Course: B.Sc Life Sciences, IVth SEM

Paper: Genetics and Evolutionary Biology

Date: 17/03/2020

Topic: Mutations (Theory)

Teacher: Dr Ritu Rai (Department of Zoology)

Unit 4: Mutations

Chromosomal Mutations: Deletion, Duplication, Inversion, Translocation, Aneuploidy and Polyploidy;

Gene mutations: Induced versus Spontaneous mutations, Back versus Suppressor mutations

Chromosomal mutation was already discussed in class on 3rd March, 2020.

GENE MUTATIONS

A change in the sequence of bases in DNA is called a mutation. Most people have

dozens of mutations in their DNA. Mutations are essential for evolution to occur.

Although most mutations have no effect on the organisms in which they occur, some

mutations are beneficial whereas others are harmful mutations.

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TYPES OF GENE MUTATIONS

I On the basis of location:

Somatic Mutation: If a mutation happens to occur in a somatic cell (in multicellular

organisms), it is called as somatic mutation. The mutant characteristic affects only

the individual in which the mutation occurs and is not passed on to the succeeding

generation

Germline Mutation: A mutation in the germ line of sexually reproducing organisms

is called a germ-line mutation. It may be transmitted by the gametes to the next

generation, producing an individual with the mutation in both its somatic and its

germ-line cells.

II Based on type of molecular change:

A Point mutation: change of one base pair

Point mutations fall into two general categories: base-pair substitutions and base-

pair insertions or deletions.

i) Base pair substitution mutations: A base-pair substitution mutation is a

change from one base pair to another in DNA, and there are two general

types:

Transition and Transversion

A transition mutation is a mutation from one purine–pyrimidine base pair to the

other purine–pyrimidine base pair, such as A–T to G–C. Specifically, this means that

the purine on one strand of the DNA (A in the example) is changed to the other

purine, while the pyrimidine on the complementary strand (T, the base paired to the

A) is changed to the other pyrimidine.

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A transversion mutation is a mutation from a purine–pyrimidine base pair to a

pyrimidine–purine base pair, such as G–C to C–G, or A–T to C–G. Specifically, this

means that the purine on one strand of the DNA (A in the second example) is

changed to a pyrimidine (C in this example), while the pyrimidine on the

complementary strand (T, the base paired to the A) is changed to the purine that

base pairs with the altered pyrimidine (G in this example).

Base-pair substitutions in protein-coding genes also are defined according to their

effects on amino acid sequences in proteins. Depending on how a base-pair

substitution is translated via the genetic code, the mutations can result in no change

to the protein, an insignificant change, or a noticeable change. The various types

are:

a) Missense Mutation: A missense mutation is a gene mutation in which a

base-pair change causes a change in an mRNA codon so that a different

amino acid is inserted into the polypeptide. A phenotypic change may or may

not result, depending on the amino acid change involved.

b) Nonsense Mutations: A nonsense mutation is a gene mutation in which a

base-pair change alters an mRNA codon for an amino acid to a stop

(nonsense) codon (UAG, UAA, or UGA). A nonsense mutation causes

premature termination of polypeptide chain synthesis, so shorter-than normal

polypeptide fragments (often nonfunctional) are released from the ribosomes.

c) Neutral Mutations: A neutral mutation is a base-pair change in a gene that

changes a codon in the mRNA such that the resulting amino acid substitution

produces no detectable change in the function of the protein translated from

that message. A neutral mutation is a subset of missense mutations in which

the new codon codes for a different amino acid that is chemically equivalent to

the original or the amino acid is not functionally important and therefore does

not affect the protein’s function. Consequently, the phenotype does not

change

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d) Silent Mutation: A silent mutation also known as a synonymous mutation—is

a mutation that changes a base pair in a gene, but the altered codon in the

mRNA specifies the same amino acid in the protein. In this case, the protein

obviously has a wild-type function. Silent mutations most often occur by

changes such as this at the third—wobble—position of a codon. This makes

sense from the degeneracy patterns of the genetic code.

ii) Frameshift Mutations:

If one or more base pairs are added to or deleted from a protein-coding gene, the

reading frame of an mRNA can change downstream of the mutation. An addition or

deletion of one base pair, for example, shifts the mRNA’s downstream reading frame

by one base so that incorrect amino acids are added to the polypeptide chain after

the mutation site. This type of mutation, called a frameshift mutation, usually results

in a non-functional protein. Frameshift mutations may generate new stop codons,

resulting in a shortened polypeptide; they may result in longer-than-normal proteins

because the normal stop codon is now in a different reading frame; or they may

result in a significant alteration of the amino acid sequence of a polypeptide. In

Figure, an insertion of a G–C base pair scrambles the message after the codon

specifying glutamine. Since each codon consists of three bases, a frameshift

mutation is produced by the insertion or deletion of any number of base pairs in the

DNA that is not divisible by three.

