Systems-chemistry approach to prebiotic evolution

The puzzle of the origin of life is grand. A major challenge is to understand the transition from a mixture of molecules into an entity with basic life faculties, such as a protocell, capable of self-replication and inheritance. Two major schools tackle this problem: the genetic, or replicator-first approach, and the metabolism-first approach. The replicator-first approach focuses on a single self-perpetuating informational biopolymer, e.g., RNA, as the first step, and it is thus often referred to as the “RNA world”. In contrast, the metabolism-first approach focuses on a network of chemical reactions among simpler chemical components that became endowed with some reproductive characteristics as the first step that led to a protocell. The lipid world scenario, largely initiated by our laboratory, delineates a specific example of metabolism first. It suggests that spontaneously forming assemblies of relatively simple molecules, such as mutually interacting lipids, that resemble primitive metabolism, are capable of storing and transmitting information similar to sequence-based polymeric RNA, except that in this case it is compositional information that is at work. This thesis is about further exploration of the lipid world scenario, showing in more detail how a relatively simple chemical system can acquire features such as selection and evolution. This was accomplished by studying dynamical aspects of the graded autocatalysis replication domain (GARD) computer-simulation lipid world model, previously developed at our laboratory. GARD simulates the homeostatic growth of a compositional amphiphile assembly by reversible accretion from a buffered heterogeneous external pool. This process is governed by a network of mutually catalytic reactions, and exhibits quasi-stationary compositional states termed compotype, that may be regarded as GARD species. I have demonstrated that that such GARD species exhibit positive as well as negative selection, an important prerequisite of a minimally living system. I further showed that when the catalytic network becomes dominated by mutual catalysis, as opposed to self-catalysis, selection is enhanced. When studying the dynamics of large populations of GARD assemblies under constant population conditions, I rewardingly found that they exhibit dynamics similar to natural ecosystem populations, e.g. similes of competition or predator-prey dynamics. I was able to establish relationships between a compotype’s internal molecular parameters (e.g. its molecular diversity) and population ecology behavior. In a separate vein, I have developed a new approach towards observing open-ended evolution, which enables asking whether there is an optimal level of open endedness in prebiotic evolution. Finally, I was able to show clear similarities between GARD compotypes and quasispecies in the Eigen-Schuster model for evolution, further underlining GARD’s capacity as an alternative to RNA World. Taken together, these results uncover quantitative aspects of the GARD model which in turn contribute towards our understanding of the origin of life via the lipid world scenario

Spontaneous chiral symmetry breaking in early molecular networks

Background: An important facet of early biological evolution is the selection of chiral enantiomers for molecules such as amino acids and sugars. The origin of this symmetry breaking is a long-standing question in molecular evolution. Previous models addressing this question include particular kinetic properties such as autocatalysis or negative cross catalysis. Results: We propose here a more general kinetic formalism for early enantioselection, based on our previously described Graded Autocatalysis Replication Domain (GARD) model for prebiotic evolution in molecular assemblies. This model is adapted here to the case of chiral molecules by applying symmetry constraints to mutual molecular recognition within the assembly. The ensuing dynamics shows spontaneous chiral symmetry breaking, with transitions towards stationary compositional states (composomes) enriched with one of the two enantiomers for some of the constituent molecule types. Furthermore, one or the other of the two antipodal compositional states of the assembly also shows time-dependent selection. Conclusion: It follows that chiral selection may be an emergent consequence of early catalytic molecular networks rather than a prerequisite for the initiation of primeval life processes. Elaborations of this model could help explain the prevalent chiral homogeneity in present-day living cells. Reviewers: This article was reviewed by Boris Rubinstein (nominated by Arcady Mushegian), Arcady Mushegian, Meir Lahav (nominated by Yitzhak Pilpel) and Sergei Maslov

Automated device for continuous stirring while sampling in liquid chromatography systems

Ultra-performance liquid chromatography is a common analysis tool, and stirring is common in many laboratory setups. Here we show a device which enables continuous stirring of samples whilst inside an ultra-performance liquid chromatography system. Utilizing standard magnetic stirring bars that fit standard vials, the device allows for the automation of experimental setups that require stirring. The device is designed such that it can replace the standard sample holder and fits in its place, while being battery operated. The use of three-dimensional (3D) printing and commercially available parts enables low-effort and low-cost device production, as well as easy modifications. Testing the device was performed by video analysis and by following the kinetics of a dynamic combinatorial library that is known to be exquisitely sensitive to agitation, as a result of involving a fiber growth-breakage mechanism. Design files and schematics are provided

Competition dynamics in a chemical system of self-replicating macrocycles

Central to the origin of life is the question how a chemical system transitioned from interacting molecules to an entity with the capacity for self-replication, diversification and adaptive evolution. Here, we study a chemical system that is comprised of macrocycles that have been shown to spontaneously give rise to self-replicating entities. By combining experimental and theoretical approaches, we strive to understand the evolutionary potential of this system. In particular, we apply eco-evolutionary reasoning to investigate whether and when this system of chemical replicators can diversify. Here, we report first results of a simplified stochastic chemical reaction model that is parameterized on the basis of experimental data. The model considers the competition of two replicators that do not interact directly but need similar building blocks for their growth and reproduction. Interestingly, the replicator that emerges first is being overtaken by the later one. By means of stochastic simulations, we will explore how the competitive ability of a replicator is determined by its chemical characteristics, and under which conditions replicators can coexist. The results will subsequently inform the design of future experiments

Out-of-equilibrium self-replication allows selection for dynamic kinetic stability in a system of competing replicators

Among the key characteristics of living systems are their ability to self-replicate and the fact that they exist in an open system away from equilibrium. Herein, we show how the outcome of the competition between two self-replicators, differing in size and building block composition, is different depending on whether the experiments are conducted in a closed vial or in an open and out-of-equilibrium replication-destruction regime. In the closed system, the slower replicator eventually prevails over the faster competitor. In a replication-destruction regime, implemented through a flow system, the outcome of the competition is reversed and the faster replicator dominates. The interpretation of the experimental observations is supported by a mass-action-kinetics model. These results represent one of the few experimental manifestations of selection among competing self-replicators based on dynamic kinetic stability and pave the way towards Darwinian evolution of abiotic systems

All-photochemical rotation of molecular motors with a phosphorus stereoelement

Unidirectional molecular rotation based on alternating photochemical and thermal isomerizations of overcrowded alkenