Ebenezer Marcus

International School & Junior College (CBSE)

#2, Daniel Street, West Banu Nagar, Pudur, Ambattur, Chennai – 53.

Biology Investigatory Project

On
GENETIC MUTATION: TYPES AND ITS CAUSES

Project Done by:

ANUMEHA.R

CLASS XII

Registration Number

AISSCE – 2020-2021
 BONAFIDE CERTIFICATE

EBENEZER MARCUS INTERNATIONAL

SCHOOL & JUNIOR COLLEGE (CBSE)
#2, Daniel Street, West Banu Nagar, Pudur, Ambattur, Chennai – 53.

This is to certify that this project entitled

GENETIC MUITATION: TYPES AND ITS CAUSES

Is a bonafide work carried out by

NAME: ANUMEHA.R
ROLL NUMBER: ____________________

IN THE DEPARTMENT OF BIOLOGY,

Under my supervision

EBENEZER MARCUS INTERNATIONAL SCHOOL &

JUNIOR COLLEGE (CBSE)
#2, Daniel Street, West Banu Nagar, Pudur, Ambattur, Chennai – 600 053.

INTERNAL EXAMINAR SEAL EXTERNAL EXAMINER

Date: Date:
 ACKNOWLEDGEMENT
At the outset I would like to express my gratitude to my
beloved school Ebenezer Marcus International School and
junior college for the opportunity given to me to carry out the
project in biology.

I thank Mrs. D.R. FIDELIS SUJA M.Sc., M.Phil. B.Ed., the

Principal for the incessant support to complete my project.

I would like to express my profound gratitude to my

advisor Dr. C. RAJA RATHI. M.Sc., M.Phil., Ph.D., for her
valuble support, encouragement, supervision and useful
suggestions throughout this research work. Her moral support
and continuous guidance enabled me to complete my project
work successfully.
CONTENT
 Introduction
 Gene mutation
 Types of gene mutation
 Other types of gene mutation
 Chromosome mutation
 How does mutation occur?
 Different types of genetic mutation
 Spontaneous mutation
 Induced mutation
 Somatic mutation
 Germ line mutation
 Morphological mutation
 Lethal mutation
 Conditional mutation
 Biochemical mutation
 Loss of function mutation
 Gain of function mutation
 Temperature-sensitive mutant
 Pleiotropy
 Disorders Caused By Mutation
 Experiment
 Conclusion
 INTRODUCTION

A mutation is a change or alteration happens in a DNA, gene, or chromosome due to

intrinsic or extrinsic factors such as an error in replication or exposure to UV light,
respectively.

The mutation is an important biological process in nature. It can be helpful or harmful. For
instance, the mutation creates variations in nature by providing new alleles and hence helps
in evolution.

On the other hand, a sudden or undesirable mutation can cause cancer and other
harmful genetic disorders.

The word mutation was similar to the French word “mutacioun” which literally means
“process of changing.”

The first one to notice mutation was an English farmer Seth Wright, noticed unusual short-
legs male lambs during 1791.The term “mutation” was coined by Hugo De Vries in 1890.

The basic unit of life is a cell. A cell- a microscopic structure present in every organism. It has
an even tinier nucleus in its center. The material present in the nucleus is known as nuclic
acid (DNA or RNA).

DNA as nucleic acid present in almost every organism and made up of the long chain of
nucleotides. Chain of nucleotides is called as polynucleotides.

Nitrogenous bases- A, T, G and C are the main units of nucleotides besides the sugar and
phosphate. A chain of nucleotides which encodes proteins is known as a gene. If it changes,
the function of gene alters or losses.

The process of transcription and translation is collectively called gene expression. A

mutation can also change gene expression. Likewise, mutation in the structure or number of
chromosomes also results in genetic abnormalities.

