Emergent Properties as By-products of Prebiotic Evolution of Aminoacylation Ribozymes

The emergence of the genetic code was a major transition in the evolution from a prebiotic RNA world to the earliest modern cells. A prominent feature of the standard genetic code is error minimization, or the tendency of mutations to be unusually conservative in preserving biophysical features of the amino acid. While error minimization is often assumed to result from natural selection, it has also been speculated that error minimization may be a by-product of emergence of the genetic code. During establishment of the genetic code in an RNA world, self-aminoacylating ribozymes would enforce the mapping of amino acids to anticodons. Here we show that expansion of the genetic code, through co-option of ribozymes for new substrates, could result in error minimization as an emergent property. Using self-aminoacylating ribozymes previously identified during an exhaustive search of sequence space, we measured the activity of thousands of candidate ribozymes on alternative substrates (activated analogs for tryptophan, phenylalanine, leucine, isoleucine, valine, and methionine). Related ribozymes exhibited preferences for biophysically similar substrates, indicating that co-option of existing ribozymes to adopt additional amino acids into the genetic code would itself lead to error minimization. Furthermore, ribozyme activity was positively correlated with specificity, indicating that selection for increased activity would also lead to increased specificity. These results demonstrate that by-products of the evolution and functional expansion of the ribozyme system would lead to apparently adaptive properties of the genetic code.

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Methods
Data were collected from k-Seq experiments using methods similar to those described in two of the supplementary articles linked to this deposit (https://doi.org/10.1021/jacs.8b13298) and (https://doi.org/10.1093/nar/gkab199/6194417) using BWO, BFO, BLO, BIO, BVO, or BMO as substrates for aminoacylating ribozymes.

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