Mutation

Mutation is any hereditary change in the genetic makeup of an individual other than that which called by simple recombination of gene. These include changes in the gene structure or composition (gene mutation or point mutation) and the changes in the chromosome either in structure or in number (chromosomal mutation). But more frequently the term mutation is used only for gene mutation. The term mutation was introduced by Hugo. De Vries.

Gene Mutation

Since these mutations include very limited segment of DNA, these are called Point Mutation. It is classified into main 2 types

i.                 Substitution Mutation

ii.             Fram-shift Mutation

Substitution Mutation

In a substitution mutation a nitrogenous base of a tripled codon of DNA is replaced by another nitrogenous or some derivative of the nitrogen base and thus changing the codon.

It may results in the formation of another protein molecule. This type of substitution mutations are again classified into 4 types i.e. Transition and Transversion.

Transition is 4 types.

i.Taufomerization

ii.Ionization

iii.Base Analogoes

iv.Deamination

Transition

Transitions are changes that involve the replacement of one pairing by another pairing and correspondingly in the complementary chain the replacement of one Pyrimidin by another Pyrimidin.

DNA     =>   TAC CAT TAG GAG CCC ATT

m- RNA => AUG GUA AUC CUC GGG UAA

   (Starting codon)(Valine)(Isolucine)(Lucine)(Glycine)(Termination codon)

                                             

DNA     => TAC CAT TGG GAG CCC ATT

m- RNA=> AUG GUA ACC CUC CGG UAA

                                             Valine Threonine Leucine Glycine

The transitional Substitution can be introduced by any of the following 4 ways like

(a)Tautomerization

(b)Ionization

(c)Base Analoges

(d)Deamination

Tautomerization

In a normal DNA molecule the Adenine linked to Thymine by 2 bonds while Guanine is linked to Cytosine by 3 Bonds. However sometimes these 4 nitrogenous bases exist in alternate states and these states are called Tautomers. Thus, the rearrangement in the distribution of Hydrogen atom is called Tautomeric Shift due to Tautomerization the amino group (NH2) of Cytosine and Adenine is converted into NH group (Imino group) and similar the keto group (C=O) of Thymine and Guanine is converted to anol group (OH group).

Thus, in a Tautomeric state the nitrogenous base cannot pair to its normal partner rather a tautomeric Adenine pair with normal Cytosine and tautomeric Guanine Pairs with normal Thymine. Such pair of Nitrogenous base are known as unusual base pair or forbidden base pair. Finally such tautomeric bases introduced Mutation during DNA Replication. But this type of situation not a stable one because at the next replication the tautomeric base returns to common base again.

Ionization

Transition may also be introduced by Ionization of a base at the time of DNA replication. Ionization involved the loss of hydrogen from number 1 nitrogen of a nitrogenous base.

Example- In its ionized state Thymine pairs with normal Guanine and Ionized Guanine links with normal Thymine.

Base Analogous

They occur as natural as well as artificial base analogous some of the natural base analogos are-

5Methyl Cytosine, 5- Glycosyl Hydroxyl Methyl Cytosine, 5-Hydroxy Methyl Uracil, 6- Methyl Purine

The artificial base analogos are:- 5 Bromo Uracil,5 iodo Uracil and 5 Methyl Cytosine.

Deamination

Certain chemical substances like nitrous acid (HNO2), Diethyl Sulphate (DES), Ethyl ethane sulphate (EES), NitrosoMethyl Urea(NMV) etc change the base sequence in DNA by a series of chemical step. Generally they cause deamination of nitrogenous base by replacing amino group (-NH2) by Hydroxy group (-OH). Hence the Deamination of Cytosine leads to the formation of Uracil Deamination of Adenine forms hypoxanthine and deamination of Guanine leads to the formation of Xanthine.

