BIO112: MOLECULAR BIOLOGY

AND GENETICS
Mr. Derrick Banda MSc, BSc
 LECTURE 6

GENETICS AND GENE

MUTATIONS
 GENETIC TERMS
• Gene - a unit of inheritance that usually is directly responsible for one trait
or character.
• Allele - an alternate form of a gene. Usually there are two alleles for every
gene, sometimes as many a three or four.
• Homozygous - when the two alleles are the same.
• Heterozygous - when the two alleles are different, in such cases the
dominant allele is expressed.
• Dominant - a term applied to the trait (allele) that is expressed irregardless of
the second allele.
• Recessive - a term applied to a trait that is only expressed when the second
allele is the same (e.g. short plants are homozygous for the recessive allele).
• Phenotype - the physical expression of the allelic composition for the trait
under study.
• Genotype - the allelic composition of an organism.
• Punnett squares - probability diagram illustrating the possible offspring of a
mating.
 GENETICS
What is Genetics?
• Genetics is the study of heredity and variation
of inherited traits (characters).

Heredity is the tendency of offspring to

resemble their parents.

Variation is the tendency of offspring to vary

from their parents.
 GENETICS
What is Genetics?
• Genetics – study of how traits are passed from
parent to offspring.
 GENETICS
• The term ‘Genetics’ was coined by William
Bateson in 1905.

• Gregor Johan Mendel, an Austrian monk, is

known as the “Father of Modern Genetics”.

• The modern concepts of Genetics took birth

from pioneering work on Pisum sativum
(Garden pea)
 What is a GENE?
• A gene is a fundamental unit of heredity. A gene is
a small section of DNA within the genome that
contains the instructions for the production of a
specific protein.

• Gene contain the instructions for our individual

characteristics – like eye and hair colour.

• DNA is the molecule responsible for the inheritance

of traits, and that this molecule is divided into
functional units called genes.
 A GENE
• Each gene contains the information required to build
specific proteins needed in an organism.
 TRAITS (CHARACTERISTICS)
• Traits are determined by the genes on the
chromosomes. A gene is a segment of DNA that
determines a trait.
 GENE MUTATION
• Gene Mutation it is a change in the sequence of a gene
that changes its functions. These changes may be
harmful, beneficial, or have no effect (neutral) on the
individual or cell.
• Mutation may arise during replication and/or
recombination.
• Mutation could be spontaneous or induced by
chemical and physical mutagens.
• Mutation may occur in either somatic or germ cells.
• Mutations that occur in germ cells may be passed to
subsequent generations.
 GENE MUTATION
• Mutation can result in changes in the proteins that are
made. This can be a bad or a good thing.
 SPONTANEOUS AND INDUCED GENE MUTATIONS
Mutation can be caused by:
i. Spontaneous methods
ii.Induction through physical or chemical means
 SPONTANEOUS MUTATIONS
• Spontaneous mutations arise naturally.
• Spontaneous mutations are rare and occur
without any reason.
• It arises due to metabolic errors, replication
errors or due to development errors.
• Larger genes are more prone to spontaneous
mutation because the chance of replication
error is higher in larger genes.
 INDUCED MUTATIONS
• Induced Mutations by physical or chemical mutagens.
i. Chemical: Many chemical mutagens, some exogenous,
some man-made, some environmental, are capable of
damaging DNA. Many chemotherapeutic drugs and
intercalating agent drugs function by damaging DNA.
e.g. nitrous acid and base analogs.

ii.Physical: Gamma rays, X-rays, even UV light can

interact with compounds in the cell generating free
radicals which cause chemical damage to DNA.
 MUTAGENS
• What is a mutagen? A mutagen is a substance or agent that
causes change of the DNA sequence. This change of the
DNA sequence is known as mutation.

• Any agent causing mutation is called mutagen. Mutagens

can be physical, chemical, or biological.

• The ability of a substance to induce the changes in the base

pairs of DNA or mutation is known as mutagenicity.

