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J Biol Phys. 2002 Sep;28(3):471-82. doi: 10.1023/A:1020345530127.

Molecular evolution in static and dynamical landscapes.


In an attempt to understand protein evolution, we address the issues ofhow much variety in the sequences is needed to prompt the evolution ofan enzyme from random polypeptides and how does cellular interactionaffect the dynamics of molecular evolution to allow genetic diversity inpopulation. The experimental evolution of phage-displayed randompolypeptides of about 140 amino acid residues panned with transition stateanalogue for an esterase reaction showed that even with a population sizeas small as ten, not only could significant varieties be found but also therandom polypeptides in each of the generation had great promise towardsdeveloping into functional proteins. Hence, it is evident that the enzymeevolution is prompted even within a small local area of the static landscapeof the sequence space. Considering that interaction among living cells is aninevitable event in natural evolution, its role was investigated through threeconsecutive rounds of random mutagenesis on the glutamine synthetasegene and chemostat culture of the transformed Escherichia colicellscontaining the mutated genes. The molecular phylogeny and populationdynamics show the coexistence of some mutants having different level ofglutamine synthetase at each generation. In addition, it was confirmed thatcellular interaction via the medium influences the stability of the coexistenceand bring forth fitness change to the coexisting members of the population,thereby, leading to a dynamical landscape. Based on experimental resultsreflecting the extent of interaction among members in population, here, Iproposed that protein evolution could change its mode from theoptimization on static landscape to diversification on dynamicallandscape.


cellular interaction; diversification; fitness landscape; library size; optimization; protein evolution; sequence space

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