These mutations are caused by a change in the nucleotide type and sequence of a DNA segment representing a gene.The first recorded gene mutations are Ancon Sheep and hornless ( polled) cattle. The first scientific study of gene mutations started with the discovery of white eye trait in Drosophilia by Morgan. All genes have potential to undergo mutations but it differs from gene to gene. Mutations can occur in every conceivable direction and to every conceivable degree. Mutations can occur in both somatic and germinal cells. Mutations may be lethal, harmful, neutral or advantageous. Most of the mutations are recessive and harmful. Mutator genes increase the rate of mutation in some genes while antimutator genes reduce the frequency of mutation of certain genes.

Reverse Mutations:

Most mutant events consist of a change from wild or normal type to a new mutant genotype. Such mutation events are known as forward mutations,  in contrast to the back or reverse mutations, in which the mutant genotype changes back to the wild type.

Spontaneous and Induced Mutations:

1): Spontaneous Mutations:

They occur randomly and automatically in nature. The possible reasons are:

(i) Background Radiations: They are present in natural surroundings and come from various sources, e.g., sun, radioactive minerals. 

(ii) Tautomers: All the four nitrogen bases also occur in their tautomeric or isomeric states, forming either imino group ( __NH, e.g., cytosine, adenine) instead of amino group ( __ NH2) or enol group ( __ COH, e.g. thymine, guanine) instead of keto group ( =CO). Tautomers pair with different bases so as to cause a change in the sequence like AT to CG. 

(iii)Deamination of Cytosin : Cytosine slowly dominates to produce uracil which pairs with adenine resulting in change in base pairing and thus causing mutation. 

(vi) Copy Error: Many steps are  involved in replication, transcription and translation. Any wrong choice or entry of different group will result in mutation. Most of these errors are rectified  during proof reading but a few may escape this rectification and thus will cause mutations. 

2): Induced Mutations:

They are mutations that are produced artificially will the help of certain agents called mutagens.


Any extracellular physical or chemical factor that has the ability to cause mutations or increase the frequency of mutations is called mutagen.

1): Physical Mutagens:

They are of two types, temperature and high energy radiations. 

(i) Temperature:Rise in temperature increases the rate of mutations with Q10= 5. Increased temperature breaks the hydrogen bonds between the two strands of DNA and denatures it. It disturbs the synthetic process connected with replication and transcription. In Rice, low temperature increases the rate of mutations. 

(ii) High Energy Radiations:The biological effect of different radiations is not equally harmful. The harmful effect is determined by the penetration and ionizing power of the rays. Radiations are broadly divided into two categories:

( a) Ionizing radiations: These include X_ rays, alpha rays, neutrons and protons. Alpha and beta rays do not penetrate beyond the human skin and, therefore, usually do not affect internal body cells. The gamma rays and X_ rays collide with the biomolecules at high speed and eject electrons from the outer shells of atoms. These atoms after losing electrons, become positively charged ions. The ejected electrons after losing their energy, get attached to other atoms which then become negatively charged ions. These ions undergo chemical reactions to neutralize their charge to reach a stable state. During these reactions, the mutagenic effects of ionizing radiations are produced. The ionizing radiations produce breaks in the chromosomes. These breaks then lead to loss of chromosomes, chromosome segments, deficiencies, duplication, translocations or inversions.

X_ rays are known to dominate and dehydroxylate nitrogen bases, form peroxides and oxidize deoxyribose. Muller was the first to induce mutations in Drosphila with the help of the X _ rays.

(b) Non_ ionizing radiations: These radiations which include ultraviolet rays, have longer wave lengths and carry much lower energy. Their penetration power is,therefore, much less than the ionizing radiations. In human beings, UV rays are usually absorbed by the skin and the gonads remains unaffected. 

The UV rays  may be absorbed by the nucleic acids. Two adjacent Pyrimidines of the same DNA strand form covalent bonds forming dimers. The thymine dimer is formed most frequently. Dimerization interferes with the proper base pairing of thymine with adenine and may result in the pairing of thymine with guanine. 

 2)  Chemical Mutagens:

They are of several types: The common ones are nitrous acid, alkylating agents, base analogues and acridines.

(i) Nitrous Acid: Discussed under transitions.

ii) Alkylating Agents:Nitrogen mustards, diethyl sulphate ( DES), dimethyl nitrosamine ( DMN) and other alkylating agents cause methylation or ethylation of nitrogen bases. The abnormal bases fail to pair with normal partners and also prevent separation of two DNA strands.

(iii) Base Analogues:Discussed under transitions.

(vi) Acridines: Discussed under frame shift mutations. 

What are the four types of gene Mutations ?

Mechanism of Gene Mutations:

The smallest part of a gene that can undergo mutation is known as muton.Muton can be as small as a single nucleotide. These gene involving a change in only a single nucleotide or nitrogen base are called point mutations. Sickle cell anaemia is a classical example of point mutation. A mutation involving more than one base pair is known as a gross mutation. Gene mutations usually occur during replication of DNA. These are, therefore, also called copy error mutations. A gene may undergo many point mutations. This results in formation of multiple alleles. Gene mutations occur by three methods _ inversion, substitution and frame shift.

