The 'evolvability' of promiscuous protein functions

Nat Genet. 2005 Jan;37(1):73-6. doi: 10.1038/ng1482. Epub 2004 Nov 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryldialkylphosphatase / genetics*
  • Aryldialkylphosphatase / physiology
  • Bacteria / enzymology
  • Bacteria / genetics
  • Carbonic Anhydrase II / genetics*
  • Carbonic Anhydrase II / physiology
  • Evolution, Molecular*
  • Genetic Variation
  • Humans
  • Phosphoric Triester Hydrolases / genetics*
  • Phosphoric Triester Hydrolases / physiology
  • Polymerase Chain Reaction
  • Protein Structure, Tertiary


  • Phosphoric Triester Hydrolases
  • Aryldialkylphosphatase
  • Carbonic Anhydrase II