frameshifts

Frameshifts are genetic mutations in which the addition or removal of one or two nucleotides shifts the reading frame of a gene. Because codons are read in triplets, any insertion or deletion not in multiples of three changes every downstream codon, typically producing a cascade of altered amino acids and often a premature stop codon.

Causes include errors during DNA replication, repair, and recombination, or insertion of transposable elements. Slippage of DNA polymerase in repetitive sequences is a common source of frameshift indels. Frameshifts can also result from viral integration or exposure to mutagens that cause insertions or deletions.

Consequences are usually severe for the encoded protein. The altered reading frame commonly yields a nonfunctional protein and may trigger nonsense-mediated decay of the mRNA in eukaryotes if a premature termination codon is introduced. In some cases, frameshifts near the end of a gene partially preserve function.

A related concept is in-frame mutations, where the number of nucleotides inserted or deleted is a multiple of three. Such changes add or remove amino acids without shifting downstream codons and therefore do not disrupt the overall reading frame.

Detection and repair: Frameshift mutations are identified by DNA sequencing and alignment to reference sequences. Cellular repair systems, including mismatch repair and other repair pathways, can correct indels in some cases; if not repaired, the frameshift is inherited by progeny during cell division.