Molecular Basis Of Mutation: Mutation, Repair and Recombination

Edited By Irshad Anwar | Updated on Jul 02, 2025 06:16 PM IST

The molecular mechanism of mutation consists of the alteration of the sequence of DNA, which can transform gene function or expression. They occur spontaneously during DNA replication by errors committed by DNA polymerase or tautomeric transitions of nucleotide bases. Despite proof-reading capabilities, approximately 1 in 10⁷ base pairs might suffer permanent alteration. Such spontaneous mutation is an important source of genetic variation and is responsible for driving evolution. But some can cause deleterious consequences, like genetic diseases.

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What is the Molecular Basis of Mutation?
What Is Gene Mutation?
Mutation and Its Types
Causes of Mutations And Their Types
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Molecular Basis Of Mutation: Mutation, Repair and Recombination

Induced mutations happen when DNA is subjected to an external mutagen, like UV radiation, X-rays, chemicals, or biological agents. For example, UV radiation induces thymine dimers, and alkylating agents mispair bases in DNA. Biological agents like viruses could integrate themselves into the genome of the host, disturbing gene function. These mutations could lead to disorders like cancer or inherited diseases.

What is the Molecular Basis of Mutation?

The molecular basis of mutation is changes in the nucleotide sequence of DNA, manifested in alterations of the genetic information it carries. These can be caused by spontaneous errors during DNA replication, by chemicals, radiation, and also by viruses. The results of mutations can be innocuous or injurious and can moreover influence the attributes of an organism, thus attaining genetic diversity in populations or genetic disorders.

What Is Gene Mutation?

A gene mutation is a permanent alteration within the DNA sequence that makes up the gene. Such mutations can happen in several ways, such as substitutions, insertions, deletions, and frameshift mutations. These changes can perturb gene function in a way that the expression of either a nonfunctional gene occurs or its production. Gene mutations are either inherited or acquired during an organism's lifetime and may make important contributions to a variety of diseases and evolutionary processes.

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Mutation and Its Types

Mutations can be classified according to the nature of the change in the DNA sequence. All 4 types of mutation, along with their comparison, are discussed below in the table:

Feature	Substitution (Transition & Transversion)	Insertion	Deletion	Frameshift Mutation
Definition	Another replaces one nucleotide	One or more nucleotides are added	One or more nucleotides are removed	Shifts the reading frame due to the insertion or deletion of nucleotides
Sub-types	Transition (purine↔purine, pyrimidine↔pyrimidine); Transversion (purine↔pyrimidine)	Not applicable	Not applicable	Not applicable
Effect on Reading Frame	No	Yes, if insertion is not in multiples of 3	Yes, if deletion is not in multiples of 3	Yes
Impact on Protein Sequence	May be silent (no change), missense (amino acid change), or nonsense (stop codon)	Alters the amino acid sequence, can introduce a frameshift	Alters amino acid sequence, can introduce a frameshift	Alters the entire downstream amino acid sequence
Possibility of Frameshift	No	Yes, if not in multiples of 3	Yes, if not in multiples of 3	Always
Functional Consequences	Protein may be normal, altered, or truncated	Protein may be nonfunctional or gain a novel function	May lead to loss of essential protein function	Usually results in nonfunctional or harmful proteins
Severity of Effect	Mild to severe, depending on position and type	Often severe if it causes a frameshift	Often severe if it causes a frameshift	Usually severe due to a major change in protein structure
Example	Sickle Cell Anaemia (missense mutation in β-globin gene)	Tay-Sachs disease (insertion in the HEXA gene)	Cystic Fibrosis (3-base pair deletion in the CFTR gene)	Huntington’s disease (triplet repeat expansion leads to a frameshift in the coding region)

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Causes of Mutations And Their Types

Mutations can be due to a variety of sources and can be broadly categorised into spontaneous and induced mutations. A basic comparison between both of them is discussed below:

