Sequence Selection and Replication in Phase-Separated Systems

Abstract

The emergence of highly selective catalytic sequences was a crucial step towards the origin of life. Templated ligation of RNA has been proposed as a pre-biotic mechanism to achieve self-replicating sequences without complex cellular machinery. A question remained as to how sufficiently long and abundant sequences can emerge from short nucleotides in a prebiotic sequence pool. Recently it was shown that sequence selection arises in oligomers subject to polymerisation and non-equilibrium fragmentation at dilute and non-dilute conditions. However, it is still elusive as to how sequence interactions under non-dilute conditions can give rise to a replication mechanism. In this work, we introduce a pathway for the oligomers to undergo templated ligation at non- dilute conditions in a phase-separated setting. We find that phase-separation enhances the selection pressure of this mechanism, resulting in a distribution dominated by highly structured sequences, thereby reducing the entropy of the product sequence space. Our results highlight that out-of- equilibrium condensed phases could provide versatile hubs for Darwinian-like evolution towards functional sequences, relevant both for molecular origins of life as well as de-novo life.