FROM SEQUENCES TO SHAPES AND BACK - A CASE-STUDY IN RNA SECONDARY STRUCTURES

RNA folding is viewed here as a map assigning secondary structures to sequences. At fixed chain length the number of sequences far exceeds t he number of structures. Frequencies of structures are highly non-unif orm and follow a generalized form of Zipf's law: we find relatively fe w common and many rare ones. By using an algorithm for inverse folding , we show that sequences sharing the same structure are distributed ra ndomly over sequence space. All common structures can be accessed from an arbitrary sequence by a number of mutations much smaller than the chain length. The sequence space is percolated by extensive neutral ne tworks connecting nearest neighbours folding into identical structures . Implications for evolutionary adaptation and for applied molecular e volution are evident: finding a particular structure by mutation and s election is much simpler than expected and, even if catalytic activity should turn out to be sparse in the space of RNA structures, it can h ardly be missed by evolutionary processes.