The genetic mutations are usually categorized broadly into two categories- gene mutations
and chromosomal mutations.
GENE MUTATION
Mutation or series of mutations occur in the polynucleotide sequence of a gene that
changes the function of it is referred to as gene mutations .

Type of Gene mutations:

Point mutation– Change in the single base of the DNA. It’s often known as single
nucleotide polymorphism

Insertion – Insertion of a base into the gene sequence known as addition mutation.

Deletion– When some bases deleted from the gene sequence it is known as deletion.

Inversion– When some gene sequences are inverted and inserted back into the original
sequence it is known as inversion.
Substitution– When some bases of a gene sequence are replaced by other bases it is
known as substitution.

Duplication– when some bases duplicated in a gene sequence known as duplication.

OTHER TYPES OF GENE MUTATIONS:

Forward mutation:
 Genetic Mutation from wild-type to new mutation is called a forward
mutation. The forward mutation leads to the evolution of new traits in the
population.

Backward mutation:
 A mutation is a unidirectional process, but sometimes some mutation gives the
original (wild-type) allele back to the population, such mutation is known as a
backward mutation.
 It gives the original phenotype back into the population by the occurrence of a
true back mutation and secondary mutation.
 Back mutation is a very rare and unusual phenomenon in nature. In back
mutation, a mutation occurred at the same location as it occurred during forward-
mutation. In simple words, it gives the wild-type codon back to the population.
 In secondary mutation, an occurrence of a new mutation in any place in the
sequence of the gene which gives the original function back or sometimes the
new mutation suppressed the effect of the previous forward mutation.

Copying error:
 Copying error occurs during cell division while replication. If it remains
un-repaired, such mutations will change the genetic code.

Silent mutation:
 It is non-expressive. In silent mutation, a new codon codes for the same amino
acid as the wild-type one.

Mis-sense mutation:
 A codon originated from a nucleotide change that will code for different amino
acids. It can lead to alteration or loss of function in protein.

Nonsense mutation:
 A stop codon added to the DNA sequence that stops protein translation. It stops
protein synthesis because a stop codon ends the protein synthesis results in a
premature protein or truncated protein.
Frameshift mutation:
 Base pair alteration causes abnormal reading frames which ultimately results in
an abnormal protein formation. A specific reading frame has a start codon and a
stop codon. In between both codons, a definite coding sequence is present.
 In a frameshift mutation, alteration in DNA leads to shifting of this reading frame
from one place to another in a genome. So the position of start or stop codon
changes.
CHROMOSOME MUTATION
Change or alteration into the structure or number of chromosomes is known as
chromosomal mutation.

Insertion– When a large section of a chromosome arm is inserted in a chromosome it is

known as insertion.

Deletion– When a section of a chromosome is removed from the chromosome it is

known as deletion.

Duplication– When a section or arm of the chromosome duplicated it is known as

duplication.

Translocation– when a section or arm or some portion of chromosome translocated to

another chromosome.

Balanced translocation: Two segments of roughly of same size are exchanged.

Reciprocal translocation: Reciprocal translocations are more commonly found in

nature. It occurs between two non-homologous chromosomes.

Robertsonian translocation: Robertsonian translocation occurs between two acrocentric

chromosomes. Acrocentric chromosomes are small-short chromosomes with one long q-
arm and a short or very smaller p-arm.
Here long arms of both chromosomes are fused together. Therefore, one chromosome
becomes larger metacentric and another chromosome remains without any arms or only
with centromere.
Inversion– when a section of a chromosome is inverted and inserted back to the chromosome
it is known as inversion.
If inversion occurs in only one arm of the chromosome it is called a paracentric inversion.
The centromere is not involved in paracentric inversion.
If the inversion occurs between two arms of a chromosome it is called a pericentric inversion.
The centromere is involved in pericentric inversion.

Aneuploidy– Change in the number of the chromosome which results in genetic abnormality
is known as aneuploidy.
HOW DOES A MUTATION OCCUR?
Replication error and error in DNA repairing are the intrinsic factors which induce
mutations. While UV rays, X-rays, base analogous, teratogens, and carcinogens are some
of the extrinsic factors which cause mutations.

