title: The 'evolvability' of promiscuous protein functions.
abstract: How proteins with new functions (e.g., drug or antibiotic resistance or degradation of man-made chemicals) evolve in a matter of months or years is still unclear. This ability is dependent on the induction of new phenotypic traits by a small number of mutations (plasticity). But mutations often have deleterious effects on functions that are essential for survival. How are these seemingly conflicting demands met at the single-protein level? Results from directed laboratory evolution experiments indicate that the evolution of a new function is driven by mutations that have little effect on the native function but large effects on the promiscuous functions that serve as starting point. Thus, an evolving protein can initially acquire increased fitness for a new function without losing its original function. Gene duplication and the divergence of a completely new protein may then follow.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Aharoni
authors.forename: Leonid
authors.initials: L
authors.lastname: Gaidukov
authors.forename: Olga
authors.initials: O
authors.lastname: Khersonsky
authors.forename: Stephen
authors.initials: S
authors.lastname: McQ Gould
authors.forename: Cintia
authors.initials: C
authors.lastname: Roodveldt
authors.forename: Dan S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000502:physiology; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D024402:Carbonic Anhydrase II / Q000235:genetics* / Q000502:physiology; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D044345:Phosphoric Triester Hydrolases / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary
chemical_list: D044345:Phosphoric Triester Hydrolases; D043303:Aryldialkylphosphatase; D024402:Carbonic Anhydrase II