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Fig. Types of Point Mutations

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III On the basis of phenotypic effect:

Point mutations are divided into two classes, based on how they affect the

phenotype:

A forward mutation changes a wildtype gene to a mutant gene

A reverse mutation (also known as a reversion or back mutation) changes a

mutant gene at the same site so that it functions in a completely wild-type or nearly

wild-type way. Reversion of a nonsense mutation, for instance, occurs when a base-

pair change results in a change of the mRNA nonsense codon to a codon for an

amino acid. Back mutation is a type of reverse mutation, restoring the original DNA

sequence. Generally, it is a second mutation, which follows the starting mutation.

However, the second mutation occurs at the point where the starting mutation exists.

Therefore, it can restore the original DNA sequence of the gene. As a result, the

original phenotype of the organism or the wild type can be seen in the revertant.

Thus, the back mutation is a type of true reverse mutation.

For example, when a wild type sequence contains GC bases at a particular site, the

mutant or the organism with the starting mutation may have AT in the same position.

However, this AT can be reversed in a back mutation into GC, which in turn restores

the original gene sequence as well as the phenotype in the revertant. 

If this reversion is back to the wild-type amino acid, the mutation is a true reversion.

If the reversion is to some other amino acid, the mutation is a partial reversion, and

complete or partial function may be restored, depending on the change. Reversion of

missense mutations occurs in the same way.

The effects of a mutation may be diminished or abolished by a suppressor mutation—a mutation at a different site from that of the original mutation. Suppressor mutation is the second type of reverse mutation. However, it is not a type of a true reverse mutation. Therefore, it may not restore the original DNA sequence, leading to the true wild type. Furthermore, the site of the second mutation is different from the site of the starting mutation. Therefore, the functional products of both types of suppressor mutations carry the starting or primary mutation A suppressor mutation masks or compensates for the effects of

the initial mutation, but it does not reverse the original mutation. Suppressor

mutations may occur within the same gene where the original mutations occurred,

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but at a different site (in which case they are known as intragenic suppressors), or

they may occur in a different gene (where they are called intergenic suppressors).

Both intragenic and intergenic suppressors operate to decrease or eliminate the

deleterious effects of the original mutation. However, the mechanisms of the two

suppressors are completely different. Intragenic suppressors act by altering a

different nucleotide in the same codon where the original mutation occurred or by

altering a nucleotide in a different codon. An example of the latter is the suppression

of a base-pair addition frameshift mutation by a nearby base-pair deletion. Intergenic

suppression is the result of a second mutation in another gene. Genes that cause

the suppression of mutations in other genes are called suppressor genes. For

example, in the case of nonsense suppressors, particular tRNA genes mutate so that

their anticodons recognize a chain-terminating codon and put an amino acid into the

chain. Thus, instead of polypeptide chain synthesis being stopped prematurely

because of a nonsense mutation, the altered (suppressor) tRNA inserts an amino

acid at that position, and full or partial function of the polypeptide is restored. This

suppression process is not very efficient, but sufficient functional polypeptides are

produced to reverse or partially reverse the phenotype.

Fig. t-RNA suppressor gene mechanism

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What is the Difference Between Back Mutation and Suppressor Mutation?

The main difference between back mutation and suppressor mutation is that back

mutation is a point mutation which restores the original sequence whereas

suppressor mutation is a second mutation which either alleviates or reverts the

phenotypic effects of an already existing mutation. Furthermore, back mutation

restores the true wild type; suppressor mutation only masks the effect of the first

mutation while the gene holds the first mutation. In addition to these, the two types of

suppressor mutations include intragenic and intergenic/extragenic mutations.  

Back mutation and suppressor mutation are two types of reverse mutations, which

are second mutations following a particular mutation event. Significantly, they revert

the effect of the existing mutation and restores the original phenotype. 

What are the Similarities Between Back Mutation and Suppressor Mutation?

Back mutation and suppressor mutation are types of secondary mutations.

Both affect the primary mutation directly.

Both functions to reverse the effect of the primary mutation.

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