Landscapes Complex Optimization Problems and Biopolymer Structures

Peter Schuster and Peter F. Stadler

The evolution of RNA molecules in replication assays, viroids and RNA viruses can be viewed as an adaptation process on a ``fitness'' landscape. The dynamics of evolution is hence tightly linked to the structure of the underlying landscape. Global features of landscapes can be described by statistical measures like number of optima, lengths of walks, and correlation functions. The evolution of a quasispecies on such landscapes exhibits three dynamical regimes depending on the replication fidelity: Above the``localization threshold'' the population is centered around a (local) optimuim. Between localization and ``dispersion threshold'' the population is still centered around a consensus sequence, which, however, changes in time. For very large mutation rates the population spreads in squence space like a gas. The critical mutation rates separating the three domains depend strongly on characteristics properties of the fitness landscapes. Statistical characteristics of RNA landscapes are accesssibly by mathematical analysis and computer calculations on the level of secondary structures: these RNA landscapes belong to the same class as well known optimization problems and simple spin glass models. The notion of a landscapes is extended to combinatory maps, thereby allowing for a direct statistical investigation of the sequence structure relationships of RNA at the level of secondary structures. Frequencies of structures are highly non-uniform: we find relatively few common and many rare ones, as expressed by a generalized form of Zipf's law. Using an algorithm for inverse folding we show that sequences sharing the same structure are distributed randomly over sequence space. Together with calculations of structure correlations and a survey of neutral mutations this provides convincing evidence that RNA landscapes are as simple as they could possibly be for evolutionary adaptation: Any desired secondary structure can be found close to an arbitrary intitial sequence and at the same time almost all bases can be substituted sequentially without ever changing the shape of the molecule. Consequences of these results for the evolutionary optimization, the early stages of life, and molecular biotechnology are discussed.

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