An insertion adds nucleotides to a DNA sequence and a deletion removes them. In a protein-coding sequence, the consequence depends strongly on whether the number of added or removed nucleotides is a multiple of three.

Frameshift changes

Because mRNA codons are read in groups of three, an insertion or deletion whose length is not a multiple of three changes how downstream nucleotides are grouped. This is a frameshift.

Suppose an mRNA is read as

AUG | GCU | UAC | GGA | ...
Met | Ala | Tyr | Gly | ...

Deleting the first G of the second codon produces a regrouped sequence:

AUG | CUU | ACG | GA...
Met | Leu | Thr | ...

The downstream amino-acid sequence changes, and a premature stop codon may appear.

In-frame changes

If the number of inserted or deleted nucleotides is a multiple of three, the downstream reading frame can remain unchanged. Deleting one complete codon, for example, removes one amino acid while preserving the grouping of later codons.

An in-frame change can still have a large effect if the affected amino acids are important for protein structure or function.

The distinction is therefore:

• insertion/deletion describes the underlying DNA sequence change;
• frameshift describes a coding consequence when the change length is not divisible by three;
• functional severity depends on where the change occurs and what the affected sequence does.