chapter 15

• Mutation


  Change in nucleotide sequence of DNA that can be passed on from a parental cell to daughter cells or from parental organisms to offspring
• Somatic mutations


  • Only occur in somatic cells that will never undergo meiosis (only mitosis)
  • Passed to daughter cells in mitosis
  • Not inherited by sexually produced offspring
• Germ-line mutations


  • Can only occur in stem cells that become gametes, or actual gametes
  • Can be inherited by the next generation of sexually produced offspring
  • For multicellular eukaryotes, these mutations are present in 100% of cells of offspring arising from gametes possessing mutations
• Most amino acids are coded by >1 codon (i.e., the Universal Genetic Code is redundant!)
• Addition


  Inserting new character(s)
• Subtraction


  Deleting existing character(s)
• Substitution


  Overwriting just one character
• Point mutations


  • Consisting of additions or deletions of multiple nucleotides are still small enough to only affect one gene!
• Types of point mutations


  • Addition
  • Subtraction
  • Substitution
• Transition


  Purine stays purine or pyrimidine stays pyrimidine
• Transversion


  Purine becomes pyrimidine or pyrimidine becomes purine
• Point mutations occur at a single nucleotide position in the genome, usually changing just 1 nucleotide base
• Silent mutations


  Do not change a protein's function(s)
• Silent mutations occur in coding DNA regions but do not change a protein's function(s) (e.g., within exons or exon/intron boundaries in protein-coding genes)
• Most often, silent mutations result from base substitutions at the 3rd nucleotide base within codons
• In these cases, protein primary structure (amino acid sequence) is unchanged
• Silent mutations


  Can also occur when coded amino acid changes to a chemically similar alternative (e.g., Leucine (Leu) -> Isoleucine (Ile), Glutamate (Glu) -> Aspartate (Asp))
• If a mutation causes no detectable change in a protein's function(s), then it is silent!
• Silent mutations change a genotype without a change in phenotype
• Loss of function mutation


  • Gene may not be expressed at all
  • Gene may give dysfunctional protein
  • Almost always recessive, wild type makes enough functional protein
• Gain of function mutation


  • Protein has altered function
  • Dominant inheritance usually
  • Wild type does not prevent mutant function
  • Cancer mutation in oncogenes, so stimulate cell division
• Conditional mutations


  • Change phenotypes only when certain conditions are present
  • Changes in variables that control whether proteins fold normally (e.g., temperature, pH, concentrations of essential ions, etc.) drive phenotypic changes seen with most conditional mutations
• Temperature sensitive (ts) conditional mutations


  Are common and very useful when studying essential genes
• Cat example: ts mutations in a protein-coding gene required for black pigmentation of fur


  • Result in black fur only if temperature is low enough to keep the protein stable
  • Skin with low average temperatures -> protein stable -> ears, nose, tail, paws have black fur
  • Skin near body core is warmer -> protein unstable -> body core has light colored fur
• Reversion mutation


  1st mutation happens, then 2nd mutation changes back to original sequence, or sequence that gives non-mutant phenotype
• In coding regions, point mutations as silent mutations change mRNA sequence, may not change amino acids
• Point mutation as missense mutation: base substitution


  Alter genetic code so another amino acid substituted in protein
• Sickle cell affects hemoglobin protein


  • One base pair change from wild type
  • One amino acid different
  • Low oxygen hemoglobin sticks in long strands inside cell
  • Floppy RBC -> sickle celled
• Missense mutations may not affect protein shape/function if similar amino acid is used
• Missense mutation


  Can be gain of function (e.g. P53 mutated in cancer: does not stop cell division as it should)
• Point mutation as nonsense mutation


  Brings up stop codon early, resulting in a shorter protein
• Thalassemia hemoglobin disease


  • Very short, not functional protein
• Frame shift mutations


  Add or delete 1 or 2 nucleotides, altering the reading frame (consecutive codons of mRNA)
• If 3 nucleotides change, it does not shift the entire reading frame downstream
• Frame shift mutations almost always result in nonfunctional proteins
• Mutations outside coding regions may not have phenotypic effect, though still a mutation
• Chromosomal mutations


  • Extensive changes, DNA breaks and rejoins
• Types of chromosomal mutations


  • Chromosome deletion (remove part of DNA)
  • Chromosome duplication (homologous chromosomes break at different positions, then reconnect to wrong piece)
  • Inversion (break & rejoin, rejoined piece runs opposite from original orientation)
  • Translocation (segment of chromosome breaks off, attached to different chromosome)
• For large parts of chromosome 21, translocation may lead to Down syndrome
• Retroviruses insert into host genome randomly, and if inserted within a gene, may cause loss of function