Feature	Spontaneous Mutations	Induced Mutations
Definition	Mutations that occur naturally without any external influence	Mutations that occur due to exposure to external physical, chemical, or biological agents (mutagens)
Major Cause	Internal cellular processes (e.g., DNA replication errors, spontaneous base changes)	Environmental mutagens such as chemicals, radiation, or biological agents
Sub-types	1. Errors during DNA replication 2. Tautomeric shifts	1. Chemical mutagens 2. Physical mutagens 3. Biological agents
Mechanism	DNA polymerase misincorporates bases Base tautomerism leads to incorrect base pairing	Mutagens alter base structure or cause strand damage Foreign DNA integration alters gene function
Example of Mechanism	Tautomeric shift: Adenine pairs with cytosine instead of thymine DNA replication errors cause point mutations	Base analogues: mimic real bases and get incorporated UV radiation causes thymine dimers Viruses: cause gene disruption
Type of Mutation Caused	Often point mutations (e.g., transition or transversion)	Can cause point mutations, insertions, deletions, frameshifts, or chromosomal aberrations
Repair Possibility	May be repaired by proofreading or mismatch repair systems	It may overwhelm repair systems depending on the dose or intensity of the mutagen
Examples	Spontaneous base deamination Tautomeric base pairing	UV radiation (thymine dimers) Alkylating agents Retrovirus integration
Significance	Source of natural genetic variation	Used in experimental mutagenesis and linked to mutagen-induced diseases (e.g., cancer)

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Frequently Asked Questions (FAQs)

1. What is a mutation, and how does it happen?

It is the change in the DNA sequence, which can occur either of its own accord or through induction via assorted chemicals, radiation, or biological agents. The spontaneous mutation happens due to intrinsic replication errors and tautomeric shifts, and the induced one because of mutagen actions.

2. How is DNA repaired?

DNA repair mechanisms detect and subsequently correct errors in the DNA sequence to ensure the integrity of genetic material. Mechanisms among others include mismatch repair, rectifying replication errors; base excision repair, responsible for removing damaged bases; and nucleotide excision repair, which excises bulky DNA lesions.

3. What are the types of mutation?

There are point mutations such as substitutions, insertions, and deletions, and chromosomal mutations like deletions, duplications, inversions, and translocations. While point mutations affect a single nucleotide, chromosomal mutations will involve bigger segments of DNA.

4. What are the effects of Mutations on Protein Function?

One consequence of mutations is a change in the composition of amino acids in proteins. Misconformation in such proteins can result in changes in their structure and function. The changed protein may become nonfunctional, partially functional, or even attain a new function. Some mutations, however, referred to as silent mutations, do not change the functioning of proteins at all.

5. What is the role of mutations in evolution?

Mutations are a source of variation—a requirement necessary for evolution. Beneficial mutations enhance survival and reproduction, while harmful mutations, through selection pressure on them, ultimately are removed from the gene fund over time.

6. How do spontaneous mutations differ from induced mutations?

Spontaneous mutations occur naturally without any external influence, often due to errors in DNA replication or spontaneous chemical changes in DNA. Induced mutations, however, are caused by exposure to external mutagens such as radiation, chemicals, or certain viruses. The rate of induced mutations can be much higher than spontaneous mutations.

7. What is the significance of mutations in non-coding regions of DNA?

Mutations in non-coding regions can still have significant effects, even though they don't directly alter protein sequences. These mutations can affect gene regulation, splicing patterns, or the production of non-coding RNAs. For example, mutations in promoter regions can alter gene expression levels, while mutations in introns can affect splicing and lead to abnormal proteins.

8. How do DNA repair mechanisms work to prevent mutations?

DNA repair mechanisms are cellular processes that identify and correct damage to DNA molecules. There are several types of repair mechanisms, including:

9. How can epigenetic changes be mistaken for mutations?

Epigenetic changes, such as DNA methylation or histone modifications, can alter gene expression without changing the DNA sequence. These changes can be inherited and may appear to have effects similar to mutations. However, unlike mutations, epigenetic changes are potentially reversible and do not involve alterations to the genetic code itself. This distinction is important for understanding the molecular basis of inheritance and variation.

