Out of the four options listed, a deletion is a frameshift mutation. Substitution, nonsense, and silent mutations all involve swapping one nucleotide for another without changing the total number of bases in the sequence. A deletion removes one or more nucleotides, which shifts how the entire gene is read from that point forward.
Why Deletion Causes a Frameshift
Your cells read DNA in groups of three bases, called codons. Each codon maps to a specific amino acid, and amino acids are the building blocks of proteins. When a deletion removes one or two nucleotides (or any number that isn’t a multiple of three), every codon after the deletion gets regrouped. Think of it like removing a letter from a sentence where spaces fall every three characters. The letters themselves haven’t changed, but the words are now completely different.
This regrouping scrambles the instructions for every amino acid downstream. The result is usually a nonfunctional protein, either because the wrong amino acids are strung together or because the shifted reading frame accidentally creates a stop signal that cuts the protein short. In Tay-Sachs disease, for example, a single deleted cytosine at one position in the gene causes the protein to terminate just four codons later, lopping off 22 amino acids that the protein needs to function.
Why the Other Three Are Not Frameshift Mutations
Substitution, nonsense, and silent mutations are all types of point mutations. They replace one nucleotide with a different one, keeping the total count the same. Because no bases are added or removed, the three-letter reading frame stays intact.
- Substitution (missense): One nucleotide is swapped, changing a single codon so it codes for a different amino acid. The rest of the protein is unaffected.
- Nonsense: A specific type of substitution where the swapped nucleotide turns a normal codon into a premature stop signal. The protein gets cut short, but the reading frame itself hasn’t shifted.
- Silent: A substitution that changes a nucleotide but, because of redundancy in the genetic code, the codon still codes for the same amino acid. The protein comes out identical.
The key distinction is that none of these add or remove bases. They swap one for another, so the grouping of every downstream codon remains unchanged.
Not Every Deletion Is a Frameshift
There’s one important caveat. If a deletion removes exactly three nucleotides (or any multiple of three), the reading frame stays intact. You lose one or more amino acids from the protein, but every codon after the deletion is still read correctly. This is called an in-frame deletion, and it tends to be less damaging than a true frameshift because the rest of the protein can still fold and function normally, depending on how critical those missing amino acids are.
A frameshift specifically requires that the number of inserted or deleted bases is not a multiple of three. Removing one, two, four, or five bases all cause frameshifts. Removing three or six does not.
How Frameshifts Differ From Nonsense Mutations
Frameshifts and nonsense mutations can look similar in their end result because both often produce a shortened, nonfunctional protein. The difference is in the mechanism. A nonsense mutation is a single-base swap that directly creates a stop codon at one specific location. A frameshift scrambles the entire downstream sequence, which frequently generates a stop codon somewhere along the way by accident. In a frameshift, the stop codon is a consequence of the garbled code, not the mutation itself.
This also means frameshifts tend to be more destructive. A nonsense mutation preserves the correct amino acid sequence up to the point of the premature stop. A frameshift produces wrong amino acids from the deletion point onward, so even the portion of the protein that does get built is likely misfolded and nonfunctional.