1. MUTATIONS
Izzati Adilah bt. Azmir
02-039

2. OBJECTIVES
• Learn how the DNA structure can ultimately
change into a new structure and permit a new
phenotypic development.
• Study types of mutation that could be
inherited for the next generation onwards.
• Determine the process and mechanism of
mutation depending on the type of mutagens.

3. LECTURE CONTENT
1. TYPES OF MUTATION AND THE EFFECTS ON
ORGANISM
2. PHENOTYPIC VARIATION
3. FACTORS CAUSING MUTATIONS
4. THE REPAIR OF DNA DAMAGE
5. THE STUDY OF MUTATIONS

4. TYPES OF MUTATIONS
Gene Mutation Chromosome Mutation
• Point Mutation • Deletion
– Silent • Duplication
– Missense
• Inversion
– Nonsense
• Translocation
• Frameshift Mutation
– Addition
– Deletion

5. TYPES OF MUTATIONS
Genome Mutation
• Aneuploidy
• Polyploidy
• Autopolyploidy
• Allopolyploidy

6. GENE MUTATION
Point Mutation
Frame shift

7. GENE MUTATION
• Involve insertion or removal of 1 or more
base pairs
• Gene mutation is a change in single base pair
within DNA sequences

8. EFFECTS OF GENE MUTATIONS
• Most mutations are neutral - they have no
effect on the polypeptide.
• Some mutations result in a less active
product;
• Less often an inactive product;
• Very few mutations are beneficial.

9. EFFECTS OF GENE MUTATIONS(cont)
• Affects molecular changes in the DNA
sequence of a gene
• Alter the coding sequence within a gene
• Causes permanent change in DNA sequence

10. BODY (SOMATIC) AND GAMETE
(GERM)MUTATION
• Body cell mutations can cause cancer.
– only the individual is affected
• Gamete cell mutations affect the egg and the
sperm.
– all offspring of the individual can be affected.
In multicellular organisms (plants or animals) mutations may occur in the somatic cells of the
organism. Somatic cells are the cells involved in growth and repair and maintenance of the
organism. A mutation in these cells may lead to cancer and certain of chromosomal
mutations may be involved in aging. Other mutations happen in the germ cells and these
mutations may appear in the gametes and then in the offspring produced by sexual
reproduction. These sorts of mutations are called germ cell mutations.

11. GENE MUTATION: The Types
1. Point mutations - a one base change in DNA.
2. Frame Shift Mutations - the addition or
deletion of 1 or more bases. These are due to
powerful mutagens; chemical or physical.

12. 1. POINT MUTATION (PM)
3 TYPES:
• silent mutation - single base substitution in the 3rd
base nucleotide position of a codon. This results in NO
change in amino acid. Note that the first 2 letters of
the genetic code are the most critical.
• missense mutation - single base substitution in 1st or
2nd base nucleotide position. This results in changed
amino acid.
• nonsense mutation - single base substitutions that
yield stop codon. Note: there are 3 nonsense codons
in the genetic code = NO PROTEIN

13. PM: Silent mutation
single base
substitution in the 3rd
base nucleotide
position of a codon.
This results in NO
change in amino
acid. Note that the
first 2 letters of the
genetic code are the
most critical.

14. PM: Missense mutation
Single base substitution in 1st or 2nd base nucleotide
position. This results in changed amino acid. This is
equivalent to changing one letter in a sentence, such
as this example, where we change the 'c' in cat to an
'h':
Original : The fat cat ate the wee rat.
Point Mutation : The fat hat ate the wee rat.

16. PM: Nonsense mutation
single base
substitutions that
yield/become stop
codon. Note:
there are 3
nonsense codons
in the genetic
code = NO
PROTEIN

18. 2. FRAME SHIFT MUTATIONS
Gene addition or deletion
One or more bases are added or deleted, the
equivalent of inserting or removing letters in a
sentence. But because our cells read DNA in
three letter "words", adding or removing one
letter changes each subsequent word. This
type of mutation can make the DNA
meaningless and often results in a shortened
protein & non-functional.

19. An example of a frame-shift mutation using our
sample sentence is when the 't' from cat is
removed, but we keep the original letter
spacing:
Original : The fat cat ate the wee rat.
Frame Shift : The fat caa tet hew eer at.