1. Error In Replication:
Replication is a process of copying the entire DNA. It creates the exact copy of
DNA using the DNA polymerase. However at the end of replication, some DNA
sequences can’t copy properly. Thus gene or DNA sequence can’t replicate
properly and hence it causes mutation.

2. Error In DNA Repairing

Replication errors are repaired by cell’s DNA repair mechanism, however, some
mutations even skip DNA repair.

3. Mutagens: Agents that cause mutations are known as mutagens. For example,
UV rays, base analogous, and chemicals. Mutagens interfere with the base-pairing
or nucleotide structure and result in mutation.
DIFFERENT TYPES OF GENETIC MUTATIONS:
Spontaneous mutation

 Spontaneous mutations occur by metabolic, replication, and developmental errors.

 Spontaneous mutations are rare and occur without any reason. It originated by
birth.
 Larger genes are more prone to spontaneous mutation because the chance of
replication error is higher in larger genes.
 The rate of spontaneous mutation is 10-5 per gene per generation during
replication.

Induced mutation

 An induced mutation is resulted from exposure of an organism to mutagenic agents.

The general mutagenic agents are radiation, UV light and chemicals.
 The UV light is responsible for xeroderma pigmentation and skin cancer.
 Due to the lower energy of the UV light, it can’t penetrate into other tissues but it can
easily penetrate the skin cells and activate oncogenes.
 Chemicals such as alkylating agents and base analogs are common chemical
mutagens.
 Climate change and lifestyle play a major role in acquiring mutations.
Somatic mutation
 Somatic mutations occur in the somatic cells only.
 It doesn’t follow any specific pattern of inheritance.
 Somatic mutation is restricted to some tissue or bodily organs.
 Commonly somatic mutations cause cancer, in most cases.
 The somatic mutation occurs during the mitosis.

Germ-line mutation:
 Only germ cells can undergo fertilization therefore those mutations which are present
in germ cells can only be inherited.
 Mutations occur in egg or sperm, it’s known as germline mutations.
 Germline mutations are inherited and more dangerous than a somatic one.
 Germline mutation occurred during meiosis.
 Germline mutations may or may not affect the parental organism but it will surely
affect the offsprings. Also, the germline mutations are generally non-curable.
 The germline mutations help in evolution by providing new alleles, yet, it may
harmful too.
Morphological mutation:

 The Genetic mutation which affects the physical characteristic or phenotype of an

organism is called a morphological mutation.
 This type of mutation alters the physical properties like shape, size, and color of an
organism.

Lethal mutation:
 A Genetic mutation that causes the death of an organism or affects the survival of an
organism is called a lethal mutation.
 If a mutation causes death in a certain environment then the mutation is known as a
conditional lethal mutation.

Conditional mutation:
 In this type of genetic mutations, the mutant allele causes mutant phenotype in a
certain specific environment or conditions and remains wild type in some other
environment.
Example of Bacteria,

o The conditions which favor the growth of mutant colonies are called restrictive
conditions.
o The conditions which cause the growth of wild-type phenotype are called permissive
conditions.
In this experiment, if some special type of essential amino acid is given into the culture
medium, then the mutant bacteria will grow, in the lack of essential amino acid only wild
type bacteria can grow.
Biochemical mutation:

 Different biochemical pathway inside the cell provides that essential requirement.
 For mutation study, bacteria are the most suitable model organism because of their
unique properties.
 Bacteria or microbial culture which can grow on minimal media are
called prototrophic.
 The biochemical mutant doesn’t have some metabolites which they require to grow
are called auxotrophic. So the require all the essential nutrients like amino acids and
other organic salts.
 Auxotrophic mutants are unable to synthesize essential nutrients like amino acid,
vitamins and nitrogenous bases whereas wild-type strains of bacteria can synthesize
all the essential metabolites.
Loss of function mutation:

 A mutation that causes functional loss of the gene is called a loss of function
mutation.
 Loss of function mutation depends on the condition of inheritance of that mutation. If
the wild-type normal allele is dominant and expressed over mutant allele the loss of
function mutation remains recessive. It is also called a null mutation.

