Trends in Biochemical Sciences
ReviewSelection, history and chemistry: the three faces of 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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