Evolutionary biotechnology

The theory of molecular evolution and the in vitro evolution experiments suggest practical applications to the design of biopolymer molecules as they were proposed already in the 1980s [4], The basic principles of the so-called irrational design of biomolecules are indeed identical with Darwin s natural law of variation and selection. Molecular properties are improved iteratively in selection cycles in order to achieve an optimal match with the predefined target function. The process is sketched in Fig. 5. Every selection cycle consists of three phases amplification, diversification, and selection. In these experiments, the fitness of genotypes is tantamount to their probability to enter the next selection round. 

Information on various parameters is required in order to make evolutionary design of biomolecules efficient. There are, for example, population sizes, amplification factors, mutation rates, reaction volumes, and many other factors that strongly influence the outcome and the efficiency of an evolution experiment. The individual parameters are not independent and therefore simple estimates based on uncorrelated superposition are likely to be incorrect. The model introduced earlier in this chapter allows to implement computer simulations that are suitable to clarify the role of individual parameters and to provide estimates on the optimal choices. 

Amplification and diversification can be achieved in different ways by the current techniques of molecular biology. Several efficient replication assays are available for DNA 

RNA secondary structures provide a kind of toy universe that allows to study the mapping of genotypes into molecular phenotypes in great detail. Three global relations between RNA sequences and structures were found to be important for evolution  

We were able to show that these three properties related to neutrality with respect to selection make evolution of RNA molecules for predefined purposes a much simpler problem than previously thought. 

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Eigen M and Rigler R 1994 Sorting single molecules application to diagnostics and evolutionary biotechnology Proc. Natl Acad. Sc/. USA 91 5740-7... 

Eigen, M. and Rigler, R. (1994). Sorting single molecules Applications to diagnostics and evolutionary biotechnology. Proc. Natl. Acad. Sci. USA 91, 5740-9. 

The desire to create RNA molecules with predefined properties and to optimize their efficiencies and specificities has led to a new technique called evolutionary biotechnology or applied molecular evolution. Natural selection or its analogue in test-tube evolution optimizes fitness or replication rate constants, respectively. High replication rates, however, are neither required nor wanted in the search for... 

Evolutionary Biotechnology - From Ideas and Concepts to Experiments and Computer Simulations... 

Molecular impurities in solids can now be detected down to the singlemolecule level [15.16]. These molecules and their interaction with their surroundings can be probed by high-resolution laser spectroscopy. The relevance of such techniques in biology is obvious [15.17]. The development of single-molecule detection for the in vitro and in vivo quantification of biomolecular dynamics is essential for the understanding of biomolecular reactions and for the realization of evolutionary biotechnology [15.18]. 

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