Structure and evolution of the genetic code viewed from the perspective ofthe experimentally expanded amino acid repertoire in vivo

Much effort has been devoted recently to expanding the amino acid repertoir e in protein biosynthesis in vivo. From such experimental work it has emerg ed that some of the non-canonical amino acids are accepted by the cellular translational machinery while others are not, i.e. we have learned that som e determinants must exist and that they can even be anticipated. Here, we p ropose a conceptual framework by which it should be possible to assess deep er levels of the structure of the genetic code, and based on this experimen t to understand its evolution and establishment. First, we propose a standa rdised repertoire of 20 amino acids as a basic set of conserved building bl ocks in protein biosynthesis in living cells to be the main criteria for ge netic code structure and evolutionary considerations. Second, based on such argumentation, we postulate the structure and evolution of the genetic cod e in the form of three general statements: (i) the nature of the genetic co de is deterministic; (ii) the genetic code is conserved and universal; (iii ) the genetic code is the oldest known level of complexity in the evolution of living organisms that is accessible to our direct observation and exper imental manipulations. Such statements are discussed as our working hypothe ses that are experimentally tested by recent findings in the held of expand ed amino acid repertoire in vivo.