18.1 Mutations Are Inherited Alterations in the DNA Sequence

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18.1 Mutations Are Inherited Alterations in the
DNA Sequence
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The Importance of Mutations

• Source of all genetic variation, which further
  provides the raw material for evolution
• Source of many diseases and disorders
• Useful for probing fundamental biological
  processes

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Categories of Mutations

• Somatic mutations-occur in body of organism.
  Result in mosaic pattern of cells, but not passed
  down.
• Germ-line mutations-occur in cells producing
  gametes. Mutation is typically passed to half of
  offspring.

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Types of Gene Mutations (based on their molecular
nature)

• Base substitutions
• Transition-Pu for Pu Py for Py
• Transversion-Pu for Py Py for Pu
• Insertions and deletions
• Frameshift mutations-disrupts codon pattern
• In-frame insertions and deletions-insert or
  delete number of bases that is divisible by 3.

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Concept Check 1
Which of the following changes is a transition
base substitution?

1. Adenine is replaced by thymine.
2. Cytosine is replaced by adenine.
3. Guanine is replaced by adenine.
4. Three nucleotide pairs are inserted into DNA.

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Concept Check 1
Which of the following changes is a transition
base substitution?

1. Adenine is replaced by thymine.
2. Cytosine is replaced by adenine.
3. Guanine is replaced by adenine.
4. Three nucleotide pairs are inserted into DNA.

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Phenotypic Effects of Mutations

• Forward mutation wild type ? mutant type
• Reverse mutation mutant type ? wild type
• Missense mutation-results in a different amino
  acid at one position of encoded protein

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Phenotypic Effects of Mutations

• Silent mutation-different codon but still encodes
  for same amino acid
• Neutral mutation-missense mutation that changes
  amino acid sequence, but does not alter function
  of protein
• Nonsense mutation-changes amino acid into stop
  thus producing truncated protein

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Phenotypic Effects of Mutations

• Loss-of-function mutations-cause complete or
  partial loss of protein function
• Gain-of-function mutations-cause either new
  function or function expressed at new times or
  location within organism
• Conditional mutation-altered function only under
  certain conditions (temperature sensitive)

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Phenotypic Effects of Mutations

• Lethal mutation-severe enough to cause premature
  death
• Suppressor mutation a mutation that hides or
  suppresses the effect of another mutation
• Intragenic-mutation in same gene as original
  mutation restores function
• Intergenic-mutation in other gene restores
  function (sometimes in tRNA genes)

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Phenotypic Effects of Mutations

• Mutation rate-the rate at which a mutations
  occur.
• May be determined under normal conditions
• May be determined under altered conditions
• May be determined in the presence of harmful
  chemicals

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Spontaneous Replication Errors

• Caused by mispairing through wobble

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Spontaneous Replication Errors

• Strand slippage

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Spontaneous Replication Errors

• Unequal crossing over

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Spontaneous Chemical Changes

• Depurination loss of purine
• Deamination loss of an amino group

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Chemically Induced Mutations

• Mutagen-a compound that induces mutations
• Base analogs-modified bases that function similar
  to regular bases in base pairing events

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Chemically Induced Mutations

• Alkylating agents donate alkyl group
• Ehtylmethylsulfonate EMS
• Mustard gas
• Deamination nitrous acid

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Chemically Induced Mutations

• Hydroxylamine add hydroxyl group
• Oxidative reaction superoxide radicals
• Hydrogen peroxide
• Intercalating agents proflavin, acridine orange,
  and ethidium bromide

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Concept Check 2
Base analogs are mutagenic because of which
characteristic?

1. They produce changes in DNA polymerase that cause
   it to malfunction.
2. They distort the structure of DNA.
3. They are similar in structure to the normal
   bases.
4. They chemically modify the normal bases.

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Concept Check 2
Base analogs are mutagenic because of which
characteristic?

1. They produce changes in DNA polymerase that cause
   it to malfunction.
2. They distort the structure of DNA.
3. They are similar in structure to the normal
   bases.
4. They chemically modify the normal bases.

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Radiation

• Pyrimidine dimer two thymine bases block
  replication.
• SOS system in bacteria SOS system allows
  bacteria cells to by pass the replication block
  with a mutation-prone pathway.

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18.3 Mutations Are the Focus of Intense Study by
Geneticists
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The Analysis of Reverse Mutations

• Ames Test

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18.4 A Number of Pathways Repair Changes in DNA
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Mismatch Repair

• Mismatch-repair enzyme complex
• Direct repair photolyase

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Mismatch Repair

• Base-excision repair

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Mismatch Repair

• Nucleotide-excision repair

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Mismatch Repair

• Genetic diseases and faulty DNA repair
• Xeroderma pigmentosum

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Concept Check 3
Mismatch repair in bacteria distinguishes between
old and new strands of DNA on the basis of
__________.

1. differences in base composition of the two
   strands
2. modification of histone proteins
3. base analogs on the new strand
4. methyl groups on the old strand

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Concept Check 3
Mismatch repair in bacteria distinguishes between
old and new strands of DNA on the basis of
__________.

1. differences in base composition of the two
   strands
2. modification of histone proteins
3. base analogs on the new strand
4. methyl groups on the old strand