Heat-Flow-Driven Oligonucleotide Gelation Separates Single-Base Differences.

DNA phase transitions are often induced by the addition of condensation agents or by dry concentration. Herein, we show that the non-equilibrium setting of a moderate heat flow across a water-filled chamber separates and gelates DNA strands with single-base resolution. A dilute mix of DNA with two slightly different gel-forming sequences separates into sequence-pure hydrogels under constant physiological solvent conditions. A single base change in a 36 mer DNA inhibits gelation. Only sequences with the ability to form longer strands are concentrated, further elongated, and finally gelated by length-dependent thermal trapping. No condensation agents, such as multivalent ions, were added. Equilibrium aggregates from dry concentration did not show any sequence separation. RNA is expected to behave identically owing to its equal thermophoretic properties. The highly sequence-specific phase transition points towards new possibilities for non-equilibrium origins of life.