3. Definitions
• Mutation = an inherited change in the
genetic material of an organism.
• Mutagens vs. teratogens
• Germline vs. somatic mutation
• Spontaneous vs. induced mutations
4. Types of Mutations
• Most common – base-pair substitutions
– Transition mutations – Pu to Pu, Py to Py.
• GA & A G
• T C & C T
– Transversion mutations – Pu to Py or Py to Pu.
• A T, A C, G T, or G C.
• T A, T G, C A, or C G.
5. Types of Mutations
• Neutral mutations result when amino acid
substitutions do not change protein
function.
• Similar amino acids can be substituted for
each other – isoleucine for leucine.
• Missense mutations result when the amino
acid substitution changes protein function.
– Temperature sensitivity often is a missense
mutation.
6. Types of Mutations
• Nonsense mutations – change in codon to
UGA, UAA, or UAG.
• This results in premature stopping of
protein synthesis.
• They can be lethal or severe in phenotype.
7. Types of Mutations
• The 2nd most common type of mutations are
insertion/deletions of base pairs.
• This can cause frameshifts.
• Deletions or insertions of one or two bases
usually results in dramatic differences in
protein production.
8. Types of Mutations
• Why are these mutations important?
– They can affect mRNA and protein production,
eventually determining the phenotype.
• Silent mutations – produce no change in
amino acid sequence (due to degeneracy of
the genetic code.) (aka synonymous
mutations).
– CUU codes for leucine, but so does CUC, CUA,
CUG, UUA, and UUG.
9.
10. A single base pair mutation in the b-globin gene
changes one amino acid in the coded protein
11. A base pair addition/deletion (frameshift) mutation
results in multiple amino acid changes
downstream from the point of mutation
12. Types of DNA Replication Errors
• Tautomeric shifts lead to mismatched
bases.
• DNA slippage – runs of the same base, or
repeated sequences.
• Depurination and deamination
13. The inheritance of the fragile-X syndrome
(caused by expansion of triplet repeats CGG)
With each passing generation, the number of triplets increases. Once
a threshold number of repeats is reached, the disease phenotype
becomes visible. In this pedigree, such a value is reached in
generation 3.
14.
15. Triplet repeat mutations are created by
template slippage during DNA replication
followed by mismatch repair
16. Part of a messenger DNA containing a G quartet
17. Insertion of a transposon creates short direct repeats
in the target DNA flanking the inserted transposon
26. 5-methylcytosines are hot
spots of mutation-2
Deamination of
cytosine leads to
uracil
while deamination
of 5-methyl-
cytosine leads to
thymine
Uracil is not a
normal
component of
DNA and can be
recognized and
removed.
Thymine is a
normal
component of
DNA and is not
recognized as a
source of potential
mutation.
28. Mechanism of mutagenesis by the tautomerization
of the thymine analog 5-Bromouracil
The keto and enol
forms of DNA
bases
are called
tautomers. Both
thymine and
5-bromouracil can
assume these 2
alternative states.
39. Steps in the excision repair of an
apurinic or apyrimidinic (AP) site
40. Repair of a bubble created in DNA
by the addition of a bulky agent
There is a mistake in this
diagram. The damaged
segment is displaced by a
DNA helicase (not a DNA
polymerase). During the
displacement of a strand by
a DNA polymerase, DNA
synthesis is concerted with
strand displacement and no
gap is formed.
41. Repair of a damage site by recombinational repair
Recombinational
repair is used
when excision
repair fails
42. Restoration of the wild type phenotype by a second
mutation compensating for the first mutation
A mutation that
rescues another
mutation is called
a suppressor
mutation
43. The Ames test for the detection of a
chemical mutagen
Most chemicals that
act as mutagens in
bacteria cause
cancer in animals
