A single mutation in a nucleotide base pair resulting in a termination codon is known as _________?

Correct Answer: C. Nonsense mutation

A nonsense mutation is a point mutation in which a single nucleotide substitution results in a codon that codes for a stop signal (UAA, UAG, or UGA) instead of an amino acid. This premature termination codon (PTC) causes translation to halt prematurely, producing a truncated, non-functional protein. The discriminating feature is the creation of a stop codon from a sense codon—not merely any change in the DNA sequence. Clinically, nonsense mutations are among the most severe mutations because they result in loss of protein function. Classic examples include certain mutations in the CFTR gene (cystic fibrosis) and DMD gene (Duchenne muscular dystrophy) seen in Indian populations. The severity depends on where the PTC occurs: early PTCs cause more severe phenotypes due to greater loss of protein domains. This contrasts with missense mutations (which change the amino acid but preserve the reading frame) and silent mutations (which do not change the amino acid due to codon degeneracy). The term "nonsense" reflects that the mutated codon produces no sense—it terminates translation instead of coding for an amino acid.

Why the other options are wrong

A. Stop mutation — This is wrong because 'stop mutation' is not a recognized genetic term in standard nomenclature. While it descriptively sounds like it could refer to premature termination, the correct scientific term is nonsense mutation. NBE uses this distractor to test whether students know the precise terminology used in molecular biology and genetics textbooks. B. Silent mutation — This is wrong because a silent mutation is a nucleotide change that does not alter the amino acid sequence due to codon degeneracy (wobble base pairing). It produces no phenotypic effect. A nonsense mutation, by contrast, creates a stop codon and dramatically truncates the protein. NBE pairs these to trap students who confuse any 'single nucleotide change' with silent mutations. D. Missense mutation — This is wrong because a missense mutation changes one codon to another that codes for a different amino acid, but translation continues normally. The protein is full-length but altered. A nonsense mutation, conversely, creates a stop codon and halts translation prematurely. NBE uses this to test discrimination between point mutations that change amino acids versus those that terminate translation.

High-Yield Facts

Mnemonics

NSMM: Nonsense = Stop codon Nonsense = Stop codon (creates termination signal). Missense = Modified amino acid (different AA, translation continues). Mutations: Nonsense is the 'no-sense' one—it stops making sense. Point Mutation Hierarchy Silent (no change) → Missense (AA change, continues) → Nonsense (stop codon, truncates). Remember: Silent is safest, Nonsense is severest.

NBE Trap

NBE pairs "stop mutation" (a plausible-sounding but non-standard term) with "nonsense mutation" to test whether students have memorized the correct genetic nomenclature. Students who reason "it creates a stop codon, so it's a stop mutation" will fall into this trap—the correct term is nonsense, not stop.

Clinical Pearl

In Indian clinical practice, nonsense mutations in genes like DMD (Duchenne muscular dystrophy) and CFTR (cystic fibrosis, though rare) cause severe, early-onset disease because the truncated protein is non-functional. Recognizing nonsense mutations is critical for genetic counseling and understanding why some families show severe phenotypes despite only a single nucleotide change.

_Reference: Robbins & Cotran Pathologic Basis of Disease, Ch. 5 (Genetic Disorders); Guyton & Hall Textbook of Medical Physiology, Ch. 3 (Genetic Control of Protein Synthesis); KD Tripathi Essentials of Medical Pharmacology, Ch. 1 (Genetics)_