The balance of evidence both from the cell-free system and from the study of mutation, suggests that this does not occur at random, and that triplets coding the same amino acid may well be rather similar.

For simplicity one can think of the + class as having one extra base at some point or other in the genetic message and the - class as having one too few.

How is the base sequence, divided into codons? There is nothing in the backbone of the nucleic acid, which is perfectly regular, to show us how to group the bases into codons.

Francis Crick Quotes