What mutation occurs when one or more nucleotides are added or removed in a way that is not divisible by three?

A frame-shift mutation occurs when nucleotides are added or removed from the DNA sequence in numbers that are not divisible by three. This type of mutation is particularly impactful because the genetic code is read in triplets, known as codons, during translation. When the reading frame is altered—due to the addition or deletion of nucleotides that do not maintain this triplet structure—every subsequent codon is shifted. This leads to a completely different translation downstream of the mutation. The result can be the production of a nonfunctional protein or an entirely different set of amino acids, which can significantly impact the organism's phenotype.

Factors making frame-shift mutations significant include their potential to create premature stop codons, resulting in truncated proteins, or to change the protein's structure and function dramatically. In contrast, point mutations only involve the alteration of a single nucleotide, so they do not alter the reading frame of the mRNA. Silent mutations do not affect the amino acid sequence, and missense mutations change one amino acid to another but do not shift the reading frame. Thus, the nature of frame-shift mutations lies in their disruptive capability caused by incorrect codon alignment following the mutation.