8. A frameshift mutation is caused by ____.
(A) 5-Bromouracil
(B) Acridine
(C) Glutathione
(D) Hypoxanthine
Frameshift Mutation Explained: How Acridine Causes Frameshift Mutations
Introduction
Mutations are permanent alterations in the DNA sequence that can change gene function and protein synthesis. They are one of the primary sources of genetic variation and play a significant role in evolution, inherited diseases, cancer development, and microbial adaptation. Mutations may occur naturally during DNA replication or may be induced by physical, chemical, or biological mutagens. Depending on their nature, mutations can be classified as point mutations, frameshift mutations, chromosomal mutations, and genome mutations.
A frameshift mutation is one of the most severe forms of gene mutation because it alters the reading frame of messenger RNA during translation. This type of mutation usually results from the insertion or deletion of one or more nucleotides that are not in multiples of three. As a consequence, every codon downstream of the mutation changes, often producing a completely different amino acid sequence and frequently introducing a premature stop codon. Among chemical mutagens, acridine dyes are the classic agents responsible for inducing frameshift mutations because they insert themselves between adjacent DNA base pairs during replication.
Correct Answer
Correct Option: (B) Acridine
Detailed Explanation
Frameshift mutations occur when nucleotides are inserted into or deleted from a DNA sequence in numbers that are not divisible by three. Since the genetic code is read in triplets (codons), such insertions or deletions shift the reading frame, altering every codon downstream of the mutation. This usually produces nonfunctional or severely altered proteins.
Acridine compounds, such as acridine orange and proflavin, are intercalating agents. Their flat aromatic structure allows them to insert between adjacent DNA base pairs during replication. This intercalation distorts the DNA helix and causes DNA polymerase to insert or delete nucleotides, leading to frameshift mutations.
Because acridine specifically induces insertion and deletion mutations that change the reading frame, it is regarded as the classical chemical mutagen responsible for frameshift mutations.
Mechanism of Frameshift Mutation by Acridine
Acridine molecules slide between stacked DNA base pairs during replication. This changes the spacing between nucleotides and interferes with the normal movement of DNA polymerase. As a result, the enzyme may accidentally insert an extra nucleotide or skip one nucleotide during DNA synthesis. These insertion or deletion events alter the triplet reading frame, producing a frameshift mutation.
Explanation of Each Option
Option (A): 5-Bromouracil
This option is incorrect. 5-Bromouracil is a base analogue of thymine. It becomes incorporated into DNA and undergoes abnormal base pairing, causing transition point mutations rather than frameshift mutations.
Option (B): Acridine
This option is correct. Acridine dyes are intercalating agents that insert between DNA base pairs and induce nucleotide insertions or deletions, producing frameshift mutations.
Option (C): Glutathione
This option is incorrect. Glutathione is an antioxidant that protects cells against oxidative damage. It is not a mutagen and does not induce frameshift mutations.
Option (D): Hypoxanthine
This option is incorrect. Hypoxanthine is formed by the deamination of adenine and causes abnormal base pairing, leading primarily to transition mutations, not frameshift mutations.
Why Option (B) is Correct
Acridine molecules intercalate between DNA base pairs, disrupting normal DNA replication and causing insertion or deletion of nucleotides. Since these mutations alter the reading frame of the genetic code, they are classified as frameshift mutations.
Comparison of All Options
| Option | Compound | Primary Effect | Status |
|---|---|---|---|
| A | 5-Bromouracil | Transition point mutation | Incorrect |
| B | Acridine | Frameshift mutation (Insertion/Deletion) | Correct |
| C | Glutathione | Antioxidant | Incorrect |
| D | Hypoxanthine | Transition point mutation | Incorrect |
Common Chemical Mutagens and Their Effects
| Mutagen | Mechanism | Mutation Produced |
|---|---|---|
| Acridine | DNA intercalation | Frameshift mutation |
| 5-Bromouracil | Base analogue | Transition mutation |
| Nitrous Acid | Deamination | Transition mutation |
| Hydroxylamine | Cytosine modification | Transition mutation |
| Ethyl Methanesulfonate (EMS) | Alkylation | Point mutation |
Frameshift Mutation vs Point Mutation
| Feature | Frameshift Mutation | Point Mutation |
|---|---|---|
| Cause | Insertion or deletion | Single base substitution |
| Reading Frame | Shifted | Unaffected |
| Protein Sequence | Usually extensively altered | Usually affects one amino acid |
| Severity | Generally high | Variable |
Biological Significance
Frameshift mutations often have severe biological consequences because they change every codon downstream of the mutation. This frequently results in truncated or nonfunctional proteins due to the appearance of premature stop codons. Such mutations are associated with numerous inherited disorders, cancers, and microbial mutations affecting antibiotic resistance. Understanding mutagenic mechanisms is therefore essential in genetics, molecular biology, medicine, and biotechnology.
Final Answer
Acridine is an intercalating agent that inserts between DNA base pairs and causes nucleotide insertions or deletions during DNA replication, resulting in frameshift mutations.
Correct Option: (B) Acridine
