Folding both ways

In the 21 July Science, Schultes and Bartel describe a single RNA sequence that can fold to form two structurally unrelated but catalytically active ribozymes (Science 2000, 289:448-452). They start with the RNA-cleaving ribozyme from hepatitis delta virus (HDV) and an artificial RNA ligase. The two ribozymes use unrelated catalytic mechanisms and have no more sequence similarity than would be expected by chance. But an 'intersection' sequence can be derived that preserves the base-pairing for both structures, and leaves the two catalytic activities intact. Schultes and Bartel also describe pathways by which the intersection sequence can be slowly modified to the sequence of either of the wildtype (mono-catalytic) ribozymes, with minimal loss of target enzymatic activity at any step. Thus divergence of function may precede rather than follow gene duplication, and RNAs with no structural or functional similarity may share an ancestor.