  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.