• Mutagenesis is the process that result in change of DNA

sequence.
 MUTAGENS
• Mutagens can be physical mutagens, chemical
mutagens, or biological mutagens.
TYPES MUTAGENS
 PHYSICAL MUTAGENS
• Mutation are normally very rare. However, exposure to radiation and some
chemicals, such as tar in tobacco smoke, increases the rate of mutation.
• Exposure can cause uncontrolled cell division, leading to the formation of
tumours (cancer).

• Exposure of gonads (testes and ovaries) to radiation can lead to sterility or

to damage to genes in sex cells that can be passed on to children.
 PHYSICAL MUTAGENS
• Physical mutagens are X-rays and UV light.
• X-rays, gamma rays, cosmic rays are ionizing radiation
which ionizes water of the cell to release hydroxyl free
radical (OH). The hydroxyl radical is a powerful oxidizing
agent. Hydroxyl radical oxidises the phosphodiester bond
of DNA. Higher dose of X-rays can even causes death of
an organism.

• UV light is a non-ionizing radiation. It causes the

formation of thymine dimer (Pyrimedine dimer). If two
thymine occur together in one strand of DNA, UV light
causes fusion to form thymine dimer.
Consequences of Radiation Exposure
 CHEMICAL MUTAGENS
• Three types of chemical mutagens are found.
i. Intercalating agent: The chemical intercalate or slip in between two base
pair in Double stranded DNA helix and hence alter the shape of DNA at
that position. Chances of error during replication is higher at this position
causing mutation. Examples; Acridine orange, ethidium bromide,
proflavin
ii. Base analogs: The shape of these chemicals are similar to that of normal
nitrogen bases. So during replication these molecules are incorporated
instead of normal nitrogen bases and hence causes mutation. Example; 2-
aminopurine is analogue to Adenine, 5-bromourcail is analogue to
thymine
iii. Reacting chemicals: These chemical mutagens reacts directly with the
nitrogenous bases of DNA and chemically modify the DNA causing
mutation. Example; Nitrous acid react with nitrogenous bases and
remove amino group from purine and pyriminine.
 TYPES OF MUTATION
• Mutation can be;
i. Base substitutions (Point) mutations- One
base replaced by another in a sequence.

ii.Insertion or deletion mutations (Frameshift)

– Where bases are deleted or inserted in a
sequence.
BASE SUBSTITUTION (POINT MUTATION)
1. Base Substitutions
• Is when one or more bases are replaced by another in a
sequence.

• Base substitution mutations that occur in DNA sequences are

either;
i. Silent
ii. Missense
iii. Nonsense
 BASE SUBSITUTION MUTATION
i. Silent: If a base substitution occurs in the third
position of the codon there is a good chance that a
synonymous codon will be generated. Thus the
amino acid sequence encoded by the gene is not
changed and the mutation is said to be silent.
 BASE SUBSTITUTION MUTATION
ii. Missense: When base substitution results in the
generation of a codon that specifies a different
amino acid and hence leads to a different
polypeptide sequence.
 BASE SUBSTITUTION MUTATION
iii. Nonsense: When a base substitution results in a
stop codon ultimately terminating translation and
most likely leading to a nonfunctional protein.
 FRAMESHIFT MUTATIONS
2. Frameshift (deletions and insertions) mutations -A
mutation that causes all the nucleobases following it to
be shifted.
• Deletions or insertions of nucleotides may results in a
shift in the reading frame or insertion of a stop codon.
• Several nucleotides are inserted or deleted into a
gene. These mutations may shift the reading frame of
translation, resulting in a completely different amino
acid sequence after mutation site.
• These mutations tend to have serious effects on
protein functionality.
FRAMESHIFT (DELETION) MUTATION)
i. Deletion - A deletion results when one or more
base pairs are lost from the DNA. If one or two
bases are deleted the translational frame is altered
resulting in a non-functional product.
 FRAMESHIFT (INSERTION) MUTATION)
ii. Insertions -The insertion of additional base
pairs may lead to frameshift depending on
whether or not multiples base pairs are inserted.
 SOMATIC AND GERM-LINE MUTATIONS
• In multicellular organisms, depending on the cells
that are affected by the mutagen, mutations can be
classified as follows:
1.Somatic mutations
2.Germ-line mutations
 SOMATIC AND GERMLINE MUTATIONS
1. Germline mutations – occur in gametes and can be passed onto
offspring (every cell in the entire organism will be affected)
2. Somatic mutations – occur in a single body cell and cannot be
inherited (only tissues derived from mutated cell are affected)
SOMATIC AND GERMLINE MUTATIONS
 SOMATIC MUTATIONS
• An alteration in DNA that occurs after conception.
Somatic mutations can occur in any of the cells of the
body except the germ cells (sperm and egg) and
therefore are not passed on to children.

