MUTATION

 Mutation is the change in the genetic constitution of an organism.

 There are two types of mutations:
1. Gene or Point Mutation – change in the NUCLEOTIDE SEQUENCE of a gene.
2. Chromosomal Mutation – change in the NUMBER or STRUCTURE of entire
chromosomes.
 Mutation is heritable when it occurs in gametes.
 Mutation may be spontaneous (naturally occurring) or may be induced (by radioactivity).
 Spontaneous mutations arise when individual bases undergo tautomeric shifts, that is, a
rearrangement of their normal ring structure. Such rearrangements cause pairing between non-
complementary bases.

GENE MUTATIONS
 Involves the alteration of the sequence of bases in a gene.
 Since each gene codes for a specific polypeptide, then any alteration of the gene will result in a
different product (polypeptide).
 The mutated product is usually harmful to the organism but not always.
 Furthermore, a mutation may prevent the formation of any product at all.

TYPES OF GENE MUTATIONS

1. ADDITION- one (or more) nucleotide pair is added to the gene sequence.

2. DELETION- one (or more) nucleotide pair is removed from the gene sequence.

The base pairs may be added or deleted terminally or intragenic. Additions and deletions are FRAME
SHIFT MUTATIONS. The READING FRAME refers to the sequence of codons present in a gene, because
they are read from a specific starting point. Additions and deletions alter the sequence of nucleotides
and thus how the frame reads; hence the term: FRAME SHIFT.
For example- a part of a normal RNA frame reads : AUG CCU GGG UUU AGU CCA AAG
Addition of a G at codon 4 base 3 results in : AUG CCU GGG UUG UAG{stop}

*in this case the rest of the product is lost because a stop codon is formed. Thus the protein
structure will be incomplete.

RESULTS OF FRAME SHIFT MUTATIONS

 Stop codon will be misread resulting in a longer or shorter polypeptide than the normal
product.
 Codon sequence will be altered so protein produced will be defective or unable to function at
all.
 3. SUBSTITUTION- the exchange or replacement of one BASE for/by another. There are two types of
substitutions :
a. Transitions- the replacement of a purine by a purine or pyrimidine by a pyrimidine.
b. Transversions- the replacement of a purine by a pyrimidine or vice versa

Substitution Mutations are NOT frame shift mutations. They still however may radically change the protein
product.

Sickle cell Anaemia is a condition that results from a substitution mutation. The gene sequence is altered
such that the amino acid glutamate is replaced by valine.

DESCRIPTIONS OF POINT MUTATIONS

 MIS-SENSE MUTATION- substitution, addition or deletion that results in the placement of an amino
acid in a position that it should not be in the polypeptide chain. For this to occur a different codon
from the normal would have been formed at the position in question.

 NON-SENSE MUTATION- substitution, addition or deletion that leads to the formation of a stop codon.
The stop codons are: UAA, UAG, UGA. The resulting polypeptide will be too long or short, will not fold
properly, and so will not be able to function properly, if at all.

 SILENT MUTATION- substitutions that are not expressed in the phenotype. For instance, if UAC is
changed to UAU there will be no noticeable effect because both those sequences code for the same
amino acid- tyrosine; and both UGC and UUC code for serine. The product will not be changed.

CHROMOSOMAL MUTATIONS

 Mutations involving the chromosome number or structure. Not just a gene along the chromosome, but
the entire chromosome is affected.
 CHANGE IN CHROMOSOME NUMBER- mutation in which the number of chromosomes is not the
normal for the species in question. There are two types of chromosome number mutations:

1. EUPLOIDY—Mutation in which the number of chromosome sets differ from normal. Organisms
with such mutations are called euploids. For instance humans normally have 23 sets of
chromosomes; each set containing two chromosomes. A euploid individual may have 22 sets of
two instead. NB. This would be fatal from the embryonic stage.

2. ANEUPLOIDY—mutation in which the individual number of chromosomes is not accurate for

that species. Individual chromosomes are missing or present more than once. For instance
humans possess 46 chromosomes normally (23 sets of 2). An aneuploid may have 47
chromosomes; 45; 48 etc.
 EUPLOIDY

PLOIDY refers to the number of times each chromosome set is present in the nucleus of an
organism. If ‘n’ is the number of chromosomes in a set, then
n--- monoploid eg. tobacco
2n—diploid eg. humans, tomato
3n—triploid eg. banana, sugar beets
4n—tetraploid eg. potato, grape
6n—hexaploid eg. wheat
8n—octoploid eg. strawberry
10n-decaploid eg. sugarcane

Polyploidy is when the number of chromosome in a set is more than 2n. There are two types of
polyploidy: AUTOPOLYPLOIDY and ALLOPOLYPLOIDY

