P. Schuster, W. Fontana, P. F. Stadler and I. Hofacker
RNA folding is viewed here as a map assigning secondary structures to sequences. At fixed chain length the number of sequences exceeds by far the number of structures. Frequencies of structures are highly non-uniform and follow a generalized form of Zipf's law: we find relatively few common and many rare ones. Using an algorithm for inverse folding we show that sequences sharing the same structure are distributed randomly over sequence sapce. 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 networks connecting nearest neighbours folding into identical structures. Implications for evolutionary adaptation and for applied molecular evolution are evident: finding a particular structure by mutation and selection is much simpler than expected, and even if catalytic activity should turn out to be sparse in the space of RNA structures, it can hardly be missed by evolutionary processes