• Numerous types of somatic mutations may not be

manifested to affect an individual due to the reparative
and compensative processes of the body. However, a
somatic mutation that alters the cell division patterns of
the cell can eventually result in the formation
of cancerous cells or tissue.
SOMATIC MUTATIONS IN CANCER
 GERMLINE MUTATIONS
• Germline mutations occur in gametes or in the
reproductive cells that produce gametes or sex cells.

• Germline mutations is typically passed down from one

or both parents to the child. Germline mutations are
heritable, meaning they have the ability to be passed
down from generation to generation.

• For example, BRCA gene mutations are a common

cause for families with a strong history of breast or
ovarian cancer. Hereditary cancer testing, such as
BRCA gene testing, has been popular in the western
world for a long time.
 EFFECTS OF MUTATIONS
• Mutations can be lethal or non-lethal and
also, these can be inheritable as well as
non-inheritable.
 EFFECTS OF MUTATIONS
• Beneficial Mutations
• Some mutations have a positive effect on the organism in which they
occur. They are called beneficial mutations. They lead to new versions
of proteins that help organisms adapt to changes in their environment.
Beneficial mutations are essential for evolution to occur. They increase
an organism’s changes of surviving or reproducing, so they are likely to
become more common over time. There are several well-known
examples of beneficial mutations. Here are just two:
• Mutations in many bacteria that allow them to survive in the presence
of antibiotic drugs. The mutations lead to antibiotic-resistant strains of
bacteria.
• A unique mutation is found in people in a small town in Italy. The
mutation protects them from developing atherosclerosis, which is the
dangerous buildup of fatty materials in blood vessels. The individual in
which the mutation first appeared has even been identified.
 EFFECTS OF MUTATIONS
• Harmful Mutations
• Random change in a gene's DNA is likely to result in a protein that
does not function normally or may not function at all. Such mutations
are likely to be harmful. Harmful mutations may cause genetic
disorders or cancer.
• A genetic disorder is a disease caused by a mutation in one or a few
genes. A human example is cystic fibrosis. A mutation in a single
gene causes the body to produce thick, sticky mucus that clogs the
lungs and blocks ducts in digestive organs.

• Cancer is a disease in which cells grow out of control and form

abnormal masses of cells. It is generally caused by mutations in genes
that regulate the cell cycle. Because of the mutations, cells with
damaged DNA are allowed to divide without limits. Cancer genes can
be inherited.
 EFFECTS OF MUTATIONS
• Some of the diseases which are the outcome of
mutation are
i. Retinoblastoma or retinal tumors in children,
ii.Tay-Sachs disease
iii.Phenylketonuria
iv.Color-blindness
v.Cystic fibrosis
vi.Xeroderma pigmentosa
 EFFECTS OF MUTATIONS
• Xeroderma pigmentosa is a condition in which
thymine dimerization from exposure to UV light is
not repaired. Exposure to sunlight results in skin.
 EFFECTS OF MUTATIONS
• Many mutations can actually lead to various diseases. Certain
mutational diseases are inheritable and occur due to mutation in the
germ cell. One such disease is sickle cell anemia, which occurs due
to a single missense mutation at codon 6 of the β-globin gene in
germ cells. This mutation results in the replacement of the glutamic
acid at position 6 in the normal protein by valine. This modification
severely affects the oxygen-carrying protein, i.e., hemoglobin. The
mutated hemoglobin has a highly reduced oxygen-carrying property
and erythrocytes become rigid resulting in the painful passage of the
blood cells and even blockade in the capillaries and tissue damage.
Interestingly, the defective erythrocytes are resistant to malaria and
thus this mutation has been maintained in the African population.
The comparison between the Sickle Cell and
the Normal Red blood cells
END OF LECTURE!
THANK YOU