Gain of function mutation:

 Mutation which gives a new function to the gene or gives the original function back to
the gene is called a gain of function mutation.
 These types of mutation are rare.
 In sickle cell anemia-heterozygous condition, individuals remain unaffected but
mutation gives one additional benefit. It protects against the malaria parasite.
Despite, in the homozygous mutant condition, it causes anemia.

Temperature-sensitive mutant:

 Mutant that is growing at one temperature and remains suppressed at another

temperature, is called a temperature-sensitive mutation.
 Most enzyme-coding genes are temperature sensitive because enzymes are activated
at a once specific temperature.

Pleiotropy:
 Pleiotropy is the mechanism in which the mutation in one gene influences more than
one trait or phenotype.
DISORDERS CAUSED BY MUTATION
Some well-known inherited genetic disorders include cystic fibrosis, sickle cell anemia, Tay-
Sachs disease, phenylketonuria and color-blindness, among many others. All of these
disorders are caused by the mutation of a single gene.

Most inherited genetic diseases are recessive, which means that a person must inherit two
copies of the mutated gene to inherit a disorder. This is one reason that marriage between
close relatives is discouraged; two genetically similar adults are more likely to give two
copies of a defective gene to the child.

Diseases caused by just one copy of a defective gene, such as Huntington's diseases, are rare.
Thanks to natural selection, these dominant genetic diseases tend to get weeded out of
populations over time, because afflicted carriers are more likely to die before reproducing.

Scientists estimate that every one of us has between 5 and 10 potentially deadly mutations in
our genes-the good news is that because there's usually only one copy of the bad gene, these
diseases don't manifest.

Cancer usually results from a series of mutations within a single cell. Often, a faulty,
damaged, or missing p53 gene is to blame. The p53 gene makes a protein that stops mutated
cells from dividing. Without this protein, cells divide unchecked and become tumors.

Sickle Cell

These are the sickle-shaped blood cells of

someone with sickle cell anemia, a genetic
disease common among those of African
descent.

Sickle cell anemia is the result of a point

mutation, a change in just one nucleotide in
the gene for hemoglobin. This mutation
causes the hemoglobin in red blood cells to
distort to a sickle shape when deoxygenated.
The sickle-shaped blood cells clog in the
capillaries, cutting off circulation.

Having two copies of the mutated genes cause sickle cell anemia, but having just one copy
does not, and can actually protect against malaria, which is beneficial.
Huntington’s disease
Huntington’s disease is a degenerative brain disorder that causes uncontrolled movements,
emotional disturbances and cognitive decline. It is a single inheritance or monogenic disorder

Huntington’s disease develops due to a mutation on a dominant allele within chromosome 4.

People with this allele will eventually develop the condition.

There is currently no way to stop or slow the progression of Huntington’s disease.

However, certain medications may help a person manage their symptoms. These include
medications to help control involuntary movements and medications to treat mood
shifts, irritability, and depression.

Muscular dystrophies

Muscular dystrophies are a group of genetic conditions that cause muscle damage and
weakness over time. They are due to mutations on the DMD gene.

Muscular dystrophies are X-linked disorders; they affect a gene on the X chromosome. These
conditions are more common in males. This is because males have one X chromosome and
one Y chromosome, whereas females have two X chromosomes. In females, the unaffected X
chromosome can counteract the affected one, but in males, there is not another X
chromosome to do this.

There is currently no treatment available to stop or reverse muscular dystrophies.

