Unit 18 Mutations
Key Unit Competence
To be able to describe the types, causes and effects of mutation in organisms.
LEARNING OBJECTIVES
At the end of this unit, the learner will be able to:
• Define mutation.
• Describe types of mutation and causes of mutations.
• Explain the significance of mutations.
• Make a chart illustrating and summarising different kinds of gene and chromosomal
mutations.
• Distinguish between gene and chromosomal mutation.
• Use a thin clay log composed of different colours to represent different chromosomes.
• Manipulate the clay to show how an inversion can occur.
• Explain that gene mutation occurs by substitution, deletion, inversion and insertion of base
pairs in DNA. Outline how such mutations may affect the phenotype.
• Outline the effects of mutant alleles on the phenotype in the following human conditions:
albinism, sickle cell anaemia, haemophilia and Huntington’s disease.
• Explain the relationship between genes, enzymes and phenotypes with respect to the gene for
tyrosinase involved in the production of melanin.
• Explain how a change in the base sequence of the gene for haemoglobin results in abnormal
haemoglobin and sickle-shaped red blood cells.
• Explain that the environment may affect the phenotype.• Use internet to search simulations of mutations and deduce the findings.
INTRODUCTORY ACTIVITY
After the 1945 Hiroshima and Nagasak atomic bomb, the survivors and their offspring developed
many health problems such as blood cancer (Leukemia), thyroid cancer, polydactyly etc.
How the atomic is related to health problem?Why these health problems of 1945 have effects on children borne many years later?
18.1 MUTATIONS: INTRODUCTION
ACTIVITY 1
After the 1945 Hiroshima and Nagasak atomic bomb, the survivors and their offspring developed
many health problems such as blood cancer (Leukemia), thyroid cancer, polydactyly etc.
How the atomic is related to health problem?Why these health problems of 1945 have effects on children borne many years later?
Nothing was known about mutations before 19th century. Darwin first noticed some sudden
changes in the organisms which he called as “sports”. De Vries (1901) observed several, sudden
changes in Oenothera lamarckiana, and called them mutations. Several sudden mutations were
observed, for example, Ancon sheep (Figure 18.1) is a short legged variety which appearedsuddenly in 1791 and hornless cattle developed from horned cattle in 1889.
Figure 18.1: Ancon sheep with its normal parents
With the work of G. Mendel, inheritance of characters was established and subsequent work
by several researchers firmly established that DNA constitutes the genetic material of any
individual and it is very faithfully replicated and passed on to the offspring to conserve the
parental characters in all subsequent generations. However, once in a while, the process becomes
erratic for various reasons and alterations are seen in the DNA. Mutation is the sudden change
in the genetic material of an individual.
In this unit, you will study the different types of mutations, how are they produced, their effect
on phenotype and what role environment plays in the production of a phenotype. Finally,
we will discuss as to why a detailed study of mutations is helping us not only to understandevolutionary process better, but also find the ways of treating cancer.
18.2 TYPES OF MUTATIONS
ACTIVITY 2
Have you noticed the variations which run in the families? It means it can pass from one
generation to another generation.Discuss more such examples.
Mutations can broadly be categorized as somatic and germ-line, depending on whether mutation
occurs in a somatic cell or gamete. If mutation occurs in a somatic cell in a particular tissue,
it may not affect the functioning of the tissue as the tissue may be composed of hundreds of
normal cells. However, if a mutation occurs in a gamete, upon fertilization the zygote andhence all cells of offspring will carry the mutation.
Mutations can also be classified as shown in the following chart.
Although all mutations occur in genetic material altering the structure of DNA, consequences
of different types of mutations are very different. Table 18.1 compares the attributes of genemutations and chromosomal mutations.
ACTIVITY 3
Aim: To discuss the types and significance of mutations with the help of computer simulations.
Materials Required:
DNA sequences of different human proteins
Genetic code table
Genetic code table
Types of amino acid table
Notebook
Tetrahedron dice with names of each nucleotide (A, C, G and T).
Procedure:
1. First transcribe the given DNA sequence into mRNA sequence.
2. Translate mRNA sequence into amino acids with the help of genetic code table.
3. Note down the sequence of amino acid for protein.
4. Now randomly decide any nucleotide to change of given DNA sequence. (Choose by your
favourite number, your birthday date..... completely random). Now roll the tetrahedron dice
and look for the nucleotide. Replace it with new nucleotide. Consider it mutation 1.
5. Note down nucleotide and replace the original nucleotide with new nucleotide. There can bedifferent possibility. Make a table as given below and record your observation.
6. Record your observation for mutation 1.
7. Repeat it thrice (for three mutation) from step 4 to 6, randomly choose any nucleotide to
mutate and record your observation.
