BackgroundThe origins of life on the Earth required chemical entities to interact with their environments in ways that could respond to natural selection. The concept of interpretation, where biotic entities use signs in their environment as proxy for the existence of other items of selective value in their environment, has been proposed on theoretical grounds to be relevant to the origins and early evolution of life. However this concept has not been demonstrated empirically.ResultsHere, we present data that certain catalytic RNA sequences have properties that would enable interpretation of divalent cation levels in their environment. By assaying the responsiveness of two variants of the Tetrahymena ribozyme to the Ca2+ ion as a sign for the more catalytically useful Mg2+ ion, we show an empirical proof-of-principle that interpretation can be an evolvable trait in RNA, often suggested as a model system for early life. In particular we demonstrate that in vitro, the wild-type version of the Tetrahymena ribozyme is not interpretive, in that it cannot use Ca2+ as a sign for Mg2+. Yet a variant of this sequence containing five mutations that alter its ability to utilize the Ca2+ ion engenders a strong interpretive characteristic in this RNA.ConclusionsWe have shown that RNA molecules in a test tube can meet the minimum criteria for the evolution of interpretive behaviour in regards to their responses to divalent metal ion concentrations in their environment. Interpretation in RNA molecules provides a property entirely dependent on natural physico-chemical interactions, but capable of shaping the evolutionary trajectory of macromolecules, especially in the earliest stages of life¿s history.