Schimmel Lab - The Scripps Research Institute

We are examining the origin and early evolution of the genetic code. RNA minihelices were found to be aminoacylated in vitro based on simple base pairing rules. This system is used as a model for the early transition
from the RNA World to the Theater of Proteins. We have shown that this system can be singly and multiply aminoacylated. Furthermore, this system is chiroselective, and indicates that D-sugars are selective for L-amino
acids. In order to examine a later stage in the evolution of the genetic code, bacterial strains have been constructed that lack the editing capability of aminoacyl-tRNA synthetases. This serves as a model of the period in which the genetic code was expanding, and was likely to have been ambiguous. We have found that extant organisms are generally growth-inhibited by an ambiguous genetic code. However, under certain conditions amino acid analogs can supplement growth of these editing-deficient organisms. We are continuing to investigate the extent to which growth can be supplemented by genetic code ambiguity, as well as the evolutionary adaptation of organisms to conditions of genetic code ambiguity.