Mutations
Timothy G. Standish, Ph. D.
©2000 Timothy G. Standish
The Modern Synthesis



Charles Darwin recognized that variation existed in
populations and suggested natural selection as a
mechanism for choosing some variants over others
resulting in survival of the fittest and gradual changes in
populations of organisms.
Without a mechanism for generation of new variation,
populations would be selected into a corner where only
one variation would survive and new species could never
arise.
The Modern Synthesis combines the mechanism of
mutation in DNA to generate variation with natural
selection of individuals in populations to produce new
species.
©2000 Timothy G. Standish
Introduction
The Central Dogma
of Molecular Biology
Cell
DNA
Transcription
Translation
mRNA
Ribosome
Polypeptide
(protein)
©1998 Timothy G. Standish
Mutation
Mutation = Change
 Biologists use the term “mutation” when talking
about any change in the genetic material. Not all
result in a change in phenotype.
 There are two major types of mutations:
 Macromutations - Also called macrolesions and
chromosomal aberations. Involve changes in
large amounts of DNA.
 Micromutations - Commonly called point
mutations and microlesions.

©2000 Timothy G. Standish
Macromutations
 Four
major types of Macromutations are
recognized:
1 Deletions - Loss of chromosome sections
2 Duplications - Duplication of chromosome
sections
3 Inversions - Flipping of parts of
chromosomes
4 Translocations - Movement of one part of
a chromosome to another part
©2000 Timothy G. Standish
Macromutation - Deletion
Chromosome
Centromere
Genes
A
B
C
D
E
F
A
B
C
D
G
H
G
H
E
F
©2000 Timothy G. Standish
Macromutation - Duplication
Chromosome
Centromere
Genes
A
B
C
D
E
F
G
H
A
B
C
D
E
F
EE
FF
G
H
Duplication
©2000 Timothy G. Standish
Macromutation - Inversion
Chromosome
Centromere
Genes
A
B
C
D
E
F
A
B
C
D
F
E
Inversion
G
H
G
H
©2000 Timothy G. Standish
Macromutation - Translocation
Chromosome
Centromere
A
B
C
A
B
E
Genes
D
F
E
C
F
G
H
D
G
H
©2000 Timothy G. Standish
Micro or Point Mutations
Two major types of Macromutations are
recognized:
1 Frame Shift - Loss or addition of one or two
nucleotides
2 Substitutions - Replacement of one nucleotide
by another one. There are a number of different
types:

– Transition - Substitution of one purine for another
purine, or one pyrimidine for another pyrimidine.
– Transversion - Replacement of a purine with a
pyrimidine or vice versa.
©2000 Timothy G. Standish
Frame-Shift Mutations
3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’
5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’
Met
Thr
Cys
Gly
Ser
3’AGTTCAG-TAC-TGA-AAC-CAT-CAA-CTG-ATCATC5’
5’AGUC-AUG-ACU-UUG-GUA-GUU-GAC-UAG-AAA3’
Met
Thr
Leu
Val
Val
Val
Frame-shift mutations tend to have a dramatic effect on proteins
as all codons downstream from the mutation are changed and thus
code for different amino acids. As a result of the frame shift, the
length of the polypeptide may also be changed as a stop codon will
probably come at a different spot than the original stop codon.
©2000 Timothy G. Standish
Substitution Mutations
3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’
5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’
Transition
Met
Thr
Cys
Gly
Ser
3’AGTTCAG-TAC-TGA-ATA-CCA-TCA-ACT-GATCATC5’
5’AGUC-AUG-ACU-UAU-GGU-AGU-UGA-CUAGAAA3’
Met
Thr
Tyr
Gly
Ser
Pyrimidine to
Pyrimidine
3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’
5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’
Transversion
Met
Thr
Cys
Gly
Ser
3’AGTTCAG-TAC-TGA-AAA-CCA-TCA-ACT-GATCATC5’
5’AGUC-AUG-ACU-UUU-GGU-AGU-UGA-CUAGAAA3’
Met
Thr
Phe
Gly
Ser
Purine to
Pyrimidine
©2000 Timothy G. Standish
Transitions Vs Transversions





Cells have many different mechanisms for preventing
mutations
These mechanisms make mutations very uncommon
Even when point mutations occur in the DNA, there
may be no change in the protein coded for
Because of the way these mechanisms work,
transversions are less likely than transitions
Tranversions tend to cause greater change in proteins
than transitions
The Genetic Code
Neutral Non-polar
Polar
Basic
Acidic
F
I U
R
S C
T
†Have amine
groups
*Listed as
non-polar by
some texts
B A
A
S G
E
SECOND
U
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
Phe
Leu
Leu
C
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
AUU
AUC Ile
AUA
AUGMet/start
ACU
ACC
ACA
ACG
GUU
GUC
GUA
GUG
GCU
GCC
GCA
GCG
Val
BASE
A
Ser
UAU
UAC
UAA
UAG
Tyr
Pro
CAU
CAC
CAA
CAG
His
Thr
AAU
AAC
AAA
AAG
Asn†
Ala
GAU
GAC
GAA
GAG
Asp
Stop
Gln†
Lys
Glu
G
UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
Cys
Stop
Trp
U
C
A
G
Arg
U
C
A
G
Ser
Arg
Gly*
U
C
A
G
U
C
A
G
T
H
I
R
D
B
A
S
E
©2000 Timothy G. Standish
The Sickle Cell Anemia Mutation
Normal b-globin DNA
C
Mutant b-globin DNA
T
T
C
G A
A
G U A
mRNA
mRNA
Normal b-globin
Mutant b-globin
Glu
H2 N
C
C
A T
Val
O
OH
H
CH2
H2C
C OH
O Acid
H2 N
C
C
O
OH
H
CH
CH3
H3C
Neutral
Non-polar
Sickle Cell Anemia:
A Pleiotropic Trait
Mutation of base 2 in b globin codon 6 from A to T
causing a change in meaning from Glutamate to Valine
Mutant b globin is produced
Breakdown of
red blood cells
Anemia
Clogging of small
blood vessels
Tower skull
Weakness
Heart failure
Impaired
mental function
Accumulation of sickled
cells in the spleen
Red blood cells sickle
Brain
damage
Paralysis
Pain and
fever
Damage to
other organs
Rheumatism
Kidney
failure
Spleen
damage
Infections
especially
pneumonia
©2000 Timothy G. Standish
©2000 Timothy G. Standish