Although the decoding rules have been largely elucidated,
the physical-chemical reasons for the “correctness”
of codon:anticodon duplexes have never been clear. In this
work, on the basis of the available data, we propose that
the correct codon:anticodon duplexes are those whose formation
and interaction with the ribosomal decoding center are
not accompanied by uncompensated losses of hydrogen and
ionic bonds. Other factors such as proofreading, base–base
stacking and aminoacyl–tRNA concentration contribute
to the efficiency and accuracy of aminoacyl–tRNA
selection, and certainly these factors are important; but
we suggest that analyses of hydrogen and ionic bonding
alone provides a robust first-order approximation of decoding
accuracy. Thus our model can simplify predictions about
decoding accuracy and error. The model can be refined with
data, but is already powerful enough to explain all of
the available data on decoding accuracy. Here we predict
which duplexes should be considered correct, which duplexes
are responsible for virtually all misreading, and we suggest
an evolutionary scheme that gave rise to the mixed boxes
of the genetic code.