Instead, of treatment there are several therapies. Physical therapy, it helps to maintain muscle
strength and flexibility. Respiratory therapy, it helps to maintain the strength of the
respiratory muscles. Speech therapy, for people who have a weakness of the throat or facial
muscles affects speech. Occupational therapy, it helps a person to use assistive devices such
as wheelchairs

Medications that help to slow or control symptoms:

 Glucocorticoids, to increase muscle strength and slow the progression of muscle

weakness
 Immunosuppressants, which may help delay damage to muscle cells
 Anticonvulsants, to help control muscle spasms and seizures
 Antibiotics, to treat respiratory infections
Chromosomal abnormalities

Chromosomal abnormalities are problems that affect a chromosome. Chromosomal

abnormalities involves having a missing chromosome, having an extra chromosome, having a
chromosome that has some kind of structural abnormality

Chromosomal abnormalities usually occur when there is an error is cell division. These errors
usually occur within the egg or sperm, but they can also happen after conception.

It is possible to inherit a chromosomal abnormality from a parent. However, some develop

within a person for the first time.

Chromosomal abnormalities include Down syndrome, Wolf-Hirschhorn syndrome.

Down syndrome

Down syndrome is a type of chromosomal abnormality that affects intellectual and physical
development.

Down syndrome occurs when a person receives an extra copy of chromosome. This means
that each cell within the body contains three copies of chromosome 21 instead of the usual
two copies.

Down syndrome is a lifelong condition. However, various types of therapy can help with a
person’s intellectual and physical development which includes:

 receiving extra help or attention at school

 speech therapy

 physical therapy

 occupational therapy
Wolf-Hirschhorn syndrome

Wolf-Hirschhorn syndrome is a chromosomal abnormality that can affect the entire body.
The major features of this condition include delayed growth and development, reduced
muscle tone, intellectual disabilities, seizures.

Wolf-Hirschhorn syndrome develops due to a deletion of a section of chromosome 4. Person

inherits the condition from a parent who has the chromosomal abnormality.

There is currently no cure for Wolf-Hirschhorn syndrome. However, the following treatments
may help a person manage their symptoms and improve their quality of life:

 Physical or occupational therapy

 Counseling

 Drugs that can help with specific symptoms, such as seizures

Mitochondrial inheritance

Mitochondria is a biological structure that exists inside the body’s cells. They generate most
of the energy that the cells need to carry out their biochemical reactions therefore it is also
known as power house of the cell.

Mitochondrial disorders are a group of genetic conditions that affect DNA within the
mitochondria themselves. These DNA mutations result in the mitochondria failing to produce
enough energy to sustain the body’s cells.

Mitochondrial disorders can affect any organ or part of the body. The symptoms a person
experiences will depend on the part of the body the disorder affects.

Some possible symptoms of mitochondrial disorders include poor growth, muscle weakness,
loss of muscle coordination, visual problems, hearing problems, seizures, developmental
delays, intellectual disabilities, autism spectrum disorder, and diabetes, heart, liver, or kidney
disease and respiratory disorders

Mutations in mitochondrial DNA are inherited maternally. There is currently no cure or

highly effective treatment for mitochondrial disorders.
However, the following treatments may help a person manage them:

 Nutritional management
 Vitamin supplements
 Amino acid supplements
 Medications that help treat specific issues, such as muscle weakness or seizures
MORGAN’S DROSOPHILA EXPERIMENT
Morgan chose the fruit fly (Drosophila melanogaster) for his
genetic studies. They're cheap, easy, and fast to grow.

Morgan's crucial chromosome theory-verifying experiments

began when he found a mutation in a gene affecting fly eye
color. This mutation made a fly's eyes white, rather than their
normal red.

Unexpectedly, Morgan found that the eye color gene was

inherited in different patterns by male and female flies. Male
flies have an X and a Y chromosome (XY), while female
flies have two X chromosomes (XX). It didn't take Morgan
long to realize that the eye color gene was being inherited in
the same pattern as the X chromosome.

