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Selection of new biological activities from random nucleotide sequences: evolutionary and practical considerations
M S Horwitz1, D K Dube, L A Loeb
1Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle 98195.
Genome
|January 1, 1989
Summary
Researchers review methods for selecting functional DNA sequences from random populations. Evolution limits exhaustive testing, but techniques like cassette mutagenesis and promoter selection show promise for discovering new genetic elements.
Area of Science:
- Molecular Biology
- Genetics
- Evolutionary Biology
Background:
- Selecting biologically active DNA sequences from large, random populations is crucial for understanding gene function and engineering novel biological systems.
- Evolutionary constraints and the sheer scale of possible DNA sequences limit the comprehensive empirical testing of all potential genetic elements.
Purpose of the Study:
- To review recent advancements in selecting functional DNA sequences from random pools.
- To examine the evolutionary forces that restrict the exhaustive exploration of DNA sequence space for genetic regulatory elements and protein-coding sequences.
- To evaluate the potential for deriving new biological activities through these selection methods.
Main Methods:
- Review of literature on selection strategies for biologically active DNA.
- Analysis of evolutionary principles impacting the feasibility of testing all DNA sequences.
- Examples include cassette mutagenesis of enzyme active sites, protein domain fusion with random genomic fragments, and selection of bacterial promoters from random DNA libraries.
Main Results:
- Recent techniques enable the selection of functional DNA sequences with specific biological activities from diverse random populations.
- The review highlights successful applications in enzyme engineering and the identification of regulatory elements.
- The inherent limitations imposed by evolutionary processes are discussed in the context of discovering novel DNA functionalities.
Conclusions:
- Despite evolutionary constraints, advanced selection methods offer powerful tools for discovering and engineering biologically active DNA sequences.
- Future efforts in deriving new activities are promising, with ongoing technological advancements.
- The study evaluates the likelihood of continued success in identifying novel genetic regulatory elements and protein-coding sequences.