HSC Exam Practice

Sample response. A point mutation is a change to the DNA sequence affecting one base pair or a very small number of bases (such as a substitution, insertion or deletion of a single base).

Marking notes. 1 mark for "change to the DNA / base sequence"; 1 mark for restriction to one base pair (or small number of bases) — distinguishing it from a whole-chromosome change.

Sample response. In a substitution, one base in the DNA is replaced by a different base, while the total number of bases stays the same. In an insertion, one or more bases are added into the sequence, so the sequence becomes longer. In a deletion, one or more bases are removed from the sequence, so it becomes shorter.

Marking notes. 1 mark per mutation type correctly distinguished from the others (replace vs add vs remove). Max 3.

Sample response. The genetic code reads mRNA in codons of three bases, each specifying one amino acid (or a stop signal). A substitution changes one base of one codon. The mutation is silent if the new codon still codes for the same amino acid (e.g. GAA → GAG, both Glu) — the protein sequence is unchanged. It is missense if the new codon codes for a different amino acid (e.g. GAA → GUA, Glu → Val) — one amino acid in the polypeptide is replaced. It is nonsense if the new codon becomes a stop codon (UAA, UAG or UGA) — the ribosome terminates translation early and the polypeptide is truncated.

Marking notes. 1 mark for explaining silent (same amino acid, often via codon degeneracy); 1 mark for missense (different amino acid); 1 mark for nonsense (stop codon / truncation); 1 mark for using "codon" precisely throughout (not just "DNA section").

Sample response. A substitution alters only the single codon it lies within, so at worst it changes one amino acid (or none, if silent). A single-base insertion or deletion is not a multiple of three, so it shifts the reading frame from the mutation point onward. Every codon downstream is regrouped, so most of the amino acids after the mutation site are changed, and a stop codon usually appears earlier than normal by chance, producing a truncated, non-functional protein.

Marking notes. 1 mark for "substitution affects only one codon / at most one amino acid"; 1 mark for explicitly identifying the reading-frame shift caused by a single-base indel; 1 mark for the consequence — many altered downstream codons and/or a premature stop.

Sample response (a). As the codon position of the single-base deletion moves further along the gene, the polypeptide length produced increases. In each mutant, translation terminates a small number of amino acids (roughly 7–18) after the deletion site: codon 25 → 32 aa, codon 100 → 114 aa, codon 300 → 318 aa, codon 480 → 489 aa. None reach the wild-type length of 500 aa.

Sample response (b). A single-base deletion is not a multiple of three, so it shifts the reading frame from the deletion site onward. Every codon downstream is regrouped. Across regrouped sequence, one of the three stop codons (UAA, UAG, UGA) tends to appear within ~20 codons by chance — a premature stop codon — so the ribosome terminates translation soon after the deletion. At codon 25, this premature stop occurs very early and produces a 32-aa fragment that is almost certainly non-functional. At codon 480 the deletion lies near the natural stop, so the resulting 489-aa polypeptide is only 11 amino acids shorter than wild-type and most of the protein, including its functional regions, is intact.

Marking notes. Part (a) — 1 mark for "positive / increasing" relationship; 1 mark for using at least two data points or stating that translation stops a few aa after the deletion in every case. Part (b) — 1 mark for invoking reading-frame shift; 1 mark for the premature stop codon mechanism; 1 mark for explicitly contrasting the codon-25 (mostly missing) vs codon-480 (mostly intact) cases.

Sample response. Deleting three bases removes exactly one whole codon, so the reading frame is preserved for every codon downstream. The ribosome translates the rest of the mRNA in the original frame and terminates at the natural stop codon. The polypeptide produced is therefore one amino acid shorter than wild-type — approximately 499 amino acids long. Although the rest of the protein sequence is intact, the missing amino acid may still locally disrupt folding or function (analogous to ΔF508 CFTR in cystic fibrosis).

Marking notes. 1 mark for "reading frame preserved because three bases = one codon"; 1 mark for predicting a polypeptide length of approximately 499 aa (or "one amino acid shorter than wild-type"); 1 mark for noting that no frameshift occurs / no premature stop is introduced (or equivalent — that the rest of the protein is translated normally).

Sample response. The claim that point mutations "only ever cause small biological effects" is rejected. While a point mutation is by definition a base-level change, its biological consequences range from essentially none (silent substitutions) to lethal (frameshifts and active-site missense mutations), depending on the type of mutation and its position within the gene. The sickle-cell case (HbS) is a substitution at codon 6 of the HBB gene: GAG (Glu) → GUG (Val). The mutation type is mild — a single substitution producing a single missense change — yet because the polar, charged glutamate is replaced by a non-polar, hydrophobic valine on the surface of β-globin, haemoglobin polymerises into long fibres under low oxygen. Red blood cells distort into rigid sickles, block capillaries, are removed prematurely by the spleen, and the homozygous phenotype includes anaemia, pain crises and organ damage. A single base change therefore produces a dramatic, multi-organ phenotype because of its specific position on the haemoglobin protein. A frameshift example shows the same point at the other end of the spectrum: in Duchenne muscular dystrophy, a single-base deletion early in the DMD gene shifts the reading frame and introduces a premature stop codon within ~20 codons, truncating dystrophin and abolishing function — severe progressive muscle degeneration follows from the loss of just one base. By contrast, the same kind of frameshift very near the natural stop codon would shorten the protein by only a handful of residues and might be tolerated. Likewise, the three-base deletion in cystic fibrosis (ΔF508) removes one codon without a frameshift but still disrupts CFTR folding catastrophically. So mutation type sets the maximum disruption (substitution ≤ one amino acid change; single-base indel = whole downstream frame shifted) and position determines whether that disruption hits a functionally critical region. The original claim is wrong both at the level of type (frameshifts can devastate a protein) and at the level of position (even a single missense at a critical site, as in sickle cell, produces a major clinical effect). A point mutation's biological effect depends on type, position and protein context, not on the size of the DNA change.

Marking notes. 1 mark — Defines point mutation as a base-level DNA change and signals that the claim will be rejected. 1 mark — Correctly classifies HbS (substitution; missense; GAG → GUG; Glu → Val at codon 6 of HBB). 1 mark — Connects the Glu → Val change (polar/charged → non-polar/hydrophobic) to haemoglobin polymerisation and red blood cell sickling. 1 mark — Links sickling to the homozygous clinical phenotype (anaemia, capillary blockage, pain crises, organ damage) to show the magnitude of effect from a single base change. 1 mark — Uses a frameshift example (e.g. Duchenne, generic single-base deletion) with explicit reading-frame shift and premature stop codon mechanism. 1 mark — Uses position as a separate axis (e.g. frameshift near the start severe vs near the end mild; missense at active site vs surface loop). 1 mark — Reaches an explicit evaluative judgement that rejects "only small effects" and integrates both mutation type and position. 1 mark — Uses precise lesson terminology throughout (codon, reading frame, frameshift, missense, nonsense, silent, premature stop) and connects to the DNA → codon → amino-acid → protein → phenotype chain.