Selection–diversification interplay in oligonucleotide chemical evolution

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.

Caption of Graphical Abstract

The RNA world hypothesis posits that activated nucleotides oligomerized to short, random RNA sequences, which elongated to form longer-sequence pools, eventually giving rise to ribozymes. Throughout these chemical evolution processes, certain nucleotide compositions may have been selectively enriched or counterbalanced. An appropriate level of diversity could have enabled efficient sequence exploration and promoted the emergence of ribozymes.