20. 2. FRAME SHIFT MUTATIONS
Additions
Normal gene Addition mutation
GGTCTCCTCACGCCA GGTGCTCCTCACGCCA
↓ ↓
CCAGAGGAGUGCGGU CCACGAGGAGUGCGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Arg-Gly-Val-Arg
Amino acids

21. 2. FRAME SHIFT MUTATIONS
Deletion
Normal gene Deletion mutation
GGTCTCCTCACGCCA GGTC/CCTCACGCCA
↓ ↓
CCAGAGGAGUGCGGU CCAGGGAGUGCGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Gly-Ser-Ala-Val
Amino acids

22. 2. FRAME SHIFT MUTATIONS

23. 2. FRAME
SHIFT
MUTATIONS

25. MUTATIONS CAN BE NEUTRAL
• They may have little or no effect on the survival of
an organism or on its ability to reproduce.
• They may result in the same kind of organism -
meaning that the change still tells the cell to do what
it should, so there is no difference.
• It is estimated that the average human has 50-100
mutations within their DNA - most (if not all) are
neutral or beneficial

26. MUTATIONS CAN BE NEUTRAL (cont)
• Bacterial resistance to antibiotics
• Insecticide resistance in bugs
• Rapid mutation rates in virus’s proteins
allowing them to adapt to new “hosts”

27. MUTATIONS CAN BE BENEFICIAL
• In humans, it can be a different set of
circumstances… Here’s an example:
• Sickle-Cell Anemia is a genetic disorder in which
there is a defect in the structure of red blood
cells. This leads to fatigue and anemia when not
treated.
• However, it has been found that people who are
carriers for Sickle-Cell Anemia also has some
genetic protection against another disease,
malaria.

28. MUTATIONS CAN BE BENEFICIAL
(cont)
• In evolutionary studies, scientists have connected
the presence of a brain chemical microcephalin (a
proposed mutation) with the human’s
development of art, music, and complex tool-
making practices
• This same research indicates that the human
brain is still evolving and becoming more and
more capable of more complex tasks
• Some humans have been found to have
mutations that protect them from other diseases,
such as AIDS

29. CHROMOSOME MUTATION
Deletion
Duplication
Inversion
Translocation

30. CHROMOSOME MUTATION
Chromosome structure become influenced by;
1. Change in amount of genetic information in
chromosome because of
– Deletion
– Duplication
2. Similar amount of genetic information but
the materials are rearranged
– Inversion
– Translocation

31. CHROMOSOME MUTATION (cont)
• Deletion
– Loss of chromosomal segment
• Duplication
– Repetition of chromosomal segment. Gain of segment.
• Inversion
– A change in the direction of the genetic material along a single
chromosome. Reversal of region.
• Translocation
– A segment of one chromosome becomes attached to a different
chromosome
– Simple translocation
• One way transfer
– Reciprocal translocation
• Two way transfer

32. Duplications
• In this mutation, some genes are
duplicated and displayed twice on the
same chromosome. Gain of segment of
DNA.
• Insertion of an extra copy of a region of a
chromosome into a neighboring position.
• Zygotes produced from gametes involving
duplications are often viable and may or
may not have any serious problems.
• Various sorts of duplications are related to
color vision conditions many of which are
quite subtle in their effects e.g certain
anemias involving abnormal
hemoglobins called the thalassemias.

33. Duplications (cont)
• Charcot-Marie-Tooth disease is a group of disorders passed
down through families that affect the nerves outside the
brain and spine. These are called the peripheral nerves.
• Symptoms usually begin between mid-childhood and early
adulthood. They may include:
– Foot deformity (very high arch to feet)
– Foot drop (inability to hold foot horizontal)
– Loss of lower leg muscle, which leads to skinny calves
– Numbness in the foot or leg
– "Slapping" gait (feet hit the floor hard when walking)
– Weakness of the hips, legs, or feet
– Later, similar symptoms may appear in the arms and hands,
which may include a claw-like hand.

34. Duplications (cont)
• Problems in at least 40 genes cause different forms of this disease.

35. Deletions
• Deletions result when a gene is
mistakenly removed from a
chromosome, as a result
of unequal crossing over.
• Often zygotes produced by
gametes involving deletions are
not viable since they do not have
the full compliment of genes.