10. What is the relationship between mutations and evolution?

Mutations are the primary source of genetic variation, which is essential for evolution. They provide the raw material upon which natural selection acts. Beneficial mutations can increase an organism's fitness and be passed on to future generations, leading to evolutionary changes over time. Neutral mutations can also play a role in genetic drift and contribute to evolutionary processes.

11. How do point mutations differ from frameshift mutations?

Point mutations involve changes in a single nucleotide, while frameshift mutations involve the insertion or deletion of nucleotides that are not multiples of three. Point mutations may or may not alter the amino acid sequence, whereas frameshift mutations typically change the entire reading frame, resulting in a completely different protein sequence downstream of the mutation site.

12. What are the three main types of point mutations?

The three main types of point mutations are:

13. How can a silent mutation occur?

A silent mutation occurs when a change in the DNA sequence does not alter the amino acid encoded by the codon. This is possible due to the redundancy of the genetic code, where multiple codons can code for the same amino acid. For example, both UCU and UCC code for serine, so a mutation from UCU to UCC would be silent.

14. What is the difference between a missense and a nonsense mutation?

A missense mutation results in a codon that codes for a different amino acid, potentially altering the protein's structure and function. A nonsense mutation, on the other hand, changes a codon to a stop codon, resulting in a truncated protein. Nonsense mutations often have more severe consequences as they can lead to non-functional proteins.

15. What is the difference between germline and somatic mutations?

Germline mutations occur in reproductive cells (eggs or sperm) and can be passed on to offspring, potentially affecting all cells in the resulting organism. Somatic mutations occur in non-reproductive body cells and are not inherited by offspring. They can, however, lead to conditions like cancer if they affect genes controlling cell division.

16. What is the role of DNA polymerase proofreading in mutation prevention?

DNA polymerase proofreading is a built-in error-checking mechanism during DNA replication. As DNA polymerase adds nucleotides to the growing DNA strand, it can detect and correct mismatched base pairs. This proofreading ability significantly reduces the error rate during replication, helping to prevent mutations from occurring. However, it's not perfect, and some errors can still slip through.

17. How do insertions and deletions (indels) affect protein function?

Insertions and deletions can have significant effects on protein function, especially if they are not multiples of three nucleotides. They can cause frameshift mutations, altering the entire amino acid sequence downstream of the mutation site. This often results in a non-functional protein. Even in-frame indels (multiples of three nucleotides) can alter protein structure and function by adding or removing amino acids from the sequence.

18. How do mutations in regulatory regions affect gene expression?

Mutations in regulatory regions, such as promoters, enhancers, or silencers, can significantly impact gene expression without changing the protein-coding sequence. These mutations can:

19. What is the difference between a transition and a transversion mutation?

Transition mutations involve the substitution of one purine for another purine (A↔G) or one pyrimidine for another pyrimidine (C↔T). Transversion mutations involve the substitution of a purine for a pyrimidine or vice versa (e.g., A↔C, A↔T, G↔C, G↔T). Transitions are generally more common than transversions due to the chemical similarity of the bases involved.

20. How do mutations contribute to antibiotic resistance in bacteria?

Mutations can contribute to antibiotic resistance in bacteria through several mechanisms:

21. What is a mutation at the molecular level?

A mutation is a permanent change in the DNA sequence of an organism's genome. At the molecular level, this can involve alterations in single nucleotides, insertions or deletions of DNA segments, or changes in chromosome structure. These changes can affect gene function and potentially impact the organism's phenotype.