8. Discuss the types of mutations in the class.
For deletion mutation
9. Now randomly decide any nucleotide to delete in given DNA sequence. Suppose we mutate
nucleotide number 10.
Note down DNA sequence. Consider it deletion mutation.
10. Transcribe the new sequence into mRNA sequence.
11. Translate the mRNA sequence into protein.
12. Note down its effect.
For Insertion mutation
13. Now randomly decide any new nucleotide to insert at random site in given DNA sequence.
Note down DNA sequence. Consider it deletion mutation.
14. Transcribe the new sequence into mRNA sequence.
15. Translate the mRNA sequence into protein.16. Note down its effect.
18.2.1 GENE OR POINT MUTATIONS
Gene or point mutations involve single nucleotides and can occur by one of the following
mechanisms (Figure 18.2):
Substitution is the replacement of one base by another. One purine replaced by another purine
or pyrimidine replaced by another pyrimidine is called transition. However, pyrimidine replacing
purine or purine replacing pyrimidine is called transversion.
Silent mutation, when the triplet codon continues to code for the same amino acid because
genetic code is degenerated, or the amino acid substituted has similar chemical property causing
no change in the function of the protein or the change has occurred in non-coding regionof DNA.
Missense mutation, when substitution of a base produces a codon that causes incorporation
of a different amino acid. If the amino acid added is chemically similar to the original amino
acid, it is called conservative missense mutation but if the amino acid added is chemically
dissimilar, it is called non-conservative missense mutation.
Nonsense mutation, when substitution of a base leads to the formation of a stop codon,
terminating protein synthesises at that point. Polypeptide, thus formed, is incomplete andhence non-functional.
Figure 18.2: Consequences of point mutation
Frame-shift mutation here insertion or deletion of bases alters the reading frame of the genetic
code which is comma-less, causing the different sequences of amino acids being coded from
the point of mutation onwards. This type of mutation is called frame-shift mutation and this
has far reaching consequences on protein function. Effect of this mutation in not confined to
just one amino acid replacing another but the entire sequence of amino acids in the proteingets altered (Figure 18.3) and the protein becomes totally non-functional.
Figure 18.3: Frame-shift mutation
18.2.2 Chromosomal Mutations
ACTIVITY 4
Aim: To manipulate a thin clay log composed of different colours to represent different genes
in order to show how an inversion can occur.
Materials Required:
Thin clay log composed of different colours
Notebook
Colour markers
Scale
Procedure:
1. Just consider the thin log as single chromosomes, assemble five different colours to representas gene such as A, B, C, D and E.
3. Reunion the broken parts in inverse manner.
4. Observe the order of genes after reunion of fragments in inverse manner.
5. Compare it with original order of genes.
6. Discuss your observation in the class.7. Enumerate the effect of inversion in phenotype of organism.
Whenever breaks occur in chromosomes, their structures change. If a chromosome or set of
chromosomes shows more than one break followed by reunion, chromosomal rearrangements
are formed. If a break occurs in a chromosome followed by loss of the fragment, it is called
deletion, resulting in loss of genetic information. On the other hand, if a segment occurs more
than once, it results in gain of genetic information and is called duplication. If a chromosome
breaks at two points and fuses again but in reverse order, there is no loss or gain of genetic
information but it alters the sequence of genes in the chromosome and is called inversion.
If breaks occur in non-homologous chromosomes, and the broken fragment from one joins
another non-homologous chromosome, it results in translocation, altering linkage relationships(Figure 18.4).
Figure 18.4: Structural changes in chromosome
Whenever the number of chromosomes gets changed, it results in Numerical changes in
chromosomes. It happens due to non-disjunction, failure of homologous chromosomes to
segregate at anaphase, leads to monosomy (2n – 1) and trisomy (2n + 1). Sometimes fertilization
of ovum by two sperms can produce triploidy and fertilization of diploid gametes or doublingof chromosomes can produce tetraploidy
18.2.3 Differences between Gene and Chromosomal Mutations
ACTIVITY 5
Aim: To discuss the differences between gene and chromosomal mutation and one possible
effect on an organism.
Materials Required:
Red colour clay Beads, log made up of clay, notebook
Procedure:
1. In log, make 5 beads of red colour clay and number it 1 to 5.
2. Now consider the beads as gene and log as chromosome.
3. First in the log, try to change any bead. Either break it by deleting some part of clay material
from it or paste some extra clay to it or replace the clay with same and different colour clay.4. Note down your observation according to the following table:
5. Now take the log, do the following changes:
(a) cut the log.
(b) cut the log at two sites and paste it in opposite orientation.
(c) Add the clay beads of same colour.
