Open AccessFunctionally diverging molecular quasi-species evolve by crossing two enzymes
Author(s) -
Lars O. Emrén,
Sanela Kurtovic,
Arna Rúnarsdóttir,
AnnaKarin Larsson,
Bengt Mannervik
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0604030103
Subject(s) - biology , phenotype , molecular evolution , enzyme , genetics , mutant , computational biology , principal component analysis , substrate specificity , dna , biochemistry , evolutionary biology , gene , phylogenetics , artificial intelligence , computer science
Molecular evolution is frequently portrayed by structural relationships, but delineation of separate functional species is more elusive. We have generated enzyme variants by stochastic recombinations of DNA encoding two homologous detoxication enzymes, human glutathione transferases M1–1 and M2–2, and explored their catalytic versatilities. Sampled mutants were screened for activities with eight alternative substrates, and the activity fingerprints were subjected to principal component analysis. This phenotype characterization clearly identified at least three distributions of substrate selectivity, where one was orthogonal to those of the parent-like distributions. This approach to evolutionary data mining serves to identify emerging molecular quasi-species and indicates potential trajectories available for further protein evolution.