Suppressing Nonsense Mutations to Restore Polypeptide Length
A nonsense mutation introduces a premature stop codon (e.g., UAA, UAG, UGA) in the mRNA sequence. This causes the ribosome to terminate protein synthesis prematurely, resulting in a non-functional, truncated polypeptide.
To restore the synthesis of a full-length polypeptide, a second mutation is needed that can overcome the effect of the premature stop codon. This is known as a nonsense suppressor mutation.
Mechanism of Nonsense Suppression
- Mutations within a Transfer RNA (tRNA) gene are a common cause of nonsense suppression.
- A mutation can alter the tRNA's anticodon loop. If this altered tRNA can recognize the premature stop codon on the mRNA (e.g., UAG) but carries a specific amino acid (instead of releasing factors), it will insert that amino acid.
- This allows the ribosome to continue translation past the premature stop codon until it encounters the normal stop codon at the end of the coding sequence.
- The result is a full-length polypeptide chain, although it may contain an extra amino acid at the position of the original nonsense mutation.
Why Other Options Are Incorrect
- Mutations in Ribosomal protein genes or Ribosomal RNA (rRNA) genes (Options 1 and 4) primarily affect the structure and function of the ribosome itself. While they can cause translation defects, they don't specifically suppress nonsense codons in the way a mutant tRNA does.
- Mutations in DNA repair genes (Option 3) are involved in correcting errors in the DNA sequence and have no direct role in suppressing translational termination signals.
Therefore, introducing a mutation in a Transfer RNA gene is the strategy to obtain a full-length polypeptide when a nonsense mutation has occurred.
Important Questions from Mutations and Mutagenesis
Determine the correctness or otherwise of the following Assertion [a] and the Reason [r].
Assertion [a]: Chromosome mutations can change the structure of chromosomes.
Reason [r]: All chromosome mutations arise due to nondisjunction of chromosomes during mitosis or meiosis.A DNA sequence, 5'-ATGGACGTGCTTCCCAAAGCATCGGGC-3', is mutated to obtain
P. 5'-ATGGACGTGCTTCaCAAAGCATCGGGC-3′
Q. 5′-ATGGACGTGCTTCCCgAAAGCATCGGGC-3′
R. 5'-ATGGACGTGCTTCC-AAAGCATCGGGC-3′
S. 5'-ATGGACGTGCTTCCCAAtGCATCGGGC-3′
T. 5'-ATGGACGaGCTTCCCAAAGCATCGGGC-3′
[Point mutations are shown in the lower case or ‘–' within the sequences]
Which of the above mutant sequences DO NOT have frame-shift?
- A mutation in a gene that codes for a polypeptide results in a variant polypeptide that lacks the last three amino acids. What type of mutation is this?
Determine the correctness or otherwise of the following Assertion (a) and the Reason (r).
Assertion : N-methyl-N'-nitro-N-nitrosoguanidine (NTG) is an effective chemical mutagen.
Reason: Mutations induced by NTG mainly are the GC $\rightarrow$ AT transitions.
- Lysine is being produced in a lab-scale reactor by a threonine auxotroph. After 2 weeks of operation it was observed that the concentration of lysine in the reactor was gradually decreasing. Microbiological assays of reactor samples showed absence of contamination and recorded data showed no change in the operating conditions. The most probable reason for decrease in lysine concentration may be attributed to