22. How do mutations in mitochondrial DNA differ from nuclear DNA mutations?

Mitochondrial DNA (mtDNA) mutations differ from nuclear DNA mutations in several ways:

23. What is the significance of synonymous mutations?

Synonymous mutations change the DNA sequence without altering the amino acid sequence of the protein. While once thought to be "silent," these mutations can have significant effects:

24. What is the relationship between DNA methylation and mutation rates?

DNA methylation, an epigenetic modification, can influence mutation rates in several ways:

25. What is the concept of mutator phenotype in cancer?

The mutator phenotype refers to an increased mutation rate in cancer cells due to defects in DNA repair or replication fidelity. This phenotype:

26. How do transposons contribute to mutations?

Transposons, or "jumping genes," are DNA sequences that can move from one location in the genome to another. This movement can cause mutations by inserting into or near genes, disrupting their function. Transposons can also cause deletions, duplications, or inversions of DNA segments when they move, contributing to genomic instability and potentially leading to evolutionary changes.

27. How do chemical mutagens cause DNA damage?

Chemical mutagens can cause DNA damage through various mechanisms:

28. What is the significance of hotspots in mutation?

Mutation hotspots are specific locations in the genome where mutations occur more frequently than expected by chance. These hotspots can be due to various factors, such as DNA sequence composition, chromatin structure, or exposure to specific mutagens. Understanding hotspots is important for predicting mutation rates, studying evolutionary processes, and identifying potential causes of genetic diseases.

29. What is the relationship between DNA repair and cancer?

DNA repair mechanisms are crucial for preventing cancer. Defects in DNA repair genes can lead to an accumulation of mutations, increasing the risk of cancer development. For example, mutations in the BRCA1 and BRCA2 genes, which are involved in double-strand break repair, are associated with increased risk of breast and ovarian cancers. Understanding this relationship is important for cancer research and developing targeted therapies.

30. How do environmental factors influence mutation rates?

Environmental factors can influence mutation rates in several ways:

31. What is the concept of mutational load?

Mutational load refers to the cumulative effect of deleterious mutations in a population. It's the reduction in average fitness of individuals due to the presence of harmful mutations. This concept is important in population genetics and evolutionary biology, as it helps explain phenomena like inbreeding depression and the maintenance of sexual reproduction. Understanding mutational load is crucial for predicting the long-term genetic health of populations.

32. What is the concept of mutation-selection balance?

Mutation-selection balance refers to the equilibrium between the introduction of deleterious mutations and their removal by natural selection. This balance helps explain why harmful alleles persist in populations at low frequencies. It's an important concept in population genetics, helping to understand the maintenance of genetic variation and the genetic load in populations.

33. How do chromosomal aberrations differ from gene mutations?

Chromosomal aberrations involve large-scale changes in chromosome structure or number, while gene mutations are smaller-scale changes within individual genes. Chromosomal aberrations include:

34. What is the role of mutation in the development of cancer?

Mutations play a crucial role in cancer development through a multi-step process:

35. How do mutations contribute to genetic diversity within a population?

Mutations contribute to genetic diversity by:

36. How do mutations in splice sites affect gene expression?

Mutations in splice sites can significantly impact gene expression by:

37. How do mutations in non-coding RNAs affect cellular processes?

Mutations in non-coding RNAs can have significant impacts on cellular processes:

38. What is the role of mutation in the development of genetic disorders?

Mutations play a central role in genetic disorders by:

39. How do mutations contribute to the evolution of viral genomes?

Mutations are key drivers of viral evolution:

40. What is the significance of neutral mutations in evolution?

Neutral mutations, which don't affect an organism's fitness, are important in evolution:

41. How do mutations in DNA repair genes affect genome stability?

Mutations in DNA repair genes can significantly impact genome stability:

42. What is the concept of adaptive mutation?

Adaptive mutation refers to the idea that organisms can increase their mutation rate in response to stress or challenging environments. This concept suggests:

43. How do mutations in telomere maintenance genes affect cellular aging?

Mutations in telomere maintenance genes can significantly impact cellular aging: