Chapter 6: Mutation

Mutation classification and type

Genetic Mutation
Base substitutions
Base insertions
Base deletion
Base inversion
Chromosomal mutation
Structural change/ chromosome aberration
Alterations of chromosomal number
- aneuploidy
- euploidy/ polyploidy

Mutation

A permanent change in amount, arrangement or structure of DNA of an organism

It can be passed to next generation

It may produce a new trait that can be inherited

Mutant

A mutated gene, alternatively, an organism carrying a gene that has undergone a mutation

Mutagen

An agent that induces changes in DNA includes physical agents that DNA/ chemical that
alters DNA bases or by radiation

Type of Mutation
1. Spontaneous Mutation : mistakes happen spontaneously during DNA
replication
2. Induced Mutation: organism exposed to mutagens /caused by mutagens

Mutation Agent (Mutagen)

1. Physical Agent: ultraviolet ray, ionizing radiation
2. Chemical Agent: mustard gas, nitrous acid, base analogue, formaldehyde,
colchicines

2 main types of mutation

1. Genetic Mutation
2. Chromosomal mutation
i)

Alterations in the structure

ii)

Alterations in the number

Genetic Mutation (point mutation)

A change in the nucleotide base sequence of the DNA within a gene
Also known as point mutation (occurs only on a small point on a chromosome)
It occurs only at a specific locus for a gene
Results in a misreading of the genetic code during the translation phase of protein
synthesis
Usually changes the order of amino acids making up a protein
May or may not affect the function of that protein

4 types of genetic mutation

Base substitution
- one base pair in the nucleotide sequence in a gene is substituted with other different base pair
Base insertions
- addition of 1 or a few base pairs in the nucleotide sequence
Base deletions
- loss of 1 or a few base pairs in the nucleotide sequence
Base inversion
- 2 or more base pair are inverted in the nucleotide sequence

1. Base substitution
1 of the nucleotides is replaced with another nucleotide with different base
Leads to different DNA sequence and will be transcribed into different MRNA
The codon of a particular amino acid will be different
The altered MRNA will be translated into a peptide with different amino acid sequence
CAC - AAG - UAU - CAC - UAA
His

lys

tyr

his

(before mutation)

stop

IF MUTATED
CAC - AAG - UGU - CAC - UAA
His

lys

cys

CAC - AAG - UAG

His

lys

his

(missense mutation)

stop

(nonsense mutation)

stop

Changes in base sequence results in changes of codon (UAU/ UGU)

 3 bases / nucleic acid = 1 codon (coding for 1 amino acid)

Changes in codon : (a) amino acid changes (missense mutation)
(b) changes a codon to stop codon (nonsense mutation)

Sickle Cell Anemia

Missense mutation

Defective red blood cell

Produce abnormal Hb- sickle (s) shape

Hb 4 polypeptide chain (2 and 2)

Encode by different gene

Happens because of substitution mutation

Amino acis valine (val) replaces glutamic acid at a single position in protein (- strained)

Patient suffer from anaemia Hb-S stiff and tend to accumulate in small capillary

Hb is not efficient of transporting oxygen

Frame-shift Mutation
Normal code:

GAG - GUU - CCU - AAA - CCU

glu

DELETION:

pro

lys

pro

GAG - UUC - CUA - AAC - CUA

glu

INSERTION:

val

ser

leu

asn

leu

GAG - GUU - CCU - GAA - ACC

glu

val

pro

glu

thr

Involve insertion / deletion of a base pair or more into the nucleotides sequence of DNA

 Many of these deletions / insertion start in the middle of a codon

Shifting the reading frame by 1 or 2 bases.
Frame shift mutation cause the gene to be read in wrong 3 base group (codon)
From the mutation point, it abrupt the coding sequence of amino acids. Changes in
codons results in changes in amino acids
Different polypeptide is produced
Effect- usually harmful to human
Example: major thalesmis

Base inversion

2 base pairs or more in nucleotide sequence are inverted

Change the codons = changes in amino acids

Usually the effect is minor phenotype abnormality

Chromosomal Mutation
a. Structural change of chromosome

Also known as chromosomal aberration

Abnormalities that occur at chromosome structural due to the changes during meiosis

4 types of chromosome aberration:

Deletion
Inversion
Translocation
Duplication

b. Alterations in chromosomal number

- aneuploidy
- Euploidy (polyploidy)
__________________________________________________________________

1. Deletion
The lost of 1 chromosome segment containing 1 or more gene
Fatal even in a heterozygous condition; miscarriage, die in pregnancy; die during baby
level
Example: cri du chat syndrome
Deletion of part of the short arm of chromosome 5
Symptom : catlike cry, small head, facial abnormalities (wide face, wide distance
between eyes) mentally retarded)

2. Inversion

 A region of chromosome breaks off and rotates through 180 degrees before rejoining the
same chromosome
Genetic material of chromosome does not disappear
This inversion chromosome can direct to the meiosis process
It enhance variation among the offspring
Process that suppresses crossing over

3. Translocation
Involve deletion and insertion
Deletion : a chromosome lose part of its segment
Insertion : a chromosome receives part of other segments
Translocation: involves a regional segment of a chromosome breaking off and rejoining
either the other end of the same chromosome or another non-homologous
Reciprocal translocation will only involve the exchange of genetic material
Results in the unbalance combination of genetic material, because:
Unequal genetic material being exchanged
Unequal length of the segment being exchanged

4. Duplication
A region of chromosome becomes duplicated; an additional set of genes exists.

Aneuploidy
Condition where diploid cell (2n) gain / loss 1 or more chromosome
Disjunction: homologous chromosome separated to opposite pole during meiosis
Non-disjunction: both sets of chromosome pass to same pole of the cell
Half the daughter cells produce have an extra chromosome (n+1) whilst the other half
have a chromosome missing (n-1)
Fusion gametes between chromosome (n+1) and normal chromosome (n) produced
embryo with chromosome (2n+1) : Trisomy (e.g. Downs syndrome)
Fusion gametes between chromosome (n-1) and normal chromosome (n) produced
embryo with chromosome (2n-1) : Monosomy (e.g. Turner syndrome)

Downs syndrome

Involves trisomy of chromosome 21

Have typical facial looks with slanting eyes

Shorter stature

Mentally retarded

Sterile

Prone to diseases, so they have shorter life

Short neck

Aneuploidy
Can involve autosome / sex chromosome
Abnormalities in sex chromosome number
- non-disjunction during spermatogenesis
- non- disjunction during oogenesis
Abnormalities in autosome chromosome

Non- disjunction during spermatogenesis

If non-disjunction during meiosis I and II
- SPERM will have abnormal sex chromosome : XY, XX or YY
ABNORMAL sperm
- klinefelter syndrome (XXY)
- super male syndrome (XYY)

Non- disjunction during oogenesis

If non-disjunction happened, some ovum might not carry any chromosome X, some
others might carry 2 chromosome X.
Abnormal ovum X sperm
e.g. Turner syndrome (X0) : TOMBOY
XXX female (metafemale) superfemale

Klinefelter Syndrome (2n+1, trisomy)

He has 47 chromosome with an X chromosome extra (XXY)
STERILE male (small testis), failed to produce sperm
Mentally retarded, short life
Feminized male (soft voice), big breast, long hand and leg
Non disjunction during oogenesis

Turner syndrome, X0 (2n-1, monosomy)

she has 45 chromosome
short stature, sterile female (failed to ovulate)
small breast and undeveloped ovary
dwarf, deaf, abnormal heart and low IQ

XYY syndrome (super male)

non disjunction during meiosis II in spermatogenesis
very aggressive male, above 6 feet tall, generally act and appear normal, produce high
level of testosterone, high tendency to commit crime, usually fertile
during adolescence, they are often slender and have severe facial acne

XXX Female
normal female with mentally retarded, webbed neck
usually long legs, normal development of sexual characteristics

 slight learning difficulties and usually in lower range of normal intelligence

ABNORMALITIES IN AUTOSOME NUMBER

Non-disjunction could also happen to autosome

Example: downs syndrome non disjunction of chromosome 21 during
gametogenesis
Individual with 47 chromosome (instead of 46) appearance of 3
chromosome 21

EUPLOIDY/ POLYPLOIDY
Changes of chromosome number which involves the whole chromosome set (genome)
Number of sets of chromosome exceeds the diploid number by a multiple of n
Occurred when a set of chromosome did not separate during gametogenesis
It happens due to failure of spindle fibers in mitosis or meiosis to segregate chromosomes
into separate group
Common in plants than animals