AP Syllabus focus:
‘Point, frameshift, nonsense, and silent mutations represent different changes to nucleotide sequences that can differently impact resulting polypeptides.’
Gene-level mutations change the nucleotide sequence within a single gene. Because genes are read as codons during translation, small sequence changes can have no effect, subtly alter one amino acid, or truncate or disrupt an entire polypeptide.
What “gene-level mutation” means for proteins
A protein-coding gene’s DNA sequence is transcribed into mRNA and read in triplet codons. The main way mutations change a polypeptide is by:
Changing one codon (potentially changing one amino acid)
Creating a premature stop codon
Shifting the reading frame so many downstream codons change
Point (substitution) mutations
A point mutation is a change in a single nucleotide pair, typically a base substitution.
Point mutation: a change affecting one nucleotide (or one nucleotide pair in DNA), often due to a substitution.
Point mutations can produce different outcomes depending on how the altered codon is interpreted by the genetic code.
This codon table maps each mRNA triplet codon to its amino acid (or a stop signal), making it easy to see why some base substitutions are silent due to redundancy in the genetic code. It also highlights how a single substitution can turn a sense codon into a stop codon (nonsense mutation). Use it as a reference when predicting polypeptide-level effects from specific nucleotide changes. Source
Silent mutations (a type of point mutation)
A silent mutation is a point mutation that does not change the amino acid encoded.
Common cause: redundancy (degeneracy) of the genetic code (multiple codons specify the same amino acid)
Typical outcome: no change to the primary structure of the polypeptide
Important nuance: although “silent” at the amino acid level, AP Biology emphasis is that the resulting polypeptide sequence is unchanged
Nonsense mutations (a type of point mutation)
A nonsense mutation is a point mutation that converts an amino-acid codon into a stop codon.
Outcome: premature termination of translation
Polypeptide effect: shortened protein, often nonfunctional because key domains may be missing
The earlier the stop appears in the coding sequence, the more severe the likely loss of function
Frameshift mutations (insertions/deletions)
Frameshift mutations result from nucleotide insertions or deletions that change how codons are grouped, shifting the reading frame from the mutation onward.
This diagram contrasts a normal open reading frame with a frameshift caused by a nucleotide insertion. It shows how regrouping mRNA into new triplet codons changes many downstream amino acids and can introduce a premature stop codon. The side-by-side layout makes the “from the mutation onward” effect of frameshifts visually explicit. Source
Frameshift mutation: an insertion or deletion of nucleotides that shifts the triplet reading frame, altering all downstream codons.
Because codons are read in groups of three, frameshifts most often occur when the number of nucleotides added or removed is not a multiple of 3.
Effect on codons: many downstream codons become different
Effect on polypeptide: multiple amino acid changes and frequently an early stop codon appears
Typical outcome: large change in protein sequence and function compared with most single-base substitutions
How these mutation types differently impact polypeptides
The specification focus is that point, frameshift, nonsense, and silent mutations represent different nucleotide changes with different impacts on polypeptides:
Silent (point substitution): same amino acid sequence → usually same polypeptide length and composition
Point substitution (general): may change one codon → can change one amino acid (potentially altering folding/function)
Nonsense (point substitution to stop): truncated polypeptide → often loss of function
Frameshift (indel): many codons altered downstream → often dramatically altered or truncated polypeptide
Mutation impact depends strongly on where it occurs (e.g., early vs late in the coding region) and whether the changed amino acid is critical for structure or activity.
FAQ
A frameshift changes how every downstream base is grouped into codons.
This typically alters many amino acids, not just one.
It also increases the chance of generating an early stop codon, shortening the protein.
Yes, if the amino acid change is conservative and does not disrupt folding or an active/binding site.
Protein impact depends on the role of that residue in structure and function, not just whether a substitution occurred.
Codons are read in triplets.
Indels of $3, 6, 9, \dots$ nucleotides add/remove whole amino acids without shifting the frame.
Indels of $1$ or $2$ nucleotides shift the frame and change downstream codons.
Not always. If the stop codon occurs near the end of the coding sequence, the protein may retain some domains.
However, truncation commonly disrupts essential regions, so loss of function is frequent.
A substitution’s effect depends on codon context.
If the altered codon still specifies the same amino acid, it is silent.
If it changes to a different amino acid or a stop codon, it is not silent.
Practice Questions
State the type of gene-level mutation described in each case: a) A DNA base substitution changes to , and the encoded amino acid remains glutamate.
b) A base substitution changes a codon for an amino acid into a stop codon.
c) A single nucleotide is deleted from the coding sequence, altering all downstream codons. (3 marks)
a) Silent mutation (1)
b) Nonsense mutation (1)
c) Frameshift mutation (1)
Explain how different gene-level mutations can produce different polypeptide outcomes. In your answer, refer to silent, nonsense, point, and frameshift mutations and their effects on codons and translation. (6 marks)
Describes a point mutation as a base substitution affecting one nucleotide/codon (1)
Explains silent mutation: substitution changes codon but not amino acid due to degeneracy (1)
Explains nonsense mutation: substitution creates stop codon causing premature termination/truncated polypeptide (1)
Describes frameshift as insertion/deletion shifting reading frame (1)
Explains frameshift alters many downstream codons/amino acids (1)
States frameshift often introduces a premature stop and/or causes major loss of function compared with silent (1)
