The biological role of RNA is delimited by its possible reactions, whi
ch can be explored by selection. A comparison of selected RNAs that bi
nd one ligand with those that bind two related ligands suggests that a
single nucleotide substitution can expand binding specificity. An RNA
site with dual (joint) specificity has adenine and cytosine bases who
se pK(a)'s appear shifted upward, thereby mimicking an efficient gener
al acid-base catalyst. The joint site also contains two conserved, loo
ped arginine-coding triplets implicated in arginine site formation. Tw
o selected joint RNAs are identical in some regions and distinct in ot
hers. The distinct regions, like some peptides, seem to function simil
arly without being similar in primary structure.