Determining the evolutionary potential of a gene.
In addition to information for current functions, the sequence of a gene includes potential information for the evolution of new functions. The wild-type ebgA (evolved beta-galactosidase) gene of Escherichia coli encodes a virtually inactive beta-galactosidase, but that gene has the potential to evolve sufficient activity to replace the lacZ gene for growth on the beta-galactoside sugars lactose and lactulose. Experimental evidence, which has suggested that the evolutionary potential of Ebg enzyme is limited o two specific amino acid replacements, is limited to examining the consequences of single base-substitutions. Thirteen beta-galactosidases homologous with the Ebg beta-galactosidase are widely dispersed, being found in gram-negative and gram-positive eubacteria and in a eukaryote. A comparison of Ebg beta-galactosidase with those 13 beta-galactosidases shows that Ebg is part of an ancient clade that diverged from the paralogous lacZ beta-galactosidase over 2 billion years ago. Ebg differs from other members of its clade at only 2 of the 15 active-site residues, and the two mutations required for full Ebg beta-galactosidase activity bring Ebg into conformity with the other members of its clade. We conclude that either these are the only acceptable amino acids at those positions, or all of the single-base-substitution replacements that must arise as intermediates on the way to other acceptable amino acids are so deleterious that they constitute a deep selective valley that has not been traversed in over 2 billion years. The evolutionary potential of Ebg is thus limited to those two replacements.
Biology Department, University of Rochester, New York 14627. drbh@uhura.cc.rochester.edu
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D007763:Lac Operon; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D001616:beta-Galactosidase / Q000235:genetics
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D001616:beta-Galactosidase; C062846:evolved beta-galactosidase, E coli