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Theory for sequence selection via phase separation and oligomerization.

Ivar S Haugerud1, Giacomo Bartolucci1,2, Dieter Braun3

  • 1Faculty of Mathematics, Institute of Physics, Natural Sciences, and Engineering, University of Augsburg, Augsburg 86159, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|January 30, 2026
PubMed
Summary
This summary is machine-generated.

Condensed phases can drive the selection of specific DNA sequences through phase separation, influencing the origin of life. This process enriches functional sequences by creating nonequilibrium selection pressures.

Keywords:
nonequilibrium thermodynamicsoligomerizationorigins of lifephase separationsequence selection

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Area of Science:

  • Biochemistry
  • Chemical Thermodynamics
  • Origin of Life Studies

Background:

  • Non-equilibrium selection pressures are theorized to form functional oligonucleotides.
  • Phase separation is known to direct chemical processes, but its role in sequence selection is unexplored.

Purpose of the Study:

  • To investigate if condensed phases, specifically through phase separation, can act as a mechanism for sequence selection.
  • To understand how phase separation influences the formation and enrichment of specific oligonucleotide sequences.

Main Methods:

  • Utilized non-equilibrium thermodynamics to model reversible oligomerization of monomers under conditions favoring phase separation.
  • Analyzed sequence formation, phase separation dynamics, and fragmentation effects on sequence enrichment.

Main Results:

  • Sequence formation can trigger phase separation, leading to enrichment of certain sequences and depletion of others.
  • Phase separation creates a selection pressure under non-equilibrium conditions maintained by fragmentation.
  • Fragmentation rate influences selection: slow fragmentation favors alternating sequences, while fast fragmentation favors longer repeating motifs.

Conclusions:

  • Out-of-equilibrium condensed phases offer a selection mechanism for functional sequences.
  • Phase separation in condensed phases is a potential hub for the evolution of life's molecular origins.