Which of the following is a consequence of a frameshift mutation?

Core Concept

PILLAR 1 — MOLECULAR/CONCEPTUAL MECHANISM

Step-by-Step Analysis

The genetic code is read by the ribosome in non-overlapping triplets called codons, each specifying one of twenty amino acids or a translation-termination signal. This triplet-based decoding establishes a fixed reading frame that begins at the AUG start codon on the messenger RNA. A frameshift mutation alters this reading frame by inserting or deleting a number of nucleotides not divisible by three. When the ribosome encounters the shifted sequence, every downstream codon is re-parsed into an entirely different set of triplets. The resulting polypeptide bears no resemblance to the wild-type protein beyond the point of mutation, because the ribosome now recruits completely different transfer RNAs—each charged with its specific amino acid by the corresponding aminoacyl-tRNA synthetase—based on the new codon identities. Additionally, the shifted frame frequently generates a premature stop codon (UAA, UAG, or UGA), causing early translation termination. The misfolded, truncated polypeptide is often targeted for proteasomal degradation via ubiquitin tagging, effectively eliminating functional protein from the cell. This molecular cascade—altered codons, incorrect amino acid incorporation, premature termination, and protein destruction—stems directly from the disrupted reading frame.

Why Other Options Are Wrong

PILLAR 2 — STEP-BY-STEP LOGIC

The question specifically asks for a consequence of a frameshift mutation, meaning the phenotypic or molecular outcome rather than the mutational event itself. Option C, "Alteration of the reading frame of a gene," precisely identifies this downstream outcome: the triplet parsing boundary shifts, scrambling every codon downstream of the mutation site. This consequence manifests regardless of whether the causative event is an insertion of one nucleotide, a deletion of four nucleotides, or any other indel whose length is not a multiple of three. The logical chain connects the molecular mechanism (triplet codon reading) to the observable result (shifted reading frame), making C the only option that describes what a frameshift mutation causes at the translational level. The reading frame alteration distinguishes frameshifts from other mutation classes: point substitutions, for example, change only a single codon without shifting the triplet boundary.

PILLAR 3 — DISTRACTOR ANALYSIS

Option A ("Insertion or deletion of a single nucleotide") describes a potential cause of a frameshift, not a consequence. The question demands the outcome of the mutation, not its mechanistic origin. Furthermore, this option is overly restrictive: frameshifts can arise from insertions or deletions of any number of nucleotides not divisible by three (e.g., two, four, five). Students selecting A conflate mutagenic events with their phenotypic consequences.

Option B ("Substitution of a single nucleotide") describes a point mutation mechanism entirely distinct from frameshift mutations. A substitution replaces one base with another—such as adenine swapped for guanine—but does not alter the number of nucleotides in the sequence. Consequently, the reading frame remains intact, and only the affected codon changes. Students choosing B fail to distinguish between substitution mutations (missense, nonsense, silent) and indel mutations that shift the reading frame.

Option D ("Silencing of gene expression") mischaracterizes the consequence of a frameshift. While a frameshift often produces a nonfunctional protein, the gene itself continues to be transcribed and translated—the mRNA is still produced, and the ribosome still initiates at the same AUG codon. Silencing implies transcriptional shutdown, typically achieved through promoter methylation, histone deacetylation, or repressor protein binding to regulatory sequences. Students selecting D confuse loss of functional protein with cessation of gene expression, failing to recognize that a frameshift mutation operates at the level of mRNA translation fidelity rather than transcriptional regulation.