Gene mutations- Spontaneous and Induced

1. Gene mutations- Spontaneous and
Induced
Vaishali S.Patil
Assosiate Professor, Department of Botany
Shri Shivaji College of Arts, Commerce & Science
Akola

2. 1.Mutations are changes in the genetic sequence, and they are a main
cause of diversity among organisms.
2.Some mutations affect only the individual that carries them, while
others affect all of the carrier organism's offspring, and further
descendants.
3.It occur in cells that produce the next generation.
4.It affect the hereditary material.
5. It is a change that affects the nucleic acids, these nucleic acids are
the building blocks of DNA which(in viruses they are either DNA
or RNA ) are substances that carry the long-term memory of the
information required for an organism's reproduction.

3. 6.Mutations occur randomly with respect to whether their effects are
useful.
7.Mutations result from errors during DNA or viral replication, mitosis,
or meiosis or other types of damage to DNA (such as pyrimidine
dimers caused by exposure to ultraviolet radiation), which then may
undergo error-prone repair (especially microhomology-mediated end
joining), cause an error during other forms of repair, or cause an error
during replication (translesion synthesis).
Inheritance is based on genes that are faithfully transmitted from
generation to generation in microorganisms (in all organisms). Despite
the biochemical mechanisms that facilitate such transmissions faithfully,
sudden change in the sequence of nucleotide bases in genes can and
do occur. These changes called mutations, introduce variability into the
gene pool and are heritable. Therefore, a mutation can be defined as “a
sudden and heritable change in the nucleotide sequence of a gene”.
Mutations always change the genotype (the genetic constitution of
the cell ie. hereditary) and thus the phenotype (the expression of the
genotype in observable properties) of the microorganisms.

4. A microbial cell exhibiting change in its phenotype (observed properties
in morphology, development or behavior) in due to the effect of a
mutation is a mutant (mutant strain).
Any physical or chemical agent that increases the mutation-rate is
called mutagen or mutagenic agent.
Mutation is an important phenomenon because it is the ultimate
source of genetic variation and provides the raw material for
evolution.
All the genes would exist in only one form and no mutants (alleles)
would be produced without mutation.
Thus the mutations are essential to provide new genetic variability to
allow microorganisms to evolve and adapt to environmental changes.
At the same time, if mutations occurred too frequently they would
totally disrupt the transmission of genetic information from
generation to generation.

5. However, mutations occur only rarely in nature; a microbial
population typically contains about one in 108 cells that carries a
detectable mutation in any given gene. But, exposure of
microorganisms to certain powerful mutagens increases
dramatically the frequency of their mutant cells, by as much as 105-
fold.
Occurrence of Mutations:
Mutations occur in one of the two ways – spontaneous or induced.
(i) Spontaneous Mutations: Spontaneous mutations are those that
arise occasionally in the absence of a known cause, i.e., without
exposure to external agents. These mutations may result from errors in
DNA replication, or from the action of transposons, or even from the
effect of some mutagenic agents present in the environment.
Some most commonly operating spontaneous mutation mechanisms
are as follows:
1. Transition and Transversion Mutations (Errors in DNA
Replication):

6. The bases of nucleotides in DNA strands exist in tautomeric form, i.e.,
they exist as structural isomers that are in chemical equilibrium and
readily change into one another. Bases typically exist in keto form and
seldom they can take on either an imino or enol form by error
resulting in a rare tautomeric form (Fig. 29.9A).
These tautomeric shifts alter the hydrogen bonding characteristics of the
bases allowing purine for purine(A-G) or pyrimidine for pyrimidine
substitutions(C-T or U) which can eventually result in a stable
alteration of the nucleotide sequence (Fig. 29.9B).Such substitutions are
called transition mutations. In base pairing A-T and G-C.
In transversion mutation, a pyrimidine substitutes a purine or a
purine substitutes a pyrimidine. These mutations are rarer due to the
steric problems of pairing pyrimidine with pyrimidine and purine with
purine.

8. 2. Frame-Shift Mutations:
Spontaneous mutations also arise from frame-shifts, usually caused by
the deletion of DNA segments resulting in an altered codon reading
frame. It occurs where there is a short repeated nucleotide sequence.
In such a location, the pairing of template and its complementary strand
(new strand) can be displaced by the distance of the repeated sequence
leading to additions or deletions of bases in the complementary strand
(Fig. 29.10).
These spontaneous frame-shift mutations originate from lesions in DNA
as well as from replication errors. For example, it is possible for purine
nucleotides to be depurinated, i.e., to lose their base.
This results in the formation of an aprinic site, which will not base pair
normally and may cause a transition type mutation after the next round of
replication. Cytosine can be deaminated to uracil, which is then removed
to form an apyrimidinic site.