36. Deletions (cont)
• Cri du Chat results from a very rare mutation caused by the
loss or deletion of a significant portion of the genetic
material from chromosome number five which is vital to
cell growth.
• The cry is caused by an abnormal development of a child’s
larynx

37. Translocation
• Movement of part of a chromosome to
another part of the genome.
• May happen with the same chromosome.
– translocation is an intrachromosome
translocation.
Other translocations involve transfer of a region of a chromosome to a non
homologous chromosome. For example certain types of Down syndrome involve
translocations between chromosome 14 and chromosome 21. This type
of translocation between non homologous chromosomes is called an inter-
chromosomal translocation.

38. Inversion
• Inversions happen when a whole region of
genes on a chromosome gets flipped around .
• 2 types of inversions.
– paracentric inversions the centromere is not
included in the inversion.
– pericentric inversions, the centromere is involved
in the inversion.
Both these types of inversions lead to abnormalities in crossing over and
meiosis resulting in some chromosomes which are not viable, while
others are viable but have new combinations of genes. These sorts
of inversions are thus important in reshuffling genes on a chromosome.

39. TRANSLOCATION INVERSION

40. Inversion (cont)
Inversion mutations, also, only affect a small part of the gene
Normal gene Inversion mutation
GGTCTCCTCACGCCA GGTCCTCTCACGCCA
↓ ↓
CCAGAGGAGUGCGGU CCAGGAGAGUGCGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Gly-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS

41. CHROMOSOME MUTATION

42. Sickle Cell Anemia
• Name of Gene Product: hemoglobin, beta
• Protein Function: Hemoglobin molecules, which
reside in red blood cells, are responsible for carrying
oxygen from the lungs to various parts of the body
for use in respiration.

43. • Sickle-cell anemia is a blood
related disorder that affects the
haemoglobin molecule, and
causes the entire blood cell to
change shape under stressed
conditions.
• In sickle cell anaemia, the
haemoglobin molecule is
defective.
• After haemoglobin molecules
give up their oxygen, some may
cluster together and form long,
rod-like structures which become
stiff and assume sickle shape.

44. Sickle Cell Anemia
Mutation of hemoglobin gene

45. GENOME MUTATION
Aneuploidy
Polyploidy
Autopolyploidy
Allopolyploidy

46. • Normal organism is euploid with exact
chromosome number that is multiple of
chromosome set (2n).
• E.g Drosophila melanogaster normally with 8
chromosome. The species is diploid, having
two sets of 4 chromosomes each.
Rare occasion where abnormal fruit fly produce 12
chromosomes, containing 3 sets of 4 chromosomes each.
This alteration is called triploid fruit fly with 12 chromosomes.
What about triploid individual?

47. Chromosome numbers can vary in 2 ways
Polyploid
– An increase in the number of the complete sets of
chromosome
– In animals and plants
Aneuploid
– Abnormal number of chromosomes within a set
– Variations are less common

48. CHANGES IN CHROMOSOME
NUMBER
a. Aneuploidy
b. Polyploidy
c. Autopolyploidy
d. Allopolyploidy

49. a. Aneuploidy
• Normally 2N (haploid individual) ends up either with extra
copies of homologous chromosomes or fewer than the
normal diploid number.
• Happens when homologous chromosomes fail to segregate
properly during meiosis (non disjunction).
• Monosomy (2n-1) in which the diploid individual has only
one member of a certain homologous chromosome.
• The other common type of aneuploidy is called trisomy
(2n+1) because the individual has three copies of the
particular chromosome.

50. a. Aneuploidy (cont)
• Happens when homologous chromosomes fail
to segregate properly during meiosis (non
disjunction).

51. a. Aneuploidy (cont)
• Aneuploidy leads to a number of syndromes in humans. For
example trisomy 21 leads to Down syndrome,
characterized by mental retardation and other
abnormalities.
• Aneuploidy involving the sex chromosomes is common.
XYY males are normal but…
• XXY males and XXXY males have a syndrome called
Klinefelter syndrome. These males are often actually
intersexed or hermaphroditic with partially developed
sexual organs of both genders. These individuals are sterile
and are often subjected to hormones and surgery to bring
them into conformance with social gender roles.

