15. A hypothetical gene encodes a protein with the following amino acid sequence:
Phe- Pro- Thr- Ala- Val-Arg- Ser
A mutation of single nucleotide alters the amino acid sequence to
Phe- Leu- Leu- Leu- Leu-
A second single nucleotide mutation occurs in same gene restoring back the amino acid sequence to the original. The following statements were made regarding the nature and location of the first mutation and that of the intragenic suppressor mutation:
A. The first mutation is a deletion in the second codon.
B. The first mutation is an insertion in the second codon.
C. The intragenic suppressor mutation is an insertion in the second codon
D. The intragenic suppressor mutation is a deletion in the third codon
Which combination of the above statements is correct?
(1) A and C (2) A and D
(3) B and C (4) B and D
Introduction
Frameshift mutation intragenic suppressor questions test understanding of how single nucleotide indels shift reading frames in genetics, leading to polypeptide changes like from Phe-Pro-Thr-Ala-Val-Arg-Ser to Phe-Leu-Leu-Leu-Leu-, then back via second mutation. This CSIR NET Life Sciences query highlights deletion/insertion effects and suppressor restoration. Correct combination reveals precise locations for original sequence recovery.
Original Sequence Codons
Assume standard mRNA codons: Phe (UUU), Pro (CCU), Thr (ACU), Ala (GCU), Val (GUU), Arg (CGA), Ser (UCU). Nucleotide sequence: UUU-CCU-ACU-GCU-GUU-CGA-UCU (21 nt). Translation reads triplets from start.
First Mutation Analysis
Option A (Deletion in second codon): Deleting one nucleotide from Pro codon (e.g., position 4, C from CCU) yields UUU-CUA-CUG-CUG-UUG-AGC-UCU. Codons become Phe-Leu-Leu-Leu-Leu-Ser-Leu, matching mutant Phe-Leu-Leu-Leu-Leu- (early termination implied). Frameshift +1 from deletion alters downstream frame to leucine-rich (CUX/UUA).
Option B (Insertion in second codon): Inserting one nucleotide (e.g., C after UUU, making UUU-C-CCU…) shifts -1 frame early, unlikely producing exact Phe-Leu run without precise Leu codons aligning post-Phe. Simulations show mismatch to continuous Leus.
Suppressor Mutation Effects
Option C (Insertion in second codon): Adding back in same codon as first mutation rarely restores fully; frameshifts need compensatory shift nearby, not same site for exact original.
Option D (Deletion in third codon): After first deletion (A true), frame +1 persists. Deleting one nt from original Thr codon (now shifted) in mutant (e.g., position ~9-10) restores frame: post-double mutation, triplets realign to Pro-Thr-Ala-Val-Arg-Ser. Compensatory -1 shift cancels +1, yielding wild-type.
Correct Combination
Option A and D fit: first deletion (second codon) causes frameshift to Leus; suppressor deletion (third codon) restores reading frame precisely. Thus, (2) A and D. Other pairs fail: B-C same-site illogical; B-D insertion not Leu-triggering; A-C no compensation.
This frameshift mutation intragenic suppressor exemplifies CSIR NET genetics trap on indel polarity and position.