1): Inversion:Distortion of DNA because of mutation can change the base sequence of  cistron in the reverse order.The process is called inversion. The new sequence will possess different codons which may code for different amino acids,e.g.,

2): Substitution ( Replacement):In substitution a nitrogen base is changed with another. It is further of two types, transition and transversion.

(a) Transition : In this case a nitrogen base is replaced by another of its type, that is, one purine is replaced by another purine ( adenine šŸ”guanine) or one pyrimidine is replaced by another pyrimidine ( cytosinešŸ”thymine or uracil).The transition can be introduced by any of the following ways:

(i) Tautomerisation: As already explained, tautomeric form of a nitrogenous base does not pair with its normal partner. A tautomeric purine adenine pairs with the normal cytosine ( instead of guanine) and tautomeric guanine pairs with thymine ( instead of cytosine).Similarly, tautomeric thymine pairs with normal guanine and cytosine with adenine. Such pairs of nitrogenous bases are known as 'forbidden base pairs ' or 'unusual  base pairs'. These rare bases can introduce mutations during DNA replication. 

For example, if adenine in part DNA is in rare state, the complementary new chain formed from this chain would possess cytosine. At the time of next replication, this cytosine would pair with guanine.  This will result in substitution of A= T base pair by G= C base pair. Similarly,  a substitution of G= C by A= T pair can be produced if cytosine is in tautomeric state.

( ii)Ionization: Transition may also be introduced by ionization of nitrogenous bases at the time of DNA replication. Ionsization of bases also results in faulty base pairing,  e.g., ionized thymine pairs with normal guanine ( instead of adenine) and ionized guanine pairs with normal thymine ( instead of cytosine).

(iii) Base Analogues: These are the compounds having molecular structure similar to the nitrogenous bases. The common base analogues are 5_ bromouracil, 5_ fluorouracil, 5_ methyl_ cytosine and 5_ lodouacil.

5_ Bromouracil ( 5_ BU) is  a structural analogue  of  tthymine.It cells grow in a medium containing 5_ BU, it is incorporated into newly replicated chain of DNA in place of thymine .5_ BU will pair up with guanine and when DNA undergoes further replication, G pairs with C. Thus A = T base pair is replaced by G= C base pair.

(vi) Deamination: Certain chemical substances like nitrous acid and hydroxyl a hydroxylamine, change the base sequence in DNA by a series of steps. Nitrous acid causes deamination of nitrogenous bases by replacing amino group  by hydroxyl group. The delamination of cytosine leads to formation of uracil, deamination of adenine leads to formation of hypoxanthine ( H) and that of guanine forms xanthine (X). Hypoxanthine mispairs with cytosine  and therefore, A= T will be replaced by G= C. Uracil will pair with adenine and thus G= C will be replaced by A= T

(b) Transversion: In this mutation a purine base is substituted by a pyrimidine base and vice versa, e.g., thymine with adenine and cytosine with guanine. 

3) Frame_ Shift or Gibberish Mutation:In  this case the reading of the frame of base sequence shifts laterally either in the forward direction due to insertion of one or more nucleotides or in the backward direction due to deletion of one or more nucleotides. Therefore, frame_ shift mutations are of two kinds, insertion and deletion. 

( a) Insertion: One or more nucleotides are added in the segment of DNA representing a cistron or gene.

(b) Deletion: One or more nucleotides are lost from a segment of DNA representing a cistron or gene.

Sometimes there is one insertion and one deletion of equal number  of nucleotides so that the frame does not move but mutation occurs due to change in one or more codons. Three deletions or three additions may disturb only a few frames.

Follwing Simple Example 

Consider a statement that is made up of the following words each having three litters like genetic code.

RAM       HAS         RED      CAP

If we insert a letter B in between HAS and RED  and rearrange the statement, it would read as follows:

RAM        HAS   BRC     DCP    P

Similarly, if we now insert two letters at the same place, say BI'. Now it would read.


Now we insert three letters together, say BIG, the statement would read 


The same exercise can be repeated, by deleting the letters R, E and D, one by one and rearranging the statement to make a triplet word.




Which type of  mutation is most harmful?

Mechanism of Origin of Fram_ shift Mutations:

According dyes are known to causes deletion or insertion of a single base pair .Acridines are tar derived hetero aromatic compounds from which a number of dyes and pharmaceuticals are prepared. Acridines ( e.g. acriflavine, proflavin, 5 amino acridine) enter the DNA chains in between two base pairs and thus increase the distance between them. At the time of replication, either a base pair is introduced in the gap or a base pair is lost. The frame of nucleotide sequence of DNA is disturbed and is read differently. 