Transversion

Replacement of purine by a Pyrimidine or viceversa is known as transversion and it is called by de- either alkylating agent like Ethyl Methane Sulphate(EMS) and Methyl Methane Sulphate(MMS) include substituent by two ways-

(a)           By substituting a purine for purine or substituting Pyrimidine for a Pyrimidine(Transition)

(b)          By substituting a purine for pyrimidine or substituting pyrimidine for purine

For causing transversion these alkilating agent alkilate the purine bases in the nitrogen at the 7^th position in the Guanine and Adenine and finally leads to its separation from the DNA strand this is known as depurination.

Frame- Shift Mutation

The Mutation caused by the addition or deletion of nitrogenous bases in DNA or m-RNA are known as Frame- Shift Mutation. Here one deletion may be neutralized by addition or viceversa provided they occur at the same place.

Frame- Shift Mutations are of 2 types.

(i)Deletion mutation:

The Mutations are caused due to loss or deletion of one or more nucleotide.

(ii)Insention mutation:

These mutations are caused by the addition of one or more nucleotides in a DNA molecule at one or more places.

DNA    => TAC CAT TAG GAG CCC ATT

m- RNA=> AUG GUA AUC CUC GGG UAA

  (Start codon) (Valine) (Isoleucine) (Leucine) (Glycine) (Termination codon)

DNA => TAC CCA TTA GGA GCC CAT     TAC CAT AGG AGC CCA

                AUG GGU AAU CCU CGG GUA AUG GUA UCC UAG GGU

Chromosomal aberration

Each and every kind of Plant and animal is characterized by a fixed set of chromosome. During mitotic cell division chromosomes are transmitted intact but some time irregularly during cell division produce visible structural changes in one or more chromosomes such morphological abnormalities in chromosome are called chromosomal aberrations. It usually refers to changes in parts of individual chromosome but not whole set of chromosome.

It is of two types-

(A) Changes involving the no. of gene loci. It is of two types

i.Deficiency or deletion

ii.Duplication

(B) Changes involving the arrangement of gene loci. It is two types

iii.Translocation

iv.inversion

Deficiency or Deletion

Deficiency means loss of chromosomal segments which results in the loss of one gene or a group of gene. The segment of chromosome which separate from the main chromosome lacks a centromere and it doesn’t survive. It results in the loss of genetic material. The reason for such loss of chromosomal segment may be chemicals, drugs, viral infection, radiation or high temperature. Deletion is 2 types

 (i) Terminal Deletion

(ii)Intercalary Deletion

Terminal Deletion

(Picture)

It refers to the loss of a segment from one end of the chromosome. Here a single break separates the terminal part and that deleted part is unable to survive as if lack a centrosome.

Intercalary Deletion

(Picture)

It involves the loss of an intercalary segment of the chromosome with the reunion of terminal segments. Thus, the chromosomes break at two parts with the loss of a segment. At the same time the other homologous chromosome bends its half to form a loop.

Although deficiency and deletion are synonymous but a distinction is often made, the loss of terminal segment of the chromosome is often described as deficiency where as the loss in intermediary position is designated by deletion. The consequence of deletion depends on the loss of the genetic material. Normally a deletion has harmful effect on organisms. If the amount of quality of gene loss is minimum, it has little effect on the organisms. However loss of a plug of genes may produce lethal mutant character.

In human baby deletion of a segment of chromosome number 5 causes a disease called cri-du-chat syndrome. In this case the baby cry like a cat and it is mentally retarded with small head.

Duplication

When a part of the chromosome is repeated in the same chromosome it is called Duplication. It means the presence of same block of genes more than one is known as Duplication. Duplication not many arises due to unequal crossing over between chromosomal segments. Thus, a group of gene deleted from one chromosome may be joint to another chromosome. So the chromosome configuration is emerged. Depending upon the arrangement of duplicated gene on the chromosome duplication can be classified in 3 types.

i.Tendem Duplication

ii.Reverse Duplication

iii.Displace Duplication

(Picture)

 (i)Tendem Duplication

In Tendem duplication the added segment have same genetic sequence present as present in original state in chromosome. More over the added segment lies in close association with original segment.

ii.Reverse Tendem

In such a duplication the sequence of gene attached to the chromosome piece is just the reverse of the tendem variety.

iii.Displace

In this case the chromosomal segment gets attached to some non- homologous chromosome.

