Reading frame

A reading frame specifies how consecutive nucleotides are grouped into codons. Starting at position 1 of AUGGCUUAA gives AUG / GCU / UAA; starting at position 2 gives UGG / CUU with AA left over. The letters are unchanged but the groups differ. A possible grouping alone does not establish an actual biological translation initiation site.

For the twelve-nucleotide example, number positions from the $5^{\prime }$ end. The three possible forward reading frames start at positions 1, 2 and 3:Parentheses enclose incomplete trailing groups. The second and third rows do not assert initiation of biological translation in a biological cell. A chosen start fixes which positions belong together; the ribosome then advances through consecutive codons rather than searching each three-letter window independently.

A sequence interpreted in a particular codon frame without an internal in-frame stop, with the boundary convention stated. Prediction of an open reading frame alone does not demonstrate biological translation or a stable functional product.

A relatively short potential coding region under an explicitly chosen length convention. Evidence of biological translation and evidence for a stable functional peptide are different.

A change of reading frame during biological translation. It need not change the underlying DNA sequence, unlike a frameshift mutation. It can be programmed by a recoding signal or occur as a translation error.

Programmed ribosomal frameshifting changes the reading frame during translation at a specific recoding signal. A slippery sequence and a downstream RNA structure can bias the event, allowing one transcript to produce different polypeptides in controlled proportions.

A frameshift mutation changes downstream grouping into codons through insertion or deletion of a number of nucleotides not divisible by three. In the constructed messenger RNA example, insert C immediately after AUG while retaining the same initiation position: $\mathrm{AUG}\mathrm{CGC}\mathrm{UUU}\mathrm{CUG}(\mathrm{A})$. The first codon is preserved, but the original downstream groups GCU, UUC and UGA disappear. The displayed fragment now has no complete standard stop codon; what happens later depends on its continuation.

The short proof is positional: every downstream nucleotide moves by $k$ positions after an insertion of length $k$. Boundaries recur every three positions, so they retain the original phase exactly when $k$ is divisible by three. An insertion of three nucleotides can still change the peptide, but it does not shift the downstream reading frame. This distinction helps interpret genetic variants without predicting a particular phenotype from grouping alone.^[ref]