GENETIC-CODE IN EVOLUTION - SWITCHING SPECIES-SPECIFIC AMINOACYLATIONWITH A PEPTIDE TRANSPLANT

The genetic code is established in aminoacylation reactions whereby am ino acids are joined to tRNAs bearing the anticodons of the genetic co de, Paradoxically, while the code is universal there are many examples of species-specific aminoacylations, where a tRNA from one taxonomic domain cannot be acylated by a synthetase from another. Here we consid er an example where a human, but not a bacterial, tRNA synthetase char ges its cognate eukaryotic tRNA and where the bacterial, but not the h uman, enzyme charges the cognate bacterial tRNA. While the bacterial e nzyme has less than 10% sequence identity with the human enzyme, trans plantation of a 39 amino acid peptide from the human into the bacteria l enzyme enabled the latter to charge its eukaryotic tRNA counterpart in vitro and in vivo, Conversely, substitution of the corresponding pe ptide of the bacterial enzyme for that of the human enabled the human enzyme to charge bacterial tRNA, This peptide element discriminates a base pair difference in the respective tRNA acceptor stems, Thus, func tionally important co-adaptations of a synthetase to its tRNA act as s mall modular units that can be moved across taxonomic domains and ther eby preserve the universality of the code.