AUTOPLOIDY- situation in which the same set(s) of chromosomes of the same species is
increased.
Eg. Where C is a chromosome: CC [diploid] is mutated to CCCC [tetraploid]

ALLOPLOIDY- situation in which the chromosome sets from two different species (hybrid)
increase.
Species 1—CC + Species 2—BB = Hybrid- BC which may mutate to BBCC

Polyploidy is more common in plants than animals. Polyploidy occurs if there is a mistake in
mitosis or meiosis. Polyploidy may be induced by exposing the species to a chemical named
colchicine that inhibits the formation of spindle fibres. In odd number polyploids (3n, 5n, etc),
meiosis is never normal.
Effects of Polyploidy
Chromosome numbers in a cell will increase, which causes an increase in the size of the plant.
We are thus able to achieve increased fruit size, increased flower size and flowers and fruits also
stay fresh longer.

ANEUPLOIDY

Aneuploid organisms either have extra chromosome(s) or are missing chromosome(s).

TYPES OF ANEUPLOIDS
MONOSOMICS : 2n – 1; 1 chromosome is missing
TRISOMICS : 2n + 1; 1 chromosome is present 3 times instead of two
TETRASOMICS : 2n + 2; 1 chromosome is present 4 times
DOUBLE TRISOMICS : 2n +1+1; 2 different chromosomes are present 3 times each
NULLISOMICS : 2n – 2; 1 Homologous pair is missing. This is fatal in diploids but
not in polyploids.

HOW DO ORGANISMS GET AN EXTRA CHROMOSOME OR LACK A CHROMOSOME?

NON-DISJUNCTION OF CHROMOSOMES: abnormal separation of chromosomes during meiosis.

XX ----------------------- XX -------------------------- X X
parent meiosis 1 meiosis 11 n+1 n+1 n-1 n-1

XX ----------------------------- X X ----------------------------- X I I
parent meiosis 1 meiosis 11 n+1 n n n-1

n+ 1 and n- 1 gametes produce aneuploid offspring

ANEUPLOIDS IN HUMANS

SYNDROME SEX CHROMOSOME FREQUENCY EXPECTED LIFE

INVOLVED SPAN &
FERTILITY
DOWN M/F TRISOMY (21) 1/700 15 yrs; rarely
reproduce
PATAU M/F TRISOMY (13) 1/15000 Less than 6
months
EDWARDS M/F TRISOMY (18) 1/5000 Less than 1 year
TURNER F XO 1/5000 Normal life span,
sterile
KLINEFELTER M XXY 1/2000 Normal life span,
sterile
METAFEMALE F XXX or XXXX 1/700 Mentally
retarded, nearly
sterile

CHANGES IN CHROMOSOME STRUCTURE

Various environmental agents such as radiation, can cause chromosomes to break apart.
Sometimes the broken ends of one or more chromosomes do not rejoin in the same pattern as
before and this results in chromosome mutations. The types of chromosomal mutations include:

 DELETIONS – chromosome has missing segments. If the missing portion is at the end of
the chromosome, it is called a terminal deletion; if a segment in the middle of the
chromosome is missing, then an interstitial deletion has occurred. Even if only one
 member of a homologous pair is affected, a deletion causes abnormality. If there is a
homozygous deletion, the organism will die - usually as an embryo.

ABCDEFGH----------------ABCDEFGH or ABCFGH or CDEFGH

ABCDEFGH BCDEFGH ABCFGH CDEFGH
Normal terminal deletion intestitial deletion homologous terminal deletion

Eg. in humans, the heterozygous deletion of chromosome # 5p causes the condition ‘cri-
du-chat’. Individuals with this condition have a small head, severe mental retardation,
cries like a cat and dies in early childhood (lives up to 10 yrs).

 DUPLICATIONS – presence of a chromosome segment more than once in the same

chromosome.
ABCDEFGH – normal chromosome
ABCBCDEFGH- tandem duplication
ABCCBDEFGH –reverse duplication
ABCDEFBCGH – displaced duplication

Eg. human cells have multiple copies of the gene that codes for haemoglobin

 INVERSIONS – a segment of the chromosome is turned around 1800. The same genes are
present but in reverse order along the chromosome. This reversed sequence of genes can
lead to altered gene activity.

Paracentric inversion: ABCD.EFGH ABCD.EFGH

ABCD.EFGH ACBD.EFGH

Perecentric inversion : ABCD.EFGH ABCD.EFGH

ABCD.EFGH ABFE.DCGH

The resulting arrangement is no longer called homologous but inversion heterozygotes.

 TRANSLOCATION – the movement of a chromosome segment from one chromosome to

another non-homologous chromosome.
*If translocation occurs between homologous chromosomes, it is termed reciprocal
translocation.

Eg. * 5% of Down Syndrome cases are the result of translocation between chromosomes
21 and 14.