(d) Add the clay beads of different colours.(e) Note down your observation according to the following table:
6. Discuss the effect of gene and chromosome mutation on the phenotype of the organism with
the help of example.
Table 18.1: Gene mutation vs chromosome mutation
18.3 CAUSES OF MUTATIONS
Have you ever wondered for the causes of variation? Sometimes we say its spontaneous or
sometimes we say don’t stand in sunlight for so long, or Nuclear weapons or World War II
has prolonged mutagenic effect on the victims or don’t take particular medicine, it might be
mutagenic. So what could be the causes of mutation? Discuss among your friends.
(i) Random mutations can occur spontaneously due to chance as:
(a) DNA replication errors:
• Normally each base exists in its more stable keto form and is responsible for the
normal Watson-Crick base pairing of T with A and C with G. However, under
certain physiological conditions, rare imino and enol forms (tautomers) of the
bases are present, leading to altered base pairing affinities.
• If by chance, there is looping out of DNA from the template strand, it may be
missed by DNA polymerase, resulting in deletion mutation. Similarly, if additional
untemplated base is synthesised by DNA polymerase, addition mutation results.
(b) Spontaneous chemical changes include depurination and deamination:
• When bond breaks between the base and the deoxyribose sugar, purine is removed
from the DNA, resulting in an apurinic site. Thousands of purines are lost in each
mammalian cell cycle. If these apurinic sites are not repaired, DNA polymerase
will not be able to add a complementary base and will dissociate from the DNA.
• Removal of amino group from a base is called deamination. Deamination of
cytosine produces uracil. As uracil is not a normal base for DNA, repair system
can correct the change. However, if not corrected, adenine will pair up with uracil,
ultimately, causing a change from C-G to T-A, a transition mutation.
DNA also contains small amounts of 5-methylcytosine (5mC) in place of normal
base cytosine. Deamination of 5mC produces thymine, a normal base in DNA and
hence not corrected. Therefore, 5mC results in C-G to T-A transitions.
(ii) Induced mutation happens due to mutagens (agents that induce mutations). It can bephysical mutagens or chemical mutagens (Figure 18.5).
Figure 18.5: Physical and chemical mutagens
(a) Radiation: H. J. Muller was the first to show, in 1927, that mutation can be induced by
X ray treatment. High energy rays collide with atoms and cause the release of electrons,
leaving positively charged-free radicals or ions. These ions, in turn, collide with other
molecules, causing release of further electrons. Thus, as the rays pass through the tissue,
they leave a core of ions along its entire track. This process of ionization can occur
by background radiation or be induced by machine-produced X rays, protons, and
neutrons, as well as by alpha, beta, and gamma rays released by radioactive isotopes of
the elements. Ultraviolet rays, though have less energy, can raise electrons in the outer
orbitals to higher energy level called excitation. When molecules contain atoms either
in ionic state or excited state, they become chemically less stable and thus, more prone
to change, making radiation as powerful mutagens. Energy of X rays can also cause
physical breaks in chromosomes, thus resulting in the loss of chromosome segments or
changes in chromosome structure (deletion, duplication, inversion, translocation).
Mutational effect of ultraviolet (UV) radiation was demonstrated by Edgar Altenburg in
1928. UV rays are strongly absorbed by pyrimidines, especially thymine, leading to the
formation of thymine dimmers. Thymine dimers interfere with DNA replication andDNA repair mechanism, causing mutation in DNA.
The damage by radiation has been shown in Figure 18.6.
Since radiation affects large segments of chromosome at the same time, a number of charactersget altered simultaneously, but molecular details cannot be studied.
Figure 18.6: Damage to DNA by physical mutagens – radiations
(b) Chemical: C. Auerbach first discovered the mutagenic effects of mustard gas and related
compounds during World War II. Bhopal gas tragedy in India in December 1984 resulted
in the death of 2500–6000 individuals, affecting adversely 200,000 people. Tragedy
occurred with the release of methyl iso cyanate (MIC) in the form of gas and more than
21 chemicals in the MIC storage tank. A number of tests provided evidence that MIC is
capable of inducing chromosomal damage.
People working in nickel and asbestos refineries, rubber industry, leather industry, coal tars,
wood dust are routinely exposed to a number of mutagenic and potentially carcinogenicagents.
Chemical mutagens are of two types:
(a) That are mutagenic to both replicating and non-replicating DNA, e.g., alkylatingagents (Figure 18.7) and nitrous acid (Figure 18.8).
Figure 18.7: Alkylating agents (EMS) change bases such that their Hydrogen
bonding pattern alters. For example, guanine gets changed to ethylguanine and pairswith thymine instead of cytosine.
