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Updated: Sep 6, 2025

Curation of Computational Chemical Libraries Demonstrated with Alpha-Amino Acids
Published on: April 13, 2022
Emergent properties as by-products of prebiotic evolution of aminoacylation ribozymes
Evan Janzen1,2, Yuning Shen2,3, Alberto Vázquez-Salazar3
1Program in Biomolecular Science and Engineering, University of California, Santa Barbara, CA, 93106, USA.
Abstract:
Systems of catalytic RNAs presumably gave rise to important evolutionary innovations, such as the genetic code. Such systems may exhibit particular tolerance to errors (error minimization) as well as coding specificity. While often assumed to result from natural selection, error minimization may instead be an emergent by-product. In an RNA world, a system of self-aminoacylating ribozymes could enforce the mapping of amino acids to anticodons. We measured the activity of thousands of ribozyme mutants on alternative substrates (activated analogs for tryptophan, phenylalanine, leucine, isoleucine, valine, and methionine). Related ribozymes exhibited shared preferences for substrates, indicating that adoption of additional amino acids by existing ribozymes 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 ribozyme evolution could lead to adaptive value in specificity and error tolerance.
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