Selection of prebiotic oligonucleotides by cyclic phase separation

TL;DR

This paper presents a novel prebiotic selection mechanism where cyclic phase separation and sedimentation enrich specific oligonucleotide sequences, potentially aiding the emergence of functional self-replicating molecules on early Earth.

Contribution

It introduces a sequence-specific selection process based on phase separation cycles, supported by theory and DNA experiments, highlighting a plausible prebiotic molecular screening method.

Findings

Sequence-specific enrichment of DNA in dense phase.

Enrichment favors complementary, base-paired sequences.

Weak initial biases can be amplified through cycles.

Abstract

The emergence of functional oligonucleotides on early Earth required a molecular selection mechanism to screen for specific sequences with prebiotic functions. Cyclic processes such as daily temperature oscillations were ubiquitous in this environment and could trigger oligonucleotide phase separation. Here, we propose sequence selection based on phase separation cycles realized through sedimentation in a system subjected to the feeding of oligonucleotides. Using theory and experiments with DNA, we show sequence-specific enrichment in the sedimented dense phase, in particular of short 22-mer DNA sequences. The underlying mechanism selects for complementarity, as it enriches sequences that tightly interact in the condensed phase through base-pairing. Our mechanism also enables initially weakly biased pools to enhance their sequence bias or to replace the most abundant sequences as the cycles progress. Our findings provide an example of a selection mechanism that may have eased screening for the first auto-catalytic self-replicating oligonucleotides.