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. 2024 Mar 26:12:RP91397.
doi: 10.7554/eLife.91397.

Emergence of catalytic function in prebiotic information-coding polymers

Alexei V Tkachenko  1 , Sergei Maslov  2   3   4
Affiliations

Emergence of catalytic function in prebiotic information-coding polymers

Alexei V Tkachenko et al. Elife. .

Abstract

Life as we know it relies on the interplay between catalytic activity and information processing carried out by biological polymers. Here we present a plausible pathway by which a pool of prebiotic information-coding oligomers could acquire an early catalytic function, namely sequence-specific cleavage activity. Starting with a system capable of non-enzymatic templated replication, we demonstrate that even non-catalyzed spontaneous cleavage would promote proliferation by generating short fragments that act as primers. Furthermore, we show that catalytic cleavage function can naturally emerge and proliferate in this system. Specifically, a cooperative catalytic network with four subpopulations of oligomers is selected by the evolution in competition with chains lacking catalytic activity. The cooperative system emerges through the functional differentiation of oligomers into catalysts and their substrates. The model is inspired by the structure of the hammerhead RNA enzyme as well as other DNA- and RNA-based enzymes with cleavage activity that readily emerge through natural or artificial selection. We identify the conditions necessary for the emergence of the cooperative catalytic network. In particular, we show that it requires the catalytic rate enhancement over the spontaneous cleavage rate to be at least 102-103, a factor consistent with the existing experiments. The evolutionary pressure leads to a further increase in catalytic efficiency. The presented mechanism provides an escape route from a relatively simple pairwise replication of oligomers toward a more complex behavior involving catalytic function. This provides a bridge between the information-first origin of life scenarios and the paradigm of autocatalytic sets and hypercycles, albeit based on cleavage rather than synthesis of reactants.

Keywords: cleavage; evolutionary biology; heteropolymers; none; orgin of life; ribozyme; templated replication.

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Conflict of interest statement

AT, SM No competing interests declared

Figures

Figure 1.
Figure 1.. Illustration of two model variants.
(A) Random cleavage model. A random break in a chain of type c generates two primer fragments, which are elongated to give rise to two chains of type c. Elongation requires a complementary template of type c¯. (B) An example of catalyzed cleavage given by hammerhead ribozyme (Pley et al., 1994). Note that the right cleavage fragment is perfectly complementary to the blue sequence, while the left one contains an extra non-complementary base C. (C) Catalyzed cleavage model. A cleavage of the red chain a catalyzed by the blue chain b¯ gives rise to two primers aL (red) and aR (purple). Because of an extra non-complementary base (see B), the aL primer can only elongate to a, while the aR primer – to either a or b depending on its first hybridization partner. Similar processes involving complementary chains a¯ and b¯ (not shown) result in the replication of templates.
Figure 2.
Figure 2.. Dynamical phase portraits for different catalytic cleavage rates β.
(A) The phase portrait for a small catalytic cleavage rate β=6 has two non-cooperative steady-state solutions marked with red and blue stars corresponding to pure a/a¯ and pure b/b¯ subpopulations, respectively. These solutions are maintained by random rather than catalytic cleavage. (B) The phase portrait for intermediate catalytic cleavage rate β=10 in addition to two non-cooperative steady states marked with red and blue stars has a cooperative steady state marked with the green star in which all four subpopulations coexist. One can reach this state, for example, starting from the non-cooperative b/b¯ steady state (the blue star) and adding a relatively small subpopulation of a/a¯>2e−5 crossing the saddle point separating blue and green trajectories. (C) The phase portrait for a large catalytic cleavage rate β=18 again has only two non-cooperative cleavage steady states marked with red and blue stars. All three panels were obtained by numerically solving dynamical Equations 7–11 with random cleavage rate β0=0.015, elongation asymmetry factor λ=2, and dilution factor δ=1.
Figure 3.
Figure 3.. Properties of the cooperative state.
(A) The relationship between parameters of the cooperative state. mcoop∗/m∗ plotted vs. β for λ=2, δ=1 and increasing values of β0: 0.015 (green), 0.003 (purple), and 0.0045 (red). Lines are given by the parametric equation describing the state and derived in the SI Appendix (Equation S14), while open circles are obtained by direct numerical solution of dynamical equations (7–11). Monotonically increasing branches (solid lines) correspond to the stable cooperative fixed point, while the decreasing branches (dashed lines) – to the dynamically unstable saddle points separating different steady-state solutions in Figure 2B. (B) Phase diagram of the cooperative state. The shaded region marks the values of β/δ and β0/δ for which the cooperative solution exists. Green, purple, and red lines show the ranges of β for which the cooperative solution exists for the corresponding value of β0 shown in (A). Increasing the parameter β0 makes the range of β for which the cooperative solution exists progressively smaller until it altogether disappears above. β0/δ≈0.057.
Figure 4.
Figure 4.. The fitness landscape of our system.
(A) the three-dimensional plot and (B) the heatmap of the fitness m∗/mcoop∗ of the cooperative state in our system as a function of the catalytic cleavage rate enhancement β/β0 and elongation asymmetry λ. The co-evolution of λ and β would increase together. A typical evolutionary trajectory in which small changes in these parameters are independent of each other is shown as a dashed line.
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Update of

  • doi: 10.1101/2023.04.11.536473
  • doi: 10.7554/eLife.91397.1
  • doi: 10.7554/eLife.91397.2

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