Point Mutations

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Chapter 17

• Lecture 6
• Point Mutations

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Mutations Overview

• Large Scale Mutations
• We discussed these in Chapter 15
• They can alter chromosome structure
• Examples
• Deletions, duplications, inversions,
  translocations, etc. (see page 272)
• Point Mutations
• These are very small changes when compared with
  the large scale mutations just mentioned.
• A point mutation is a change in one or a few base
  pairs in a gene.
• Point Mutations can be divided into two general
  categories
• 1. Base-Pair Substitutions
• 2. Base-Pair Insertions or Deletions

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Base-Pair Substitutions

• A base-pair substitution is the replacement of
  one nucleotide and its partner in the
  complementary DNA strand with another pair of
  nucleotides. Three different results are
  possible
• 1. Silent Mutation
• 2. Missense Mutation
• 3. Nonsense Mutation

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Base-Pair Substitution Silent Mutation

• A silent mutation is one in which a change in one
  base-pair has no effect on the protein produced
  by the gene.
• What do you think accounts for this?
• Redundancy in the genetic code!
• In the following example, both GGC and GGU code
  for the amino acid glycine so the mutation is
  silent, i.e. it never manifests itself in the
  final protein product.

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Base-Pair Substitution Missense Mutation (pt 1)

• A missense mutation is one in which one base-pair
  causes a single amino acid to be changed in the
  resulting protein.
• This mutation is called missense since the code
  is now different.
• In the following example, GGC has been changed to
  AGC resulting in a different amino acid.

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Base-Pair Substitution Missense Mutation (pt 2)

• The effect of a missense mutation on the protein
  is unpredictable.
• A missense mutation is the cause of the disease,
  sickle cell anemia.
• The effects of a change in one base-pair alters
  one amino acid in the resulting hemoglobin
  protein causing red blood cells to take on a
  strange shape.

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Base-Pair Substitution Missense Mutation (pt 3)

• The results of the strange shaped red blood cells
  results in a variety of phenotypic effects in the
  individual.
• Do you remember what is it called when one gene
  causes multiple phenotypic effects?
• Pleiotropy
• Please Note A missense mutation is not always
  bad. It could create a protein that improves
  reproductive success or survivability. Natural
  selection could then help increase the frequency
  of this new allele in the population.

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Base-Pair Substitution Nonsense Mutation

• A nonsense mutation is one in which a change in a
  single base-pair creates a stop codon.
• Because this kind of mutation creates a stop
  signal in the middle of a normally functional
  gene the resulting protein is almost always
  non-functional, and hence the term nonsense
  mutation.

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Base-Pair Insertions and Deletions Frameshift
Mutations

• Insertions and deletions are additions or losses
  of one or more nucleotide pairs in a gene.
• As you might imagine, these kinds of mutations
  have a more disasterous effect on the resulting
  protein than substitutions do.
• Because the genetic code is read as a triplet, an
  insertion or deletion in the nucleotide bases
  that are not multiples of three can cause a
  shift in the reading frame.
• Insertions and deletions are therefore called
  frameshift mutations because everything
  downstream from the mutation will be improperly
  grouped into codons.
• This can result in an entirely new set of amino
  acids (extensive missense) or premature
  termination (nonsense).

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Frameshift MutationsCausing Extensive Missense
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Frameshift MutationsCausing Immediate Nonsense
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Frameshift MutationsInsertion or Deletion of 3
Nucleotides

• If the Insertion or deletion is a multiple of
  three then there may be only a change as little
  as one amino acid and therefore not much
  frameshift.
• The resulting protein can therefore be relatively
  functional depending on the location of the amino
  acid in the protein.

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What Causes Mutations?

• 1. High Energy electromagnetic radiation
• a. Ultra-violet radiation
• It is a good idea to protect yourself from the
  sun.
• b. X-rays
• 2.Mutagenic Chemicals
• The way we can tell if chemicals are mutagenic is
  by using the Ames test.
• Named for Bruce Ames who developed the test at UC
  Berkeley back in the 1970s