-Function Mutations: Reduce or eliminate function of gene product.

    • Null Mutation: Complete loss of function.

  • Gain-of-Function Mutations: Mutant phenotype manifesting novel or excessive activity.

  • Visible (Morphological) Mutations: Observable traits.

  • Nutritional/Behavioral Mutations: Affect metabolic functions or behavioral traits.

  • Regulatory Mutations: Impact gene regulation observed in environmental changes.

  • Lethal Mutations: Result in the death of the organism.

  • Conditional Mutations: Effect depends on environmental condition, e.g., temperature-sensitive mutations.

Location-Based Classification of Mutations

  • Somatic Mutations: Occur in somatic cells; non-heritable.

  • Germ-Line Mutations: Occur in gametes; heritable.

  • X- and Y-Linked Mutations: Mutations located on sex chromosomes.

15.2 Mutations Occur Spontaneously and Randomly

  • Spontaneous Mutations: Natural changes in nucleotide sequences; generally low rates.

  • Induced Mutations: Result from external agents such as:

    • Radiation (e.g., UV, X-rays)

    • Chemicals (natural and synthetic)

15.3 Spontaneous Mutations Arise from Replication Errors and Base Modifications

  • Replication Errors: Imperfect copying by DNA polymerase can lead to point mutations.

  • Replication Slippage: Occurs during replication, especially in repeated sequences, leading to insertions or deletions.

  • Tautomeric Shifts: Causes mispairing during DNA replication due to alternate chemical forms of bases.

  • DNA Base Damage: Depurination (loss of purine bases) and deamination (conversion of cytosine to uracil) can alter base pairing.

  • Oxidative Damage: By-products from cellular processes or radiation can damage DNA leading to mutations.

  • Transposable Elements: DNA segments that can move within the genome and can act as mutagens.

15.4 Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation

Mutagens

  • Natural or artificial agents that induce mutations.

  • Examples include:

    • Fungal toxins

    • UV light

    • Industrial pollutants

    • Medical X-rays

    • Chemicals found in tobacco smoke

Types of Chemical Mutagens

  • Base Analogs: Compounds that can substitute for normal bases, altering base-pairing.

  • Alkylating Agents: Chemicals that add alkyl groups to DNA bases, affecting pair affinity and increasing mutation rates.

  • Intercalating Agents: Chemicals that insert themselves between base pairs, distorting DNA.

  • Adduct-Forming Agents: Bind to DNA, altering conformation, and interfering with replication (e.g., acetaldehyde).

Radiation Effects

  • UV Light: Leads to formation of pyrimidine dimers, distorting DNA structure.

  • Ionizing Radiation: Causes direct DNA damage through ionization of molecules, leading to mutations.

  • Free Radicals: Reactive molecules that can cause significant alterations to DNA.

15.5 Single-Gene Mutations Cause a Wide Range of Human Diseases

  • Monogenic Diseases: Often resulting from a single base-pair mutation; examples include:

    • Missense: Achondroplasia (mutation in FGFR3 gene)

    • Nonsense: Marfan syndrome (mutation in fibrillin-1 gene)

    • Insertion: Familial hypercholesterolemia (varied insertions in LDLR gene)

    • Deletion: Cystic fibrosis (deletion of phenylalanine in CFTR gene)

    • Trinucleotide Repeat Expansions: Huntington disease (CAG repeats in Huntington gene).

15.6 Organisms Use DNA Repair Systems to Counteract Mutations

  • DNA repair systems maintain genetic integrity and counteract damage from both spontaneous and induced mutations.

Repair Mechanisms

  • Proofreading: DNA polymerase reviews and corrects synthesis errors.

  • Mismatch Repair: Clears and repairs mismatched nucleotides post-replication.

  • Excision Repair: Repair mechanism for damage, employing the following:

    • Base Excision Repair (BER): Targets damaged bases.

    • Nucleotide Excision Repair (NER): Handles bulky distortions in DNA.

  • Homologous Recombination Repair: Repairs double-strand breaks using sister chromatids as templates.

  • Nonhomologous End Joining: Ligates broken ends of DNA strands without a template.

15.7 The Ames Test is Used to Assess the Mutagenicity of Compounds

  • Ames Test: Utilizes strains of Salmonella typhimurium to measure the mutagenic potential of compounds.

  • Procedure Summary:

    • Assess frequency of reverse mutations in the presence of test compounds to determine mutagenic effects.

  • Implications: Strong correlation between Ames test results and carcinogenic potential; many known carcinogens test positive.