Duplication is more frequent but less harmful than other chromosomal abnormalities. But in some cases the addition of duplicated gene may contain lethal mutant. An example of duplication in Drosophila is bar character of eye.

Depending upon which part of non homologous chromosome become detached and reunited translocation can be of 3 types

i.Simple Translocation

ii.Shift Translocation

iii.Reciprocal Translocation

(Picture)

Simple Translocation

In this case the chromosome break only at one point so, that broken segment is added to the end of other non- homologous chromosome. This type of Translocation is very rare in nature.

Shift Translocation

In this case the intestinal segment of one chromosome is broken off and inserted within the break of another non homologous chromosome. Thus, shift translocation involves break at three point two in one chromosome and one in other non homologous chromosome.

Reciprocal Translocation

In this case each one of the two chromosome break at one point and three exchange of chromosomal segments.

In some cases multiple translocations occur between more than two pairs of non homologous chromosome. It has been studied in Drosophila.

Translocations are of common occurrence and they play important role in the introduction of genetic polymorphism in the population and origin of new species. Human being translocation between 15^th and 21th chromosome causes Down ’s syndrome.

Inversion

It is a kind of chromosomal aberration in which the chromosome break into two segment and the detected segment again join to the original chromosome but in a reverse order.

A B C {D E F } G H        A B C F E D G H

Thus the numbers of genes remain unchanged but the sequence is altered by the rotation of a block of a gene in the chromosome.

Inversions are of two types. Such as Paracentric and Pericentric

(Picture)

i.Paracentric

When the breaks in the chromosome during inversion occur on the one side of the centromere the inversion is known as Paracentric. Thus, the inverted segment of chromosome is without centromere. If such inversion occur singly it is known as homobranchial inversion but when the paracentric inversion occurs one on either side of the centromere it is known as inter radial or branchial inversion.

ii.Pericentric

In this inversion there is the involvement of centromere i.e. it involve one break at either side of the centremere. As a result of which sub metacentric chromosome is converted to Metacentric chromosome.

Inversion generally provides proof for the occurance of the crossing over and thus, it helps in origin of new species and it has a great significance in evolution.

Chromosomal aberration according to variation in chromosome number-

Every organism has a fixed number of chromosomes during gametogenesis. This number is reduced to half. Thus, the basis set of chromosome in the gamete is called haploid set and in the somatic cell it is called diploid set. But sometimes irregularity occurs either during cell division or during fertilization. This results in the production of variable cell where the chromosome number does not remain constant such a variation in the number of chromosome is called Heteroploidy. It is of two types

i.Aneuploidy

ii.Euploidy

i.Aneuploidy

Aneuploidy is a chromosomal aberration where there is a gain or loss of one or more chromosome within a single set. It is caused by the process called non disjunction during meiosis. It is three types.

A.Monosomy

B.Nullisomy

C.Trisomy

Monosomy

It is a chromosomal aberration where one chromosome is lost from a pair. Thus, it is represented by (2n-1). In that way a monosomic Drosophila has (8-1)= 7 chromosome and a monosomic man has 45 chromosome. Such monosomic condition in man causes a syndrome called Turner’s syndrome, where the genotype of that individual becomes 44A + XO.

Nullisomy

In this type of aberration both the chromosomes of a pair are lost. Thus it represented by (2n-2) and the genotype becomes 44A + OO and such individual can’t survive.

Trisomy

It is a chromosomal aberration where one chromosome is added to a pair so, it is represented by (2n + 1) in that way a trisomoc man has 46 + 1= 47 chromosome. 

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