From Sequences to Shapes and Back: A Case Study in RNA Secondary Structures

• Published in: Proceedings of the Royal Society. B, Biological sciences Biological sciences, 1994-03, Vol.255 (1344), p.279-284
• Main Authors: Schuster, Peter, Fontana, Walter, Stadler, Peter F., Hofacker, Ivo L.
• Format: Article
• Language: English
• Subjects: Base Composition; Base Sequence; Biological and medical sciences; Evolution; Fundamental and applied biological sciences. Psychology; Genetic mutation; Geometric shapes; Hamming distances; Models, Structural; Molecular biophysics; Molecular chains; Molecular structure; Molecules; Nucleic Acid Conformation; Nucleotide sequences; Nucleotides; RNA; RNA - chemistry; Structure in molecular biology; Thermodynamics; Tridimensional structure
• ISSN: 0962-8452; 1471-2954
• DOI: 10.1098/rspb.1994.0040

RNA folding is viewed here as a map assigning secondary structures to sequences. At fixed chain length the number of sequences far exceeds 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. By using an algorithm for inverse folding, we show that sequences sharing the same structure are distributed randomly 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 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.