Nonsense,Same _ sense and Mis_ sense Mutations: A nonsense  mutation stops protein synthesis due to formation of a termination or nonsense codon  in place of a normal codon, e.g., ATT( UAA), ATC ( UAG), ACT( UAG,). A mis_ sense mutation involves change in a codon that produces a different amino acid at the specific site in polypeptide, often resulting in the non_ functioning of polypeptide chain. A same _ sense mutation is silent mutation in which the  coden is changed but the change does not result in alteration of amino acid specificity (e.g., GCA➡️GCT or GCC or GCG).

tRNA _ the Adapter Molecule:

From the very beginning of the proposition of code, it was clear to Francis Crick that there had to be a mechanism to read the code and also to link it to the amino acids,  because amino acids have no structural specialities  to read the code uniquely. He postulatedthe presence of an adapter molecule that would on one hand read the code and on other hand would bind to specific amino acids. The tRNA, then called sRNA ( Soluble RNA), was known before the genetic code was postulated. However, its role as an adapter molecule was assigned much later.

tRNS has  an anticodon loop that has bases complementary to the  code, and it also has an amino acid acceptor end to which it binds to amino acids.  tRNA are specific for each amino acid and. For initiation,  there is another specific tRNA that is referred to as initiator tRNA .There are no tRNAs for stop codons .The secondary structure of tRNA has been depicted that look like  a clover _ leaf. In actual structure, the tRNA is a compact molecule which looks like inverted L.

What are examples of gene mutations?

There are numerous examples of gene mutations. Here are some common types and associated examples:

1: Point mutations:
   - Missense mutation: A single nucleotide change results in a different amino acid being incorporated into the protein. For instance, a mutation in the BRCA1 gene is associated with an increased risk of breast cancer.
   - Nonsense mutation: A single nucleotide change introduces a premature stop codon, leading to a truncated and non-functional protein. Cystic fibrosis, caused by mutations in the CFTR gene, often involves nonsense mutations.
   - Silent mutation: A mutation that does not cause any change in the amino acid sequence. It occurs when a nucleotide change in the DNA sequence does not affect the protein coding due to the degeneracy of the genetic code.

2): Frameshift mutations: 
   - Insertion and deletion mutations: Addition or removal of nucleotide(s), which changes the reading frame of the protein coding sequence. For example, Huntington's disease is caused by a CAG trinucleotide repeat expansion in the HTT gene.
3): Chromosomal alterations:
  ☆ Deletion: Loss of part of a chromosome. The cri-du-chat syndrome is caused by a deletion in the short arm of chromosome 5.
 ☆ Duplication: The presence of an extra copy of a chromosomal region. Duplication of the amyloid precursor protein (APP) gene is associated with an increased risk of Alzheimer's disease.
  ☆Translocation: The rearrangement of genetic material between non-homologous chromosomes. The Philadelphia chromosome, formed by a translocation between chromosomes 9 and 22, is linked to chronic myeloid leukemia (CML).
  ☆ Inversion: A segment of a chromosome breaks off and reattaches in the reverse orientation. Inversion mutations in the X chromosome can cause hemophilia A.
 ☆ Ring chromosome: When both ends of a chromosome are reunited, forming a ring structure. A ring chromosome 22 is observed in individuals with ring chromosome 22 syndrome.

It is important to note that these are just a few examples, and gene mutations can occur in various ways, resulting in a wide range of genetic disorders and diseases.

Why is a gene Mutation important?

A gene mutation is important because it can lead to changes in the genetic code, which can have a significant impact on the structure, function, and regulation of proteins. These changes can then affect various biological processes, leading to the development of genetic disorders, diseases, or altered traits. Here are some reasons why gene mutations are important:

1):Genetic Diversity:Gene mutations are a key driver of genetic diversity within a population. Mutations introduce new genetic variations that can be beneficial, neutral, or harmful. This diversity provides the raw material for natural selection and adaptation to changing environments.

2): Evolution:Gene mutations play a vital role in the process of evolution. Accumulation of mutations over time leads to the creation of new genetic traits and the selection of individuals with advantageous traits. This allows species to adapt and survive in different environments.

 3):Genetic Disorders and Diseases: Mutations can cause or contribute to the development of various genetic disorders and diseases. For example, mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of hereditary breast and ovarian cancer. Understanding these mutations is crucial for diagnosis, treatment, and prevention of genetic diseases.

4):Understanding Biology:Gene mutations provide insights into biological processes and molecular mechanisms. Studying mutations and their effects helps scientists understand gene function, protein interactions, and the regulation of genetic pathways. This knowledge is vital for advancing biomedical research and developing targeted therapies.

5): Pharmacogenomics:Gene mutations can influence an individual's response to medications. Variations in drug-metabolizing enzymes or drug targets due to gene mutations can affect the efficacy and safety of certain drugs. Understanding these mutations can improve personalized medicine approaches and lead to more effective drug treatments.

6):Forensics and Paternity Testing:Genetic mutations, particularly in non-coding regions of the genome, can be used in forensic DNA analysis and paternity testing. These mutations act as unique genetic markers that can help identify individuals, establish biological relationships, or determine genetic ancestry.

In summary, gene mutations are important because they contribute to genetic diversity, play a role in evolution, can cause genetic disorders and diseases, provide insights into biological processes, influence drug responses, and aid in forensic and paternity testing.

Biological significance of Point Mutations: Transition and transversios are relatively benign as they cause replacement of one amino acid in the polypeptide, which may not cause any significant effect. However frame shift mutations causes all the DNA beyond the point of mutation to be misread. Such mutations are often ethal.


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