Mutagenesis by Nitrous Acid (HNO2)
Figure 18.8: Nitrous acid leads to deamination of cytosine and adenine
which get change into uracil and hypoxanthine.
(b) That’s mutagenic only to replicating DNA, base analogs and acridine dyes.
Base analogs are structurally very similar to normal bases of nucleic acids and thus, can beincorporated mistakenly in place of the normal ones. However, once incorporated, they alter base
pairing affinities, e.g., 5-bromouracil (Figure 18.9), a thymine analog, undergoes a tautomeric
shift and pairs with guanine. During DNA replication, if 5-bromouracil is present in its enol
form, it will be added opposite guanine in the template strand causing AT to GC transition(Figure 18.10).
Figure 18.9: 5-bromouracil–Base analog of thymine and its tautomeric forms (keto and enol)
Figure 18.10: 5-bromouracil causes mutation while DNA replication
Acridine dyes intercalate DNA sequences (Figure 18.11) and stabilize DNA looping which
might be missed by DNA polymerase resulting in deletion or addition of genetic material
causing frame shift mutation.
Figure 18.11: Acridine dyes – intercalating agent causing frameshift mutation
APPLICATION 18.1
1.Complete the sentence with appropriate terms:
(i) Substitution of one base by another may lead to ................................... or ..................
mutation.
(ii) Now disjunction of chromosomes can lead to ................. or ................. .
(iii) Induced mutation happens due to ................. and ................. .
(iv) If a chromosomes breaks and fuses again in reverse order, it is called ..............
2.
Suggest why:
a) A mutation in which one nucleotide of a triplet code is altered often makes no difference to
the protein molecule coded by the DNA.
b) The addition or deletion of three nucleotides in the DNA sequence of a gene often has less
effect on the encoded protein than the addition or deletion of a single nucleotide.3. In most people, the first amino acids in their β-globin polypeptide chains are:
The DNA triplet for the sixth amino acid (Glu) in most people is CTT. In some people this
DNA triplet is CAT.
a) What type of mutation is the change from CTT to CAT?
b) Use the genetic code below to identify the amino acid in the β-globin polypeptide chains
of people with this mutation.c) State the consequences for a person of having two copies of the mutated gene.
18.4 EFFECTS OF MUTATIONS ON PHENOTYPES
Spontaneous or induced mutagens cause changes in genotype which influences the phenotype.
The phenotype can be physiological, morphological, biochemical, anatomical etc. So let’s think
of effect of mutation on phenotype.
A gene represents the smallest unit that can code for protein. Gene is made up of DNA consisting
of four nucleotides present in a particular sequence, which, when read in triplet codons, code
for a particular amino acid sequence of a protein. Proteins play a number of important roles in
the body, such as enzymes, hormones, structural etc. Whenever nucleotide sequence in DNA
changes, it can lead to alteration in amino acid sequence affecting the function of the protein.
For example:
Albinism is caused by an autosomal recessive mutation. Tyrosine is converted to DOPA by
the enzyme tyrosinase (Figure 18.12) and DOPA is converted to melanin, the pigment whichgives colour to the skin.
Figure 18.12: A biochemical reaction for the production of skin pigment melanin (left). The mutation in
gene responsible for the formation of tyrosinase leads to change in phenotype resulting in albinism (right)where affected person have white skin, white hairs and red eyes.
Melanin absorbs light in the ultraviolet (UV) range and protects the skin against UV radiation
from the sun. If a mutation occurs in the gene responsible for production of tyrosinase, tyrosine
cannot be converted to DOPA and melanin cannot be produced. Therefore, people with sucha mutation have white skin, white hair and red eyes and are very sensitive to light.
ACTIVITY 6
Aim: Use charts and illustrations to show how sickle cell anaemia is inherited and outline the
features of the offspring with or without sickle cell anaemia.
Materials Required:
Charts (pedigree tree) and literature about sickle cell anaemia
Notebook
Procedure:
1. Read charts and literature about sickle cell anaemia.2. For inheritance, try to look for sickle cell anaemic patients’ family history (pedigree tree).
3. Observe the following points:
• Whether trait is seen in every generation or it skips generation Whether the affected
person has unaffected parents or affected parents
• Whether the trait is limited to particular sex or randomly happens in both the sexes.
4. Note down the inheritance pattern (recessive/dominant and autosomal/X-chromosome/
Y-chromosome linked).
5. Discuss your observations in the class.
6. Based on effect of mutation on phenotype, tabulate effect of sickle cell anaemia on theaffected offspring in comparison with offspring without disease.
