Heat flux across an open pore enables the continuous replication and selection of oligonucleotides towards increasing length

Journal name:
Nature Chemistry
Year published:
Published online


The replication of nucleic acids is central to the origin of life. On the early Earth, suitable non-equilibrium boundary conditions would have been required to surmount the effects of thermodynamic equilibrium such as the dilution and degradation of oligonucleotides. One particularly intractable experimental finding is that short genetic polymers replicate faster and outcompete longer ones, which leads to ever shorter sequences and the loss of genetic information. Here we show that a heat flux across an open pore in submerged rock concentrates replicating oligonucleotides from a constant feeding flow and selects for longer strands. Our experiments utilize the interplay of molecular thermophoresis and laminar convection, the latter driving strand separation and exponential replication. Strands of 75 nucleotides survive whereas strands half as long die out, which inverts the above dilemma of the survival of the shortest. The combined feeding, thermal cycling and positive length selection opens the door for a stable molecular evolution in the long-term microhabitat of heated porous rock.

At a glance


  1. Reduction of local entropy is key for living systems and can be caused by the flux of thermal energy.
    Figure 1: Reduction of local entropy is key for living systems and can be caused by the flux of thermal energy.

    a, Modern cells feed on chemical energy, which enables them to host, maintain and replicate information-coding polymers, processes necessary for Darwinian evolution. b, The flux of thermal energy across geological cracks near a heat source (the white smoker28 is adapted from an image courtesy of Deborah S. Kelley). c, (1) A thermal gradient across a millimetre-sized crack induces the accumulation of molecules by thermophoresis and convection. (2) A global throughflow imports nutrients into the open pore. (3) Exponential replication is facilitated by the local convection, which shuttles the molecules repetitively between warm and cold, and thus induces the cyclic denaturation of nucleotides. (4) The combination of influx, thermophoresis and convection selectively traps long molecules and flushes out short ones. The inflow speed determines the cut-off size of the resulting length selection. Mechanisms (1) to (4) are described in detail in this article.

  2. Accumulation of oligonucleotides.
    Figure 2: Accumulation of oligonucleotides.

    a, The temperature gradient drives oligonucleotides horizontally from warm to cold by thermophoresis and simultaneously triggers the vertical thermal convection of water. Its combination results in a length-dependent accumulation at the bottom of an elongated pore within minutes (see Supplementary Movie 2). b, The accumulation of dilute double-stranded oligonucleotides (100–1,000mer) at the bottom is monitored within a 100 µm thin and 2 mm high capillary via ​SYBR Green I fluorescence. c, The accumulation is dynamic: the nucleotides cycle between the warm and cold sides, visualized in white for a single 500mer of DNA.

  3. Heat-driven filter selecting for strand length.
    Figure 3: Heat-driven filter selecting for strand length.

    a, A steady upwards feeding flow is triggered by opening the asymmetrically heated pore. A ladder of dsDNA (20–200 bp, 20 bp steps) was injected into the trap. Subsequent flushing of the capillary with pure buffer at a single velocity (vs = 6 µm s–1) revealed the filter's thresholding characteristics—lengths ≤80 bp flow through the pore whereas longer strands are trapped. b, An asymmetric flow pattern is generated by the superposition of the upwards flow and the convection. Thermophoresis pushes the long strands into the downwards flow and traps them. Short strands are subjected to the overall upwards flow and leave the pore. The trapping is a function of the feeding flow speed. c, The velocity of the external flow vs tunes the fractionation of nucleic acids. As in the experiment before, a DNA ladder was initially introduced at a low flow velocity, which was then sequentially increased. The released DNA was measured using gel electrophoresis. d, The fraction of trapped DNA obtained from the electrophoresis gel constitutes a selection landscape of this thermal habitat in favour of long oligonucleotides. The velocity-dependent trapped fraction is described by a fluid dynamics model (see Methods). Error bars reflect the signal-to-noise ratio of the gel images (see Supplementary Fig. 11 for details).

  4. Selection of a replicating DNA population that occupies the thermal habitat.
    Figure 4: Selection of a replicating DNA population that occupies the thermal habitat.

    a, Strands are subjected to temperature oscillations by the combination of thermophoresis, convection, feeding flow and diffusion. Simulations of stochastic molecule traces show that strands of 75 bp cycle inside the system for 18 minutes on average. In comparison, 36mers, owing to their enhanced diffusion, show faster temperature cycles, but are flushed out of the system after five minutes. b, Taq DNA polymerase-assisted replication of 80mer dsDNA by convective temperature cycling. Quantitative ​SYBR Green I fluorescence measurements show an exponential replication with a doubling time of 102 seconds (see Supplementary Movie 4). c, An open pore (see Fig. 1c) was seeded with a binary population of nucleic acids. Quantitative gel electrophoresis revealed sustainable replication for only the long strand. Short strands became diluted and then extinct despite their faster replication. d, Relative concentrations of the two competing species inside the thermal habitat. The selection pressure of the thermal gradient altered the composition of the binary population with time (yellow diamonds) in good agreement with an analytical replication model. The absolute fitness values were 1.03 and 0.87 for long and short strands, respectively. Without the thermal gradient, the short oligonucleotides won over the long strands (blue circles), analogous to the Spiegelman experiment. Error bars reflect the signal-to-noise ratio of the gel images (see Supplementary Fig. 11 for details).


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Author information

  1. Present address: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany

    • Moritz Kreysing
  2. These authors contributed equally to this work

    • Moritz Kreysing,
    • Lorenz Keil &
    • Simon Lanzmich


  1. Systems Biophysics, Physics Department, Center for Nanoscience, Ludwig-Maximilians-Universität München, 80799 Munich, Germany

    • Moritz Kreysing,
    • Lorenz Keil,
    • Simon Lanzmich &
    • Dieter Braun


M.K., L.K. and S.L. contributed equally to this work and performed the experiments. M.K., L.K., S.L and D.B. conceived and designed the experiments, analysed the data and wrote the paper.

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