Review
Selection, history and chemistry: the three faces of the genetic code

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Abstract

The genetic code might be a historical accident that was fixed in the last common ancestor of modern organisms. ‘Adaptive’, ‘historical’ and ‘chemical’ arguments, however, challenge such a ‘frozen accident’ model. These arguments propose that the current code is somehow optimal, reflects the expansion of a more primitive code to include more amino acids, or is a consequence of direct chemical interactions between RNA and amino acids, respectively. Such models are not mutually exclusive, however. They can be reconciled by an evolutionary model whereby stereochemical interactions shaped the initial code, which subsequently expanded through biosynthetic modification of encoded amino acids and, finally, was optimized through codon reassignment. Alternatively, all three forces might have acted in concert to assign the 20 ‘natural’ amino acids to their present positions in the genetic code.

Section snippets

Adaptation – the best of all possible codes?

The earliest explanations for the observed order in the genetic code, such as Crick’s ingenious commaless code3, assumed that natural selection somehow optimized the codon catalog. Given that more changes to a protein are deleterious than beneficial, the genetic code should reduce the impact of errors: the pattern of degeneracy, which groups together codons for the same amino acid, certainly has this effect (Fig. 1). The ‘lethal mutation’ model4 proposed that the genetic code reduces the

History – searching for footprints of the code’s ancestors

Historical theories propose that the present code evolved from a simpler ancestral form: proteins produced by the initial, limited, set of amino acids synthesized new amino acids that could in turn be incorporated into the code. Recently introduced amino acids presumably would take over codons from their metabolic precursors; this could happen only if the resulting changes in protein structure were not widely deleterious2. Consequently, historical theories often predict that similar amino acids

Stereochemistry – does it fit the evidence?

Stereochemical theories propose that amino acids are assigned to particular codons because of direct chemical interactions between RNA and amino acids. If these interactions follow consistent patterns, similar amino acids should bind to similar short RNA motifs and should therefore have similar codons. Although the resulting pattern of codon assignments might be adaptive, relative to randomized codes (because a point mutation would tend to substitute a relatively similar amino acid), it need

The RNA world: the milieu of code evolution?

Translation presents a ‘chicken or egg’ problem: given that many crucial components of the translation apparatus (including aminoacyl-tRNA synthetases, release factors and much of the ribosome) are made of protein, how could translation ever have evolved? The RNA-world hypothesis44 avoids this problem by suggesting that RNA preceded DNA and protein and acted as both genetic material and catalyst. The structure of the genetic code might contain information about the chemical environment in which

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