ch 15

• Variation in Protein Structure Provides the Basis of Biological Diversity
• Amino acids


  All have a carboxyl group, an amino group, and an R (radical) group bound to a central carbon atom. The R group confers specific chemical properties.
• Types of amino acids

  • Nonpolar (hydrophobic)
  • Polar (hydrophilic)
  • Positively charged
  • Negatively charged
  • Aromatic
  • Contains S
  • Imino acid
  • R is a hydrogen
• Peptide bond


  Covalent bond between the carboxyl group of one amino acid and the amino group of another, formed by a dehydration (condensation) reaction.
• Polypeptide polarity


  Amino (N-) and carboxyl (C-) ends
• Determining polypeptide chain sequence from mRNA sequence

  Read the mRNA sequence 5' to 3' and translate each codon to the corresponding amino acid
• Levels of protein structure

  • Primary: Sequence of amino acids
  • Secondary: α-helix and β-pleated sheets
  • Tertiary: Three-dimensional conformation
  • Quaternary: Composed of more than one polypeptide chains
• Secondary protein structures


  • α-helix and β-pleated sheets
• Tertiary protein structure


  • Stabilized by covalent disulfide bonds, hydrophilic/hydrophobic interactions, ionic bonds, and van der Waals interactions
• Quaternary protein structure


  • Multi-subunits, each subunit is a separate polypeptide with conformations that facilitate their fitting together
• Diverse functions of proteins

  • Enzymes: Catalyze chemical reactions and increase the rate of reactions
• Gene Mutations Are Classified in Various Ways
• Mutations Occur Spontaneously and Randomly
• Spontaneous Mutations Arise from Replication Errors and Base Modifications
• Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation
• Organisms Use DNA Repair Systems to Counteract Mutations
• Mutation


  An alteration in DNA sequence, including base-pair changes, deletions, insertions, and major chromosomal alterations
• Mutations classified by effect on protein sequence

  • Silent: Alters codon but does not change amino acid
  • Missense: Changes codon resulting in altered amino acid
  • Nonsense: Changes codon to a stop codon, resulting in premature termination
• Mutations classified by molecular change

  • Transitions: Pyrimidine replaces pyrimidine, or purine replaces purine
  • Transversions: Purine and pyrimidine are interchanged
• Frameshift mutation


  Insertion or deletion of a base pair that shifts the reading frame during translation
• Mutations classified by phenotype

  • Loss-of-function: Reduces/eliminates function of gene product
  • Null: Results in complete loss of function
  • Dominant: Results in mutant phenotype in diploid organism
  • Dominant gain-of-function: Results in gene with enhanced, negative, or new function
  • Lethal: Interrupt essential processes and result in death
  • Lethal conditional: Dependent on organism's environment
  • Neutral: Effect on genetic fitness is neither beneficial nor detrimental
• Mutations classified by location in a tissue

  • Somatic: Occur in any cell except germ cells, not heritable
  • Germ-line: Occur in gametes, are inherited
• Mutations classified by location on a chromosome

  • Autosomal: Occur within genes located on autosomes
  • X- and Y-linked: Occur within genes located on X and Y chromosomes, respectively
• Spontaneous mutation


  Changes in nucleotide sequence that occur naturally, arising from normal biological or chemical processes that alter nitrogenous bases
• How spontaneous mutations arise

  1. Replication errors: DNA polymerase occasionally inserts incorrect nucleotides

  2. Replication slippage: Loops in template strand cause small insertions and deletions

  3. Tautomeric shifts: Changes in bonding structure allow non-complementary base pairing

  4. Depurination: Loss of purine bases, leading to apurinic sites

  5. Deamination: Conversion of cytosine to uracil, and adenine to hypoxanthine
• If a DNA polymerase encounters an apurinic site during replication


  It will likely insert the wrong nucleotide, leading to a mutation
• Deamination


  The amino group in cytosine or adenine is spontaneously converted to uracil or hypoxanthine, respectively
• Oxidative damage can cause both spontaneous and induced mutations
• Tautomeric shift


  Change in the bonding structure, allowing noncomplementary base pairing
• Transition


  A mutation where one purine is replaced by another purine (A->G, G->A) or one pyrimidine is replaced by another pyrimidine (C->T, T->C)
• Transversion


  A mutation where a purine is replaced by a pyrimidine or vice versa (A->C, A->T, G->C, G->T)
• Tautomeric Shifts May Cause Replication Errors

  Mispairing due to tautomeric shifts may lead to permanent base-pair changes and mutations
• Depurination


  Loss of nitrogenous bases (usually a purine—guanine or adenine), leading to an apurinic site (without purine)
• Deamination


  Amino group in cytosine or adenine is spontaneously converted to uracil, and adenine converted to hypoxanthine
• Deamination results in uracil or hypoxanthine, unnatural bases for DNA!
• Enzyme that catalyzes deamination in RNA

  Adenosine deaminase
• Deamination of cytosine


  Base pair change from C-G to U-G after replication
• Oxidative Damage: Both Spontaneous and Induced Mutations

  • Base modifications
  • Loss of bases
  • Single-stranded and double-stranded breaks
• Transposable Genetic Elements


  DNA elements that move within or between genomes, can act as naturally occurring mutagens, cause inversions, translocations, double-stranded breaks—creates chromosomal damage
• Mutagen types


  • Natural and synthetic chemicals
  • UV light
  • Radiation