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Annu Rev Genet. 2017 Nov 27;51:45-62. doi: 10.1146/annurev-genet-120116-024713. Epub 2017 Aug 30.

Origin and Evolution of the Universal Genetic Code.

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National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA; email:
Department of Mathematics, North Dakota State University, Fargo, North Dakota 58108, USA.


The standard genetic code (SGC) is virtually universal among extant life forms. Although many deviations from the universal code exist, particularly in organelles and prokaryotes with small genomes, they are limited in scope and obviously secondary. The universality of the code likely results from the combination of a frozen accident, i.e., the deleterious effect of codon reassignment in the SGC, and the inhibitory effect of changes in the code on horizontal gene transfer. The structure of the SGC is nonrandom and ensures high robustness of the code to mutational and translational errors. However, this error minimization is most likely a by-product of the primordial code expansion driven by the diversification of the repertoire of protein amino acids, rather than a direct result of selection. Phylogenetic analysis of translation system components, in particular aminoacyl-tRNA synthetases, shows that, at a stage of evolution when the translation system had already attained high fidelity, the correspondence between amino acids and cognate codons was determined by recognition of amino acids by RNA molecules, i.e., proto-tRNAs. We propose an experimentally testable scenario for the evolution of the code that combines recognition of amino acids by unique sites on proto-tRNAs (distinct from the anticodons), expansion of the code via proto-tRNA duplication, and frozen accident.


aminoacyl–tRNA synthetases; anticodons; codons; coevolution theory; error minimization; evolution of translation; frozen accident; standard genetic code; stereochemical theory; universal genetic code

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