7. Discuss your observations in the class.
Sickle-cell anaemia is a disease which is caused due to synthesis of abnormal haemoglobin,
the protein present in red blood cells for transporting oxygen. This disease was first studied by
J. Herrick, who found that red blood cells in patients suffering from the disease have the
following characteristics:
• Lose their characteristic disc shape, become sickle-shaped whenever oxygen tension becomes
low (Figure 18.13),
• Rupture very easily thus causing anaemia.
It has also been found that sickle cells don’t easily squeeze through the capillaries (Figure 18.14)
as they are not flexible. This leads to blockage of capillaries, not letting blood flow into tissuesdepriving them of oxygen and ultimately causing tissue damage.
Figure 18.13: Red blood cells become sickle shaped in sickle cell anaemia
Thus, people suffering from sickle cell anaemia can have a number of health problems like
heart failure, pneumonia, paralysis, kidney failure, abdominal pain, etc. Survival rate of such
patients is very low. Disease occurs in a milder form and is known as sickle cell trait whereinpatients show some symptoms in areas of low oxygen tension but do survive.
Figure 18.14: Sickle shaped red blood cells are not able to squeeze through
the capillaries leading to blockage in capillaries
Work of L. Pauling showed that normal people made one type of protein haemoglobin, while
people suffering from sickle cell anaemia had another type of haemoglobin and people with
sickle cell trait had 1:1 mixture of two types of haemoglobins. Thus, it was hypothesized that
people with sickle cell trait were heterozygous, carrying two different alleles and making two
types of haemoglobins, Hb-A and Hb-S; normal people were homozygous and making one
type of haemoglobin, Hb-A and people with sickle cell anaemia were homozygous, making
one type of haemoglobin, Hb-S.
Haemoglobin consists of four polypeptide chains, two alpha and two beta, each of which is
associated with a heme group to bind oxygen. V. M. Ingram, on comparing the amino acid
sequence of Hb-A and Hb-S, found that while beta polypeptide of Hb-A had glutamic acid
(with a negative electric charge) at the sixth position, beta polypeptide of Hb-S had valine (with
no electric charge) at the same position. This substitution of amino acids (Figure 18.15) causesthe beta polypeptides to fold up in a different way causing sickling of red blood cells.
Figure 18.15: Substitution of single nucleotide in beta S chain (shown in red) resulting in change in
6th amino acid and different type of hemoglobin Hb-S
Haemophilia normally, we find that after minor injury or prick, bleeding automatically stops
after a brief period. Excessive bleeding is prevented by the presence of clotting factors which
work in a cascade-like fashion. However, there are individuals who continue to bleed for long
periods of time even with minor bruises and may also show spontaneous bleeding. This bleeding
disorder is called haemophilia. Haemophilia is of two types: haemophilia A and haemophilia
B. Though both types occur due to a defect in blood clotting process, the two are a result of
mutations in different genes. Haemophilia A (also called classical haemophilia) is more common,
occurring with a frequency of 1 in 4000 males, and is due to deficiency of blood clotting factor
VIII. Haemophilia B (also known as Christmas disease) is less common, occurring with a
frequency of 1 in 20,000 males, and is due to deficiency of blood clotting factor IX. As the geneF8, coding for factor VIII and gene F9, coding for factor IX are present on X chromosome, a
single copy of either of the mutant genes can cause this disorder in males whereas females will
show the disorder only when homozygous for the mutant alleles. This accounts for the higherfrequency of the disorder seen in males in the population.
Huntington disease: All individuals have Huntington gene which codes for huntingtin protein.
Although it is synthesized by all cells, its critical function is seen in the brain where it interacts
with other proteins in the nerve cells. Addition of CAG repeats in Huntington gene in excess
of the normal number increases the number of glutamines in the protein, causing misfolding of
the protein and a mutant phenotype. This protein accumulates in nerve cells, causing extensive
damage. Symptoms include involuntary movements and progressive central nervous system
degeneration. Although Huntington disease is found to be due to autosomal, dominant allele,
expression of this allele begins only by the age of thirty years by which time the parents havealready passed on the gene to their offspring.
18.5 EFFECT OF ENVIRONMENT ON THE EXPRESSION OF PHENOTYPE
Have you ever thought if identical twins get separated at the time of birth and reared separately
in different regions of earth with varied environment, will they be phenotypically identical?
Discuss among your friends and teachers.
It is not always true that phenotype is completely reflected by genotype. Although our phenotype
is governed by our genotype, environment also plays a very important role. It is the close
interaction between genotype and environment that determines the phenotype shown by any
individual. This can be appreciated by the following examples.
(a) A person who has normal genes for making haemoglobin but lacks sufficient iron in
the diet develops anaemia. Phenotype of this individual can be reversed by including
sufficient iron in the diet.
(b) Individual with normal genes can make adequate amounts of thyroid hormone, thyroxine;
yet, in the absence of sufficient dietary iodine, he may develop hypothyroidism.
