One sequence, two ribozymes: Implications for the emergence of new ribozyme folds

We describe a single RNA sequence that can assume either of two ribozyme fo lds and catalyze the two respective reactions. The two ribozyme fords share no evolutionary history and are completely different, with no base pairs r and probably no hydrogen bonds) in common, Minor variants of this sequence are highly active for one or the other reaction, and can be accessed from p rototype ribozymes through a series of neutral mutations. Thus, in the cour se of evolution, new RNA folds could arise from preexisting folds, without the need to carry inactive intermediate sequences. This raises the possibil ity that biological RNAs having no structural or functional similarity migh t share a common ancestry. Furthermore, functional and structural divergenc e might, in some cases, precede rather than follow gene duplication.