52. a. Aneuploidy (cont): Klinefelter
syndrome

53. a. Aneuploidy (cont): Klinefelter
syndrome
• As XXY males enter puberty, they often don't make as much
testosterone as other boys.
• Can lead to a taller, less muscular body, less facial and body hair,
and broader hips than other boys.
• As teens, XXY males may have larger breasts, weaker bones, and a
lower energy level than other boys.
• By adulthood, XXY males look similar to males without the
condition, although they are often taller. They are also more likely
than other men to have certain health problems, such
as autoimmune disorders, breast cancer, vein
diseases, osteoporosis, and tooth decay.
• XXY males can have normal sex lives, but they usually make little or
no sperm. Between 95% and 99% of XXY males are infertile because
their bodies don't make a lot of sperm.

54. Edwards
Trisomy 18

55. The ‘XYY’ Jacob’s syndrome men
• 47,XYY ; an extra copy of the Y chromosome
• Taller than average, but typically causes no unusual physical
features. Most have normal sexual development and are able to
father children.
• Associated with the risk of learning disabilities and delayed
development of speech and language skills. Delayed development
of motor skills (such as sitting and walking), weak muscle tone
(hypotonia), hand tremors or other involuntary movements
(motor tics), and behavioral and emotional difficulties are also
possible.
• A small percentage of males with 47,XYY syndrome are diagnosed
with autistic spectrum disorders, which are developmental
conditions that affect communication and social interaction.

56. The ‘XYY’ Jacob’s syndrome men

58. b. Polyploidy
• 3N/sets or more of chromosomes in a nucleus.
• Can happen because of a failure of the spindle fibers in
mitosis or meiosis to segregate chromosomes into
separate groups.
• Many organisms have specialized polyploid tissues
even organisms we typically consider as diploid.
– For example in plants a so called double fertilization leads
to the genesis of a diploid zygote from the union of two
gametes produced by the haploid gametophytes, but also
a specialized triploid tissue (3N) called endosperm. This
tissue is produced when a male gamete fertilizes special
diploid tissue from the flower. In mammals, cells of the
liver are typically polyploid.

59. b. Polyploidy (cont)
• Believed to be an important mechanism in the development of new
species and a common pattern in plants is to find populations of
two species both of which might be diploid. Where the species
overlap a series of localized polyploid populations are often found.
These polyploid populations are often effectively reproductively
isolated from the parent species and thus can be considered
species in their own right.
• E,g plant species and some fish and amphibians;
– domestic wheat is hexaploid(6N). ‘
– Seedless plants are usually triploid (3N).
Consider a tetraploid plant (4N). The gametes of this plant are going to be effectively
diploid (2N) and if they are fertilized by a normal haploid gamete (N), the result is a
triploid plant. Since triploid plants have an odd number of chromosomes, typically the
gametes have variable number of chromosomes are usually not viable. This is why
triploid plants are used to produce seedless plants. Since most plants can self
fertilize, the tetraploid plant can breed with itself and produce viable tetraploid
populations.

60. b. Polyploidy (cont)

61. b. Polyploidy (cont)
• Individuals with triploid syndrome have three of every
chromosome for a total of sixty-nine rather than the
normal forty-six chromosomes.
• Babies with Triploid Syndrome usually are lost through
early miscarriage. However, some infants have been
born and survived as long as five months. Affected
infants are usually small and have multiple birth
defects.
• Those that survive are usually mosaic, meaning that
some cells have the normal number of 46
chromosomes and some cells have a complete extra
set of chromosomes.

62. c. Autopolyploidy
• Autopolyploidy is polyploidy in which all the
chromsomes originate from the same diploid
parent species.
• Domestic banana and various seedless plants
are often triploid autoployploids.

63. d. Allopolypoidy
• Allopolypoidy is a polyploidy in which the sets of
chromosomes are from different species. Usually
hybrid plants (N1 + N2) from such crosses are not
fertile since proper pairing of chromosomes does not
occur in meiosis.
• But sometimes the chromosome number
spontaneously doubles leading to tissues with 2N1 +
2N2. If this tissue is germ tissue, tissue that can give
rise to haploid tissue via meiosis, the result can be
gametes with the N1 + N2 chromosome complement.
• When two of these gametes fuse, the result is an
allopolyploid plant with a viable chromosome
complement (2N1 + 2N2).

