frameshift

Frameshift is a genetic alteration that changes the reading frame of a gene or, in translation, a regulatory shift during protein synthesis. In coding sequences, codons are read as consecutive triplets. An insertion or deletion of one or two nucleotides shifts this frame downstream of the mutation, causing a new sequence of amino acids to be produced and most often introducing a premature stop codon. Indels that are multiples of three nucleotides change the encoded amino acids without altering the reading frame; these are called in-frame indels.

The downstream impact of a frameshift is typically severe. The altered amino acid sequence usually disrupts the protein’s structure and function, and premature termination commonly yields a truncated, nonfunctional protein. Nonsense-mediated decay may reduce the amount of the mutant mRNA, further diminishing protein production. The exact effect depends on the gene, the mutation’s location, and the structural tolerance of the resulting protein.

Frameshifting is also exploited as a regulatory mechanism in some organisms. Programmed ribosomal frameshifting, found in certain viruses and genetic elements, deliberately alters the reading frame (often by −1 or +1 shifts) during translation to control the production of multiple proteins from a single RNA.

In research and medicine, frameshift mutations are important because they are a common cause of genetic diseases and cancers. They are also a common target in genome editing approaches that disrupt gene function by introducing frameshifts.