A mutation occurs in a gene such that a single nucleotide pair is deleted from the coding region of the DNA. Which of the following best predicts the effect of this mutation on the resulting polypeptide?

Core Concept

PILLAR 1 — MOLECULAR/CONCEPTUAL MECHANISM

Step-by-Step Analysis

The genetic code operates as a non-overlapping, triplet-based system read by the ribosome during translation. Each codon—three consecutive ribonucleotides in the mature mRNA—specifies one amino acid via complementary base pairing with the anticodon loop of a charged tRNA molecule in the ribosomal A site. The reading frame is established when the small ribosomal subunit recognizes the start codon (AUG) with the help of initiation factors, and this frame is maintained with absolute precision as the ribosome translocates along the mRNA transcript in the 5'→3' direction.

Why Other Options Are Wrong

A deletion of a single nucleotide pair from the coding region of the DNA molecule propagates through the central dogma: during DNA replication, the mutated template strand directs synthesis of a complementary strand missing the corresponding nucleotide. When RNA polymerase II transcribes this mutated gene during transcription in the eukaryotic nucleus, the resulting pre-mRNA lacks one ribonucleotide. After RNA processing (5' capping, polyadenylation, and splicing of introns by the spliceosome), the mature mRNA still carries this deletion into the cytoplasm. Because the ribosome reads in triplets, removing one nucleotide shifts the reading frame at that precise position. Every codon downstream of the deletion is now composed of an altered combination of nucleotides—a different first position, second position, and third position relative to the original frame. This frameshift mutation produces a cascade of incorrect amino acid incorporations as different tRNA molecules recognize the shifted codons. Furthermore, the new reading frame is statistically very likely to encounter one of the three stop codons (UAA, UAG, or UGA) prematurely, resulting in a truncated polypeptide released from the ribosome by release factor binding.

PILLAR 2 — STEP-BY-STEP LOGIC

The question specifies a deletion of a single nucleotide pair from the coding region. The word "single" is the critical detail: because the number of deleted nucleotides (one) is not a multiple of three, the reading frame cannot be preserved. Had three or six nucleotides been deleted, the frame would remain intact, and one or two amino acids would simply be absent from the final polypeptide. With a single-nucleotide deletion, the ribosome cannot "know" a nucleotide is missing; it continues reading in consecutive triplets, but every triplet after the deletion site is now a different sequence. Consider a hypothetical mRNA segment: AUG-CCU-GAA-UUU codes for Met-Pro-Glu-Phe. Deleting the second nucleotide (U) yields: AUG-CUG-AAU-UU..., which now reads Met-Leu-Asn..., with every subsequent amino acid changed. The correct answer (B) must reflect this fundamental alteration of all downstream codons and their corresponding amino acids, distinguishing the global disruption of a frameshift from the localized effects of substitution mutations.

PILLAR 3 — DISTRACTOR ANALYSIS

Option A likely states that only one amino acid is altered. This distractor exploits confusion between substitution mutations (missense mutations) and frameshift mutations. A missense mutation involves a nucleotide substitution that changes one codon, potentially altering one amino acid—for example, changing GAA (glutamate) to GUA (valine) in the beta-globin gene causes sickle cell disease. However, a deletion of one nucleotide is not a substitution; it shifts the entire downstream reading frame, affecting far more than a single amino acid residue.

Option C likely suggests the polypeptide is shortened by one amino acid without other changes. This traps students who incorrectly reason that deleting one nucleotide simply removes one amino acid from the chain. This reflects a fundamental misunderstanding of the triplet reading frame. Only a deletion of exactly three nucleotides (one full codon) would remove one amino acid while preserving the reading frame for all downstream residues. A single-nucleotide deletion cannot cleanly subtract one amino acid because it disrupts the codon boundaries entirely.

Option D likely proposes that the polypeptide remains unchanged or is functionally equivalent. This distractor appeals to students who conflate deletions with silent mutations—substitutions that, due to the degeneracy of the genetic code, produce a codon for the same amino acid (e.g., both GAA and GAG encode glutamate). Silent mutations preserve the polypeptide sequence, but deletions cannot be silent because they alter the spatial grouping of every downstream nucleotide into new, incorrect codons. The ribosome has no proofreading mechanism to detect a missing nucleotide and restore the original frame.