(c) Surrounding temperature can have an important influence on phenotype of individuals
by affecting kinetic energy of reacting substances. Plant evening primrose shows red
flowers when grown at 23°C and white flowers when grown at 18°C. Siamese cats and
Himalayan rabbits (Figure 18.16) show white fur on all parts except nose, ears and paws,
as the wild type enzyme responsible for pigment production is functional at the lower
temperature present in extremities, but it loses its catalytic activity at the slightly highertemperature found in the rest of the body.
Figure 18.16: Siamese cats and Himalayan rabbits
(d) Individuals who are born with a deficiency of phenylalanine hydroxylase enzyme needed
to convert phenylalanine to tyrosine, concentration of phenylalanine builds up in the
body, especially in the brain causing neurological damage. Phenylalanine free diet allows
them to lead a near normal life, without showing the effects of mutation.
(e) Every day, we are exposed to a large number of chemicals in our environment such as
food additives, colouring agents in food items, textile dyes, cosmetics, pesticides, industrial
compounds and so on. Some of these chemicals have mutagenic effects, and can causegenetic diseases.
18.6 SIGNIFICANCE OF MUTATIONS
Although the term ‘mutation’ was not used by Mendel, he was able to deduce that genetic
characters are controlled by unit factors that exist in pairs in individual organisms and if two
unlike unit factors exist in the same individual, one unit factor is dominant to the other, which
is called recessive. Later studies revealed the true nature of these unit factors which are now
called genes. As seen in the sections above, mutations have played very important roles as
discussed below.
(i) Role in disease: As studied in earlier sections, mutations have been responsible for a
number of diseases such as sickle cell anaemia, haemophilia, Huntington disease, and
albinism. Each individual has tumour suppressor genes and mutation in any of thesegenes can lead to the development of tumours.
(ii) Role in evolution:
(a) Mutations play the most important role of creating new alleles. If there were no
different alleles, all individuals would be homozygous at all loci. Presence of different
alleles in individuals of a population is responsible for the diversity seen in any
population. For example, blood group alleles IA, IB and IO. So mutation can bring
about change in genetic constitution of an organism. So mutations bring genetic
polymorphism in population which may or may not lead to evolution.
(b) Furthermore, it has been observed that certain African countries show higher incidence
of sickle cell allele as compared to other regions. Sickle cell allele somehow confers
protection against malaria and hence occurs with higher frequency in those regions
where malaria is prevalent. Individuals homozygous for sickle cell allele do not survive
as oxygen transport to tissues is affected and individuals homozygous for the normal
allele may suffer from malaria. Hence, mutant allele in this case happens to confer
an advantage in the heterozygous condition.
(c) Mutations have another very important consequence. Rapid rate of mutation in
bacteria and viruses has helped them evolve resistance not only to our immune
system but also to various antibiotics. Thus, treatment against diseases caused by
these microbial organisms is becoming increasingly difficult.
(iii) Role in genetic research: Humans have around 20,000 genes. Although, scientists know
the functions of a number of genes, vast majority of the genes have still not been assigned
function. To study the function of a gene, researchers induce mutations in specific genes
and look for possible effects. Thus, induced mutagenesis is helping us gain insight into
genetics of cell cycle control points and hence the cells becoming cancerous. Cytogenetic
studies have revealed a high degree of correlation between chromosomal rearrangements
and leukaemias.
(iv) Mutations play an important role in agriculture as well by providing diversity of alleles
which may confer stress resistance, yield and regional adaptability.(ii) Role in evolution:
(a) Mutations play the most important role of creating new alleles. If there were no
different alleles, all individuals would be homozygous at all loci. Presence of different
alleles in individuals of a population is responsible for the diversity seen in any
population. For example, blood group alleles IA, IB and IO. So mutation can bring
about change in genetic constitution of an organism. So mutations bring genetic
polymorphism in population which may or may not lead to evolution.
(b) Furthermore, it has been observed that certain African countries show higher incidence
of sickle cell allele as compared to other regions. Sickle cell allele somehow confers
protection against malaria and hence occurs with higher frequency in those regions
where malaria is prevalent. Individuals homozygous for sickle cell allele do not survive
as oxygen transport to tissues is affected and individuals homozygous for the normal
allele may suffer from malaria. Hence, mutant allele in this case happens to confer
an advantage in the heterozygous condition.
(c) Mutations have another very important consequence. Rapid rate of mutation in
bacteria and viruses has helped them evolve resistance not only to our immune
system but also to various antibiotics. Thus, treatment against diseases caused by
these microbial organisms is becoming increasingly difficult.
