title: Selection of new biological activities from random nucleotide sequences: evolutionary and practical considerations.
abstract: Recent advances in the selection of biologically active DNA sequences from random populations are reviewed. Within the framework of evolution, forces are considered that have precluded the testing of all possible DNA sequences, purely with regard to their functionality as genetic regulatory elements or protein coding sequences. Examples are drawn from cassette mutagenesis of enzyme active sites, protein domain replacement by fusion with random genomic digests, and the selection of bacterial promoters from random DNA. Efforts to derive new activities are examined, and the likelihood of future success is evaluated.
authors.affiliation: Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle 98195.
authors.forename: M S
authors.initials: MS
authors.lastname: Horwitz
authors.forename: D K
authors.initials: DK
authors.lastname: Dube
authors.forename: L A
authors.initials: LA
authors.lastname: Loeb
mesh_terms: D001483:Base Sequence; D005075:Biological Evolution; D012321:DNA-Directed RNA Polymerases / Q000502:physiology; D004798:Enzymes / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D004798:Enzymes; D012321:DNA-Directed RNA Polymerases