MUTATION

• Mutation:

damage to genetic material

or
Changes in DNA that affect genetic
information
 Mutations causes
• There are two ways in which DNA can
become mutated:
– Mutations can be inherited.
• Parent to child
– Mutations can be acquired.
• Environmental damage
• Mistakes when DNA is copied
• A mutation to genetic material is usually not
beneficial. Mutagens are things that cause
mutations, they include:
• 1. High Temperatures
• 2. Toxic Chemicals (pesticides, etc)
• 3. Radiation (nuclear and solar)
 Somatic vs Germ Mutations
New mutations occur in:
• somatic cells
(not inherited but particularly important for
tumour origin, mutations in the skin cells or hair. )
• or the germline
Germ mutations occur only in the sex cells. These
mutations are more threatening because they
can be passed to offspring (forever).
• Mutations effect protein synthesis

• Transcription: Mutated DNA will produce

faulty mRNA leading to the production of a
bad protein.
 Types of mutations

• Chromosomal: affecting whole or a part of a chromosome . Large-

scale chromosome abnormalities, with loss or gain of
chromosomes, breakage and rejoining e.g. deletions, duplications,
inversions, translocations

• Gene: changes to the bases in the DNA of one gene.

Smaller-scale mutations in the structure of a coding gene sequence
or the non-coding DNA. Often milder effect.
Gene Mutations: DNA base alterations
Point Mutations – changes in one or a few nucleotides.
only affect a small part of the gene.
Changes in the third base of a codon often have no effect

• Substitution
• Insertion
• Deletion
• Inversion
• Frame Shifts
 NORMAL PROCESS

DNA (antisense strand) Normal gene

GGTCTCCTCACGCCA
↓
mRNA CCAGAGGAGUGCGGU
Codons
↓
Polypeptide Pro-Glu-Glu-Cys-Gly
Amino acids
Gene Mutations: DNA base alterations
• Substitution- when a base is replaced with a
different base.
CGG CCC AAT to CGG CGC AAT
Guanine for Cytosine
• Insertion - when a base is added
CGG CCC AAT to CGG CGC CAA T
Guanine is added
• Deletion - the loss of a base
CGG CCC AAT to CGG CCA A T
loss of Cytosine
Gene Mutations: DNA base alterations
No change
Normal gene Substitution mutation
GGTCTCCTCACGCCA GGTCTTCTCACGCCA
↓ ↓
CCAGAGGAGUGCGGU CCAGAAGAGUGCGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Glu-Glu-Cys-Gly
Amino acids
Gene Mutations: DNA base alterations
Disaster
Normal gene Substitution mutation
GGTCTCCTCACGCCA GGTCTCCTCACTCCA
↓ ↓
CCAGAGGAGUGCGGU CCAGAAGAGUGAGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Glu-Glu-STOP
Amino acids
Gene Mutations: DNA base alterations
Frame Shift mutations

• A frame shift mutation results from a base deletion or

insertion. Each of these changes the triplets that follow
the mutation.

CGG CCC AAT to CGG CGC CAA T

• Frame shift mutations have greater effects than a point

mutation because they involve more triplets (recall
how important triplets are to protein synthesis)
Gene Mutations: DNA base alterations
• The Frame shift changes the mRNA produced.
• mRNA from DNA as expected……..
GGG CCC TTT AAA to CCC GGG AAA UUU

• Mutated DNA
GGC GCC CTT TAA A to CCG CGG GAA AUU U

• All the triplets are changed, this in turn changes the

amino acids of the protein!
Gene Mutations: DNA base alterations
• Protein shape determines how a protein will
function. A change in one amino acid may
change the shape enough to distort the
protein (as in sickle cell disease). Thus, change
in one base could potentially distort a whole
protein. It is more likely that a frame shift
mutation will change several triplets and
distort a protein’s structure.
Gene Mutations: DNA base alterations
Sickle Cell Anemia
• Discover in 1910 in severely anemic black
youth (9% among black people, every 1 in 70-
300 population)
• Occurred only during low PO2
• Genetically inherited, recessive and autosomal
dominant
sickle crisis with 5000ft flight
Gene Mutations: DNA base alterations
Sickle Cell Anemia
 Electrophoretogram
+
Hb F
Hb A
Hb S

_ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _
- N SD Prone to SD
Gene Mutations: DNA base alterations
Sickle Cell Anemia
• Protein Analysis:
Hb A Val-His-Leu-Thr-Pro-Glu-Glu-Lis
Hb S Val-His-Leu-Thr-Pro-Val-Glu-Lis

• Changing at the 6th amino acid β chain

creating polymers, linear, jelly Hb
sickling cell

cell clotted, plugging small vessels

 Chromosome Mutations
• Changes in number and structure of entire
chromosomes
• Original Chromosome ABC * DEF
• Deletion AC * DEF
• Duplication ABBC * DEF
• Inversion AED * CBF
• Translocation ABC * JKL
GHI * DEF
 Chromosome Mutations
• Down Syndrome
– Chromosome 21 does not
separate correctly.
– They have 47 chromosomes
in stead of 46.
– Children with Down
Syndrome develop slower,
may have heart and
stomach illnesses and vary
greatly in their degree of
inteligence.
 HUMAN GULO GENE MUTATION
• Vitamin C was first isolated in 1928, and in it was
proved to be the agent which prevents scurvy. In
1937 Albert Szent-Gyorgyi was awarded the
Nobel price in medicine for this feat.
• all animals and plants synthesize their own
vitamin C, except for humans and a small number
of other animals, including, apes, guinea pigs, the
red-vented bulbul, a fruit-eating bat and a species
of trout
 HUMAN GULO GENE MUTATION
• mutation in a portion of the human Gulo (L-
gulono-gamma-lactone oxidase) pseudogene
results in lack of ability to synthesise ascorbic
acid
HUMAN GULO GENE MUTATION

• Lots of mutations in the amino acid-

coding regions of the human sequence;
over the span of 54 aas, -18 conserved
amino acid,
-27 non-synonymous substitutions - -7
synonymous changes; many of which
led to nonconservative amino acid
changes.
-2 stop codons (observed as dashes) in
the sequence.
• It is very likely that the accumulation of
random mutations in the gene for the
relevant enzyme has led to massive
changes and destroyed the functional
capacity of the enzyme.
 HUMAN GULO GENE MUTATION
• Nikishima et al (1988): restated the fact that the sequences
in human genomes may represent the remnants of the
gene for the enzyme that was once active but became
nonfunctional during the course of evolution. They isolated
a cDNA encoding L-gulono-gamma-lactone oxidase of the
rat then used this cDNA as a probe for hybridization. The
results confirmed existence of a human DNA sequence
related to this enzyme.
• The nature cause of the mutation in this gene, as stated by
Nikishima et al (1976) is because unadequate dietary intake
of ascorbic acid among these animals. And since the
enzyme is not highly required in the particular
environment, the constraint of selection is removed
 HUMAN GULO GENE MUTATION
• In the Eskimos case, because their main food
are raw meat and fish, which contain high
source of vitamin C, their GULO enzyme is
remain highly required in their ordinary life.
The natural selection did not perform any
changing on this enzyme biological function
because during their evolutionary course of
life, they highly required the capacity to
synthesize ascorbic acid.