(iii) Role in genetic research: Humans have around 20,000 genes. Although, scientists know
the functions of a number of genes, vast majority of the genes have still not been assigned
function. To study the function of a gene, researchers induce mutations in specific genes
and look for possible effects. Thus, induced mutagenesis is helping us gain insight into
genetics of cell cycle control points and hence the cells becoming cancerous. Cytogenetic
studies have revealed a high degree of correlation between chromosomal rearrangements
and leukaemias.
(iv) Mutations play an important role in agriculture as well by providing diversity of alleleswhich may confer stress resistance, yield and regional adaptability.
APPLICATION 18.2
1. Complete with appropriate terms:
(i) Tell the cause of the following diseases
(a) Sickle cell anaemia
(b) Huntington disease
(c) Dawn’s syndrome
(d) Albinism
(ii) .................... have helped develop resistance in virus and bacteria.2. Can a mutation in a somatic cell be lethal?
18.7 SUMMARY
I. Mutation, types and their effects on phenotype
• Mutation is any permanent change in the genetic material of an organism. Somatic
mutations are not passed to offspring whereas germinal mutations are heritable.
• Point mutations refer to changes occurring in single nucleotides.
• Substitution of one base by another may lead to silent (no change), missense (altered
codon) or nonsense (stop codon). Change is confined to single codon.
• Altered codons lead to the incorporation of a different amino acid altering the function
of the protein. Examples are seen in diseases like sickle cell anaemia, haemophilia, and
albinism.
• Insertion or deletion of a base changes the frame of reading the genetic code, resulting
in frame shift mutations. Genetic code being comma-less, addition or deletion of one
base alters all subsequent codons, coding for a sequence of amino acids which are totally
different from the original sequence.
• Chromosomal mutations refer to changes in structure or number of chromosomes.
• Chromosome breakages can cause deletion (loss of genetic material), duplication (gain
of genetic material), inversion (fusion of broken segments in opposite orientation)
or translocation (fusion of a part of one chromosome to another, non-homologous
chromosome).
• Non-disjunction of chromosomes can lead to monosomy (2n – 1) or trisomy (2n + 1).
Example of monosomy is Turner’s syndrome and example of trisomy is Down’s
syndrome.
• Addition of haploid sets to the chromosome complement of a cell can change the ploidy
level creating triploid, tetraploid individuals. This can occur whenever two sperms happen
to fertilise a single ovum, creating a triploid situation or a diploid egg is fertilised by a
diploid sperm (all chromosomes fail to disjoin). This has given rise to newer varieties of
plants such as seedless bananas.
II. Causes of mutations
• Chance effects like mistakes during DNA replication, hydrolysis.
• Ionizing radiation for example X rays, protons, neutrons and alpha, beta and gamma rays
emitted by radioactive elements have high energy and can penetrate the tissues causing
damage to DNA in a number of ways depending on the dose.
• Non-ionizing radiation for example UV rays don’t penetrate tissues because of low energy
but are strongly absorbed by nitrogenous bases, esp. thymine, causing the formation of
thymine dimers. This makes them highly mutagenic and excessive exposure to solar
radiation can lead to development of skin cancers.
• Chemical mutagens belong to two classes: one which produces mutations in replicating
and non-replicating DNA for example alkylating agents, nitrous acid and the other
produces mutations only in replicating DNA for example acridine dyes, base analogs.
• These chemicals generally produce mutations by altering base pair affinities.
• A number of common chemicals routinely encountered in environment such as bromine,
pesticides, food additives, etc., may work the same way and thus potentially carcinogenic.
• A number of these chemicals have found in treating cancers.
III. Effects of environment on the phenotype
• Phenotype of any organism is the result of interaction of genotype and environment.
• Interaction may be due to the effect of temperature on enzyme activity.
• Effect of mutant allele can be minimized by modifying the environment for example,
children born with phenylketonuria may lead a near normal life if fed on diet free of
phenylalanine.
IV. Significance of mutation
• Majority of new mutations are generally deleterious, resulting in disease; some mutationsare adaptive for example, sickle cell allele conferring protection against malaria.
18.8 GLOSSARY
• Chromosome mutation: In values charge in chromosome structure due to leakage of
chromosome.
• Mutagens: Any chemical or physical agent that came mutations.
• Mutations: It is a permanent alteration of the nucleotide sequence gene mutation. Involvesof geneme of an organism single nucleotide change.
END UNIT ASSESSMENT 18
Do all these exercises in your exercise book.
I. Choose whether the given statements are True (T) or False (F)
1. Mutations can broadly be categorized as somatic and germ-line, depending on whether
mutation occurs in a somatic cell or gamete.
