Chapter 18 & 8

• Gene mutations & transposons

  
• Ethics paper due Monday, April 1
• Lab report 1 due April 12
• Homework re-dos


  1. I graded each question right / wrong

  2. The answer key is posted

  3. You can go into Gradescope and use the regrade request to explain to me for each question you originally got wrong and would like points for: "Before I thought ___________, now I think ___________"

  4. Your answer must make clear to me what thinking led you to get a wrong answer, and make clear that you now understand how to get the right answer!
• Learning objectives


  • Outline the different ways that gene mutations may arise
  • Explain how mutations have been detected and studied
  • Describe the features and effects of transposable elements

  
• Types & effects of mutations

  • Causes of mutations
  • Studying mutations
  • Types & effects of transposons

  
• Gene mutations


  • Nucleotide tautomers
  • Nonstandard base pairing
  • Strand slippage (insertions/deletions)
  • Unequal crossing over
  • Depurination
  • Deamination

  
• Tautomers


  Molecules may take on more than one arrangement of atoms
• Tautomers


  May cause base substitutions
• Tautomers


  Usually cause A::T -> A::C transitions (pyrimidine -> pyrimidine)

  
• Depurination


  Purines are vulnerable to spontaneous loss
• Deamination


  Removal of the amine group from cytosine converts it into uracil

  
• Causes of spontaneous mutations

  • Nucleotide tautomers
  • Nonstandard base pairing
  • Strand slippage
  • Unequal crossing over
  • Depurination
  • Deamination

  
• Induced mutations


  • Base analogs
  • DNA modifying agents
  • Intercalating agents
• Base analogs


  Structurally similar to normal bases, mistakes occur when incorporated into growing polynucleotide chain
• DNA modifying agents


  Alter a base causing it to mispair
• Intercalating agents


  Distort DNA to induce single nucleotide pair insertions and deletions

  
• Mutagen effects


  • Increase normal mutation frequency
  • Cause point mutations
  • Cause frameshift mutations
  • Cause translocations and rearrangements

  
• Types of chromosome mutations

  • Chromosome rearrangement
  • Aneuploidy
  • Polyploidy

  
• Mutation rate


  Frequency with which a wild type sequence at a locus changes into a mutant allele

  
• Factors affecting measurable mutation rate

  • Frequency of changes in DNA
  • Probability of repair of an alteration in DNA
  • Probability of detection

  
• Mutation rate is usually expressed as # of mutations / biological unit

  
• Ames test


  1. Bacterial strain with a mutation in a histidine synthesis gene

  2. Mammalian liver enzymes

  3. Your suspected mutagen

  
• Ames test


  Tests whether something might be a mutagen - an environmental agent that significantly increases the rate of mutation above the spontaneous rate

  
• Positive Ames test = chemical is a mutagen in bacteria
• Negative Ames test does not mean a chemical is not a carcinogen
• Forward genetics


  Observe a (mutant) phenotype, then look for the mutation that causes it

  
• Reverse genetics


  Make a mutation in a gene of interest, and look to see what the phenotype is

  
• About 45% of our DNA appears to be left-over transposon sequences
• Transposons


  Mobile DNA elements that can move around the genome
• Barbara McClintock's findings on transposons in corn were not initially accepted, but she was awarded the Nobel Prize in 1983
• Types of transposons


  • DNA transposons (class II) - Direct DNA transposition
  • Retrotransposons (class I) - DNA -> RNA -> DNA
• Types of transposition


  • Replicative transposition (copy/paste)
  • Non-replicative transposition (cut/paste)
• Transposon insertion


  Can disrupt gene expression and cause mutation
• Transposons


  Can increase risk of chromosome rearrangements through creating repeat sequences

  
• Hybrid dysgenesis


  Sudden appearance of numerous mutations, chromosome mutations, and sterility in hybrid offspring between two populations

  
• 45% of the human genome is derived from transposable elements
• Alu is the most common transposable element in humans with > 1 million related copies
• Transposable elements have been domesticated and aided in the evolution of the placenta in mammals