Which mutation is most likely to lead to severe changes in protein function?

A frameshift mutation is likely to lead to severe changes in protein function due to the way it alters the reading frame of the genetic code. When a frameshift mutation occurs, whether through the insertion or deletion of nucleotides, it changes how the nucleotides are grouped into codons during translation. This shift affects all downstream amino acids, often resulting in an entirely different protein sequence, which can lead to a nonfunctional protein or one with drastically altered activity.

This contrasts with point mutations, which typically only result in the alteration of a single amino acid within the protein. While this can affect protein function, especially if the amino acid is critical for activity, the overall structure and function of the protein may still remain largely intact. Silent mutations, on the other hand, do not change the amino acid sequence due to the redundancy in the genetic code; thus, they typically have no impact on protein function. Missense mutations can also alter a single amino acid, potentially affecting the protein, but generally not to the severe extent of a frameshift mutation that disturbs the entire translation reading frame.