Ch. 16 Genetic variation

• Mutations


  Stable, heritable changes in the sequence of bases in DNA
• Point mutations


  • Most common type of mutation, result from alteration of single pairs of nucleotides or from the addition or deletion of nucleotide pairs
• Larger mutations

  • Insertions
  • Deletions
  • Inversions
  • Duplication
  • Translocations of nucleotide sequences
• Mutations can be

  Spontaneous or induced
• Spontaneous Mutations

  1. Arise without exposure to external agents

  2. May result from errors in DNA replication or the action of mobile genetic elements such as transposons
• Induced Mutations


  Caused by agents that directly damage DNA such as base analogs, DNA modifying agents, and intercalating agents
• Effects of Mutations


  Wild type, Forward mutation, Reversion mutation
• Conditional mutations


  Expressed only under certain environmental conditions
• Auxotrophic mutant


  Unable to make an essential macromolecule such as an amino acid or nucleotide
• Mutations in Protein Coding Genes

  Point mutations can affect protein structure in various ways and are named according to their effects on the encoded protein
• Common types of point mutations

  • Silent, Missense, Nonsense, Frameshift mutations
• Mutations in Regulatory Sequences

  Conditional lac operon mutants, mutations in tRNA and rRNA genes
• Mutant Detection and Selection

  Observation of changes in phenotype, Replica plating technique, Use of environmental conditions to select desired mutants
• Carcinogenicity Testing


  Based on the observation that most carcinogens are also mutagens, e.g., Ames test
• DNA Repair


  Proofreading, Mismatch repair, DNA methylation, Excision repair, Direct repair, errors corrected by DNA polymerase and DNA ligase
• Repair of damage that causes distortions in double helix

  1. Two types of repair systems are known: nucleotide excision repair and base excision repair

  2. Both repair systems remove the damaged portion of the DNA strand and use the intact complementary strand as a template to synthesize new DNA
• Direct Repair

  1. Photoreactivation is used to directly repair thymine dimers

  2. Direct repair of alkylated bases is catalyzed by alkyltransferase or methylguanine methyltransferase
• Recombinational Repair

  1. Repairs DNA with damage in both strands

  2. Involves recombination with an undamaged molecule, often another copy of chromosome is available in rapidly dividing cells

  3. RecA protein catalyzes recombination events
• The SOS Response

  1. Inducible repair system used to repair excessive damage that halts replication

  2. RecA protein initiates recombination repair and acts as a protease, destroying LexA repressor protein

  3. DNA polymerases IV and V synthesize unrepaired DNA in translesion DNA synthesis process
• Creating Additional Genetic Variability

  1. Mutations subject to selective pressure

  2. Recombination is the process in which nucleic acids are rearranged or combined to produce new nucleotide sequences
• Sexual Reproduction and Genetic Variability

  1. Vertical gene transfer is the transfer of genes from parents to progeny

  2. In eukaryotes, sexual reproduction is accompanied by genetic recombination due to crossing over during meiosis and fusion of gametes
• Horizontal Gene Transfer (HGT) in Bacteria and Archaea

  1. HGT differs from vertical gene transfer

  2. Stable recombinant has characteristics of both donor and recipient

  3. HGT is important in the evolution of many species
• More about HGT Mechanisms

  1. Transfer of gene donor to recipient involves Exogenote, Endogenote, Merozygote

  2. Recombination at the Molecular Level: homologous recombination, site-specific recombination, transposition
• Homologous Recombination

  1. Most common type of recombination

  2. RecA proteins carry out the process

  3. Double-strand break occurs between molecules, allowing exchange to be mediated

  4. involves a reciprocal exchange between a pair of DNA molecules with similar nucleotide sequences
• Site-Specific Recombination

  1. Important in insertion of viral genome into host chromosomes

  2. Recombination occurs at specific target sites in DNA molecules, mediated by recombinase enzymes
• Transposable Elements

  1. Segments of DNA that move about the genome in a process called transposition

  2. Simplest transposable elements are insertion sequences

  3. Transposable elements containing 'extra' genes are called composite transposons
• Simple Transposition

  1. Also called cut-and-paste transposition

  2. Transposase catalyzed excision and cleavage of new target site and ligation into site
• Replicative Transposition

  1. Two genes code for enzymes transposase and resolvase

  2. Original transposon remains at parental site in DNA while a copy is inserted in target DNA
• Exogenote


  DNA that is transferred to the recipient
• Endogenote


  genome of recipient 
• Merozygote


  recipient cell that is temporarily diploid as result of transfer process
• DNA Methylation

  Used by E. coli mismatch repair system to distinguish old DNA strands from new DNA strands

  • old DNA (template strand) methylated; new DNA not methylated
  • the repair system cuts out the mismatch from the unmethylated strand
  • Catalyzed by DNA methyltransferases
• Silent mutation


  change nucleoside sequence of codon – but not the encoded amino acid
• Missense mutation

  a single base substitution that changes codon for one amino acid into codon for another amino acid
• Nonsense mutation: converts a sense codon to a stop codon
• Frameshift mutation: results from insertion or deletion of one or two base pairs in the coding region of the gene 
• Reversion mutation: 

  mutant phenotype → wild type phenotype 

  • suppressor mutation: occurs when the second mutation is at a different site than the original mutation
• Forward mutation

  •  wild type → mutant form
• Bacterial Plasmids


  • Small, autonomously replicating DNA molecules
  • Can exist independently from host chromosome
  • Can integrate reversibly into the host chromosome (episomes)
• Conjugative plasmids (F plasmid)


  • Can transfer copies of themselves to other bacteria during conjugation