Emergence of ATP- and GTP-Binding Aptamers from Single RNA Sequences by Error-Prone Replication and Selection

The spontaneous emergence of function from diverse RNA sequence pools is widely considered an important transition in the origin of life. Here we show that diverse sequence pools are not a prerequisite for the emergence of function. Starting five independent selection experiments each from a single RNA seed sequence - comprising a central homopolymeric poly-A (or poly-U) segment flanked by different conserved primer binding sites - we observe transformation (continuous drift) of the seeds into low diversity sequence pools by mutation, truncation and recombination without ever reaching that of a random pool even after 24 rounds. Upon continuous error prone replication and selection for ATP binding we isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. Our results have implications for early RNA evolution in the light of the high mutation rates associated with both non-enzymatic and enzymatic prebiotic RNA replication.

Automated summary

We demonstrate that diverse sequence pools are not necessary for the emergence of function. By starting with a single RNA seed sequence and subjecting it to mutation, truncation, and recombination, we observe the transformation of the seed into a low diversity sequence pool. Through continuous error-prone replication and selection, we are able to isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. These findings have significant implications for the understanding of early RNA evolution.