The first white-eyed fly he found was male, and when this fly
was crossed with normal, red-eyed female flies, the offspring
were all red. The white allele was recessive.

But when F1 flies were crossed to each other, something strange happened: all of the
female F2 were red-eyed, while about half of the male F2 flies were white-eyed. Clearly, the
male and female flies were inheriting the trait in different patterns. In fact, they were
inheriting it in the same pattern as a particular chromosome, the X.

Earlier, we said that female flies have an XX

genotype and male flies have an XY genotype. If
we stick the eye color gene on the X chromosome
(writing it as w+ plus for red and w for white),
we can use a Punnett square to show Morgan's
first cross.
The predictions match F1 phenotypes, but this set of phenotypes could also be explained by a
gene that is not on the X chromosome, since all the flies were red-eyed (regardless of sex). So
the real test comes when F1 flies are mated to make the F2 generation.
Here is where the X makes the difference. Our Punnett square with the eye color gene on the
X chromosomes correctly predicts that all of the female flies will have red eyes, while half of
the male flies will have white eyes. The male flies get their only X chromosome from their
mother, who is heterogeneous (W+, W), leading to the fifty-fifty split of phenotypes.

Morgan concluded that the gene must lie on, or to be very closely associated with, the X
chromosome. A strong confirmation of this conclusion came from Morgan's student Calvin
Bridges. Bridges showed that rare male or female flies with unexpected eye colors were
produced through nondisjunction of sex chromosomes during meiosis basically, the exception
that proved.

Morgan also found mutations in other genes that were not inherited in a sex-specific pattern.
We now know that genes are borne on both sex and a non-sex chromosome, in species from
fruit flies to humans.
CONCLUSION:

Different types of Genetic mutations randomly occur in the population.

It creates allelic variation in a genome and the new allele originates in the population.
Mutations are not always helpful but also not always harmful.
Any alteration in nature occurs to make us survive on earth. New alleles originate due to
change in the sequence of a gene, which probably happens in our favor.
The sickle allele is in fact originated to make us survive against malaria. In the case of sickle
cell, RBCs become sickle cells, instead of the normal doughnut shape. Hence the malaria
parasite can’t identify it.
It is an evolutionary gift for us, especially, in the African subcontinent where malaria is more
prevalent.
On the other side, some random mutations can cause cancer like a lethal condition.
Thus, we can say, “mutations are helpful but not always or mutations are harmful but not
always.”
Perhaps what I think, random cancer-causing mutations are lethal because it helps to spread
the mutant harmful allele in the population. In this context also, the mutations are helpful.
Besides, using the artificial mutagenesis techniques, any new mutations can be introduced
into the DNA sequence of our interest.
By this, we can create new genetically modified organisms for some experimental purposes.
Polymorphism is a natural phenomenon. A genetic mutation occurs to make us adaptive in
any adverse environment but it may be harmful sometimes. Scientifically we can say, “What
we are today is a result of millions of mutations in the past”.
REFERENCE:

 Griffiths AJF, Gelbart WM, Miller JH: Modern Genetic Analysis. 1999. The
Molecular Basis of Mutation.
 Darlington, C.D. (1942) Chromosome Chemistry and genetic action. Nature
 Chaturvedi (1981), the chemical and physical mutations in the textbook of genetics.
 Thomas Hunt Morgan (1933), Drosophila Eye experiment; mutation in X
chromosome
 https://www.nature.com/scitable/topicpage/genetic-mutation
 https://www.medicalnewstoday.com/articles/genetic-disorders
 https://genetics.thetech.org/about-genetics/mutations
 https://openoregon.pressbooks.pub/ what-kinds-of-gene-mutations
 https://www.khanacademy.org/science/ap-biology/heredity/chromosomal-inheritance
 https://geneticeducation.co.in/genetic-mutations-definition-types-causes-and-
examples