The effects on a reading frame of combining insertion and deletion mutations. Insertion or deletion of a single nucleotide throws the ribosome into the wrong reading frame and produces a mutant protein (amino acids shown in red). (a) The wild-type protein sequence. (b) The effect of an insertion mutation. (c) The effect of a deletion mutation. (d) Combining an insertion and a deletion affects some amino acids but eventually restores the correct sequence. (e) Combining three consecutive insertion mutations (or three deletions) leaves the remaining triplets intact—evidence that a codon has three, rather than four or five, nucleotides.