65. FACTORS CAUSING MUTATIONS

66. Factors that causes mutation
2 Factors that contribute to mutation
– Error in DNA replication.
– Damaging effects of mutagens
• CHEMICALS: Alkylating agents like nitrosoguanidine,
nitrosamine, etc.
• RADIATIONS: X-rays, U.V.rays, etc.

67. Error in replication

68. Factors that causes mutation
Chemical mutagens - used in research to study mutagenesis. There are 3
kinds of chemical mutagens.
1. Alkylating agents.
– Adds alkyl group, such as methyl group CH3 CnH(2n+1), result in mispairing
bases in DNA replication
– Pairing with wrong bases; methyl group bond with G, it will pair with thymine
instead of cytosine.
– Eg. formalin, nitrogen, mustard, and ethylene oxide (reacts with G changing it
to bind with T).
2. Intercalating agents.
– Inserts into DNA and pushes bases apart.
– Eg. AFLATOXIN - a chemical produced by peanut and grain molds. The mold is
Aspergillus flavus (fungus) causing framshift mutation.
– Eg. Benzopyrene – from smoke causing frameshift mutation.

69. 3. Base analogs.
– Mimics a nitrogenous base. Eg. AZT is a modified
sugar that substitutes for T.
– Eg. 5 - bromouracil binds with A or G.

70. Factors that causes mutation (cont)
Physical mutagens:
1. Nonionizing radiation
– Causes the formation of T= T dimers. UV light @ 260 nm.
– Affecting formation harmful covalent bonds between pyrimidine (T
and C).
– Forming gap in in DNA strand = no pairing, no replication = cell death

71. 2. Ionizing radiation
– damages DNA by causing the formation of “free
radicals” leading to mutations.
– Eg. X-rays. Gamma rays from radioactive fallout
penetrates the body. Alpha rays from inhaled dust
containing radioactive fallout.

72. Possible effects of Mutagens

73. STUDY OF DNA REPAIR
Types of repair:
1. Dimer repair
• Light repair
• Dark Repair
2. Other types
• Methylases

74. Light Repair
• Also known as photoreactivation
• When bacteria that previously exposed to UV
light, they should be later exposed to visible light.
• The visible light will induce the bacteria to
produce an enzyme to repair the mutation.
• Phytolases – light repair enzyme
• Helps in separating the dimers of two thymine
• Using visible energy

75. Light Repair (cont)

76. Dark Repair
• Nucleotide excision
• Repair mutation from any causes including
dimer
• The enzyme will cut off the incorrect bases
and fill it with newly synthesized DNA
• The enzyme occur in either present or absent
of light.

78. Methylases
• Discover by Hamilton Smith, explain how the
abnormal DNA sequences that is not obviously
show the different such as dimer, could be
detected.
• The methylases will bound with all normal
bases that following the parents strands.
• Endonuclease then cut the bases that doesn’t
have the methylases bond.

79. THE STUDY OF MUTATIONS
The fluctuation test
Technique of replica plating

80. Why This Study Was Introduced?
• Problems faced by scientists have led to the
study of mutation – costly and long period.
• Objective of the study are:
– To differentiate between spontaneous mutation
and induced mutation
– To isolate particular mutant from culture that
containing both mutation and normal
microorganism.

81. The Fluctuation Test
• Introduced by Salvador Luria and Max
Delbruck (1943)
– E.g. Penicilin
• The mutation might occur in early culture
naturally or have been induced by its
environment during replication.
• Ames use their idea and invent new test.
• This test is to differentiate.

82. Ames Test

83. The Replica Plating
• Introduced by Joshua and Esther Lederberg
(1952)
• Similar reason as the fluctuation test.
• The particular mix culture m/org was prepared
in master plate.
• A sterile velveteen pad was then gently
pressed on the master plate.
• Then it will be pressed to 2 other plates.

85. Reference
• Replica Plating
http://www.sumanasinc.com/webcontent/anim
ations/content/replicaplating.html