2. When breaks occur in chromosomes, their structures do not change.
3. Induced mutation happens due to mutagens (agents that induce mutations).
4. Removal of amino group from a base is called deamination.
5. Albinism is caused by an autosomal recessive mutation.
6. Haemophilia A and Haemophilia B are a result of mutations in different genes.
7. There is no interaction between genotype and environment that determines the
phenotype shown by any individual.
8. Sickle cell anaemia is due to a dominant sex-linked allele.
9. Mutagens are DNA sequences which get changed due to radiations and chemicals.10. Mutation has important role in bacterial resistance to antibiotic
II. Multiple Choice Questions
1. A point mutation that changes a codon specifying an amino acid into a stop codon
is called
(a) missense mutation (b) nonsense mutation
(c) frame shift mutation (d) silent mutation
2. Sickle cell anaemia results because of
(a) deletion mutation (b) insertion mutation
(c) substitution mutation (d) chromosomal mutation
3. In mutational event, when adenine is replaced by guanine, it is a case of
(a) transition (b) transcription
(c) transversion (d) frame shift mutation
4. Which of the following is not ionising radiation
(a) X rays (c) UV rays
(b) cosmic rays (d) alpha rays
5. Which of the following chemicals can affect non-replicating DNA?
(a) nitrous acid (b) Acridine dyes
(c) bromouracil (d) None of the above
6. Phenotype of individual depends upon
(a) environment only (b) genotype only
(c) environment and genotype (d) mutagens
7. Which is the type of chromosome structure mutation?
(a) Aneuploidy (b) Polyploidy
(c) Trisomy (d) duplication
8. Which is the example for gene mutation?
(a) Turner syndrome (b) Klinefelter syndrome
(c) Haemophilia (d) Down syndrome
9. Thymine dimers are caused by
(a) X-Rays (b) Gamma rays
(c) alpha or beta particles (d) UV rays
10. A mutation that causes the change in one aminoacid with chemically similar amino
acid is known as
(a) Non-conservative mutation (b) Conservative mutation(c) Non-sense mutation (d) Silent mutation
III. Long Answer Type Questions
1. In your own words, explain what is mutation.
2. Describe the types of mutation and causes of mutations.
3. Explain the significance of mutations.
4. Explain that gene mutation occurs by substitution, deletion, inversion and insertion
of base pairs in DNA. Outline how such mutations may affect the phenotype.
5. Explain that the environment may affect the phenotype.
6. Outline the effects of mutant alleles on the phenotype in the following human
conditions: albinism, sickle cell anaemia, haemophilia and Huntington’s disease.
7. Explain the relationship between genes, enzymes and phenotypes with respect to the
gene for tyrosinase involved in the production of melanin.
8. Explain how a change in the base sequence of the gene for haemoglobin results in
abnormal haemoglobin and sickle-shaped red blood cells.
9. Distinguish between gene and chromosomal mutation.
10. Mutation plays a significant role in evolution. State the role. Also, evolution is the
biggest theory supporting environment sustenance. Guide the role of mutation indeveloping a sustained environment and continue the diversity in organisms.
REFERENCES
•Dr. B. S. Chauhan, Environmental Studies, University Science Press, New Delhi.
•Wilfred D. Stein, W. R. Lieb, Transport and Diffusion Across Cell Membranes, Academic Press Inc. (London) Ltd.
•Daniel L. Kaplan, The Initiation of DNA Replication in Eukaryotes, Springer International Publishing.
•Michael Robert, Michael Jonathan Reiss, Grace Monger; Advanced Biology, Nelson Publishers, UK.
•C. Ladd Prosser, Environmental and Metabolic Animal Physiology, Wiley-Liss Inc.
•Daniel D. Chiras, Human Biology, Jones and Bartlett Publisher, Sudbury.
•Beckett B. S. (1986). Biology A Modern Introduction. Oxford University Press, GCSE Edition.
•Kent, M (2000). Advanced Biology. A New Mainstreamtext for the New Specifications. Oxford University Press, New York.
•McKean DG (1984). Introduction to Biology. Third tropical edition.
•MINEDUC, Advanced Level Biology Curriculum. Kigali: NCDC.
•https://en.wikibooks.org/wiki/A-level_Biology/Biology_Foundation/nuclear_division
•http://www.biology-pages.info/D/Diffusion.html
• http://www.biology-pages.info/D/DNAReplication.html
•http://www.biotopics.co.uk/genes/dna.html
•http://www.biology-pages.info/C/Codons.html
•http://byjus.com/biology/photosynthesis-autotrophic-nutrition/
•http://www.livescience.com/26579-immune-system.html
•http://www.mcwdn.org/body/reproductive.html•http://www.youtube.com/watch? v=8mvkcH 15220
INDEX
