title: Protein building blocks preserved by recombination.
abstract: Borrowing concepts from the schema theory of genetic algorithms, we have developed a computational algorithm to identify the fragments of proteins, or schemas, that can be recombined without disturbing the integrity of the three-dimensional structure. When recombination leaves these schemas undisturbed, the hybrid proteins are more likely to be folded and functional. Crossovers found by screening libraries of several randomly shuffled proteins for functional hybrids strongly correlate with those predicted by this approach. Experimental results from the construction of hybrids of two beta-lactamases that share 40% amino acid identity demonstrate a threshold in the amount of schema disruption that the hybrid protein can tolerate. To the extent that introns function to promote recombination within proteins, natural selection would serve to bias their locations to schema boundaries.
authors.affiliation: Biochemistry and Molecular Biophysics, California Institute of Technology, mail code 210-41, Pasadena, California 91125, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Voigt
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez
authors.forename: Zhen-Gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Mayo
authors.forename: Frances H
authors.initials: FH
authors.lastname: Arnold
mesh_terms: D000465:Algorithms; D000667:Ampicillin / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D007438:Introns / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012641:Selection, Genetic; D016415:Sequence Alignment; D012984:Software; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D011993:Recombinant Fusion Proteins; D000667:Ampicillin; D001618:beta-Lactamases