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Abstract

The emergence of catalytic RNAs (ribozymes) may have set the stage for an “RNA world” preceding protein evolution. The probability of ribozyme emergence and maintenance would have depended on available oligonucleotide compositions. Excessively high or low sequence diversity could hinder ribozyme formation, whereas balanced diversity is likely more favorable. Multiple steps of chemical evolution—from nucleotide supply and oligomerization to subsequent copying and assembly through nonenzymatic reactions—likely shaped oligonucleotide diversity. In this review, we discuss how oligonucleotide chemical evolution may have involved both selective enrichment and diversification of sequence compositions, with their interplay generating oligonucleotide pools of varying diversity across environments and evolutionary timescales. Current experiments on nonenzymatic RNA-based reactions remain limited to short timescales, but strategies combining DNA and protein enzymes could provide efficient models to investigate the compositional dynamics of oligonucleotides.