10. (ii) Induced Mutations:
Any agent which directly damages DNA, changes its chemistry, or
interferes with repairs mechanisms will induce mutations and the
agents which cause such actions are known as mutagens. They can be
conveniently classified according to their mechanism of action.
Following are the modes of mutagens actions:
1. Base Analogs :(molecular structure closely similar to that of
another)
These are similar to normal nitrogenous bases and can be incorporated
into the growing polynucleotide chain during replication. Once in place,
these compounds typically exhibit base pairing properties different from
the bases they replace and can eventually cause a stable mutation. 5-
bromouracil (5- BU), is a widely used base-analog of thymine (Fig.
29.11). It undergoes a tautomeric shift from the normal keto form to an
enol much more frequently than does a normal base.
The enol forms hydrogen bonds like cytosine and directs the
incorporation of guanine rather than adenine. The mechanism of action
of other base analogs is similar to that of 5-bromouracil.

12. 2. Specific Mispairing:
This action is caused when a mutagen changes a base’s structure and,
therefore, alters its base pairing characteristics. Certain mutagens in
this category are selective. They preferentially react with some bases and
produce a specific kind of DNA damage. Methyl- nitrosoguanidine an
alkylating agent that adds methyl groups to guanine, causing it to
mispair with thymine.
A subsequent round of replication could then result in a GC-AT
transition. Ethylmethane- sulfonate and hydroxylamine are other
examples of mutagens with similar mode of action.
3. Intercalating Agents: These agents distort DNA(give a misleading
or false account) to induce single nucleotide pair—insertions and
deletions. These mutagens are planar and insert themselves (intercalate)
between the stacked bases of the helix. This results in a mutation,
possibly through the formation of a loop in DNA. Acridines
(proflavin) and acridine orange are important intercalating agents.

13. 4. Other Mutagenes:
Several carcinogens directly damage DNA bases severely (hydrogen
bonding between base pairs is impaired or prevented and the damaged
DNA can no longer act as a template).
UV radiation generates cyclobutane type dimers (thymine dimers),
between adjacent primidines. Aflatoxin B1 and other benzo (a) pyrene
derivatives cause damage to DNA which is generally lethal but may
trigger a repair mechanism that restores much of the damaged genetic
material.
The Expression of Mutations:
The expression of a mutation can be observed if it produces a detectable,
altered phenotype. A mutation from the most prevalent gene form, the
wild type, to a mutant form is called a forward mutation.
Later, a second mutation may make the mutant appear to be a wild-
type organism again. Such a mutation is called a reversion mutation
or back mutation. In this the organism revertes back to its original
phenotype. A true mutation converts the mutant nucleotide sequence
back to the wild-type arrangement.

14. The wild-type phenotype also can be regained by a second mutation in a
different gene, a suppressor mutation, which overcomes the effect of the
first mutation. Sometimes, however, mutations may take place and do not
alter the phenotype for a variety of reasons. When a large deletion and
insertion mutations exist and affect only one base pair in a given
location, they are called point mutations.
Following are important types of point mutations:
1. Silent Mutation: It is the kind of point mutation that could not be
detected without use of nucleic acid sequencing techniques. If a
mutation is an alteration of the nucleotide sequence of DNA, mutations
can occur and have no visible effect because of code degeneracy. When
there is more than one codon for a given amino acid, a single base
substitution could result in the formation of a new codon for the same
amino acid.
For example, if the codon CGU were changed to CGC, it would still
code for arginine even though a mutation had occurred. The expression
of this mutation would not be detected except at the level of the DNA or
mRNA. Since there would be no change in the protein, there would be no

15. change in the phenotype of the organism.
2. Missense Mutation:
It is a second type of point mutation that involves a single base
substitution in the DNA that changes a codon for one amino acid into
a codon for another. For example, the codon GAG, which specifies
glutamic acid, could be changed to GUG, which codes for valine.
3. Nonsense Mutations:
It is a third type of point mutation and involves the early termination of
translation and therefore results in a shortened polypeptide. Such
mutations involve for conversion of a sense codon to a non-sense or
stop codon. Depending on the relative location of mutation, the
phenotypic expression may be more or less severely affected.
4. Frame-shift Mutation:
It is a fourth type of point mutation that arise from the insertion or
deletion of one or two base pairs within the coding region of the
gene. These mutations normally are very deleterious and yield mutant
phenotypes resulting from the synthesis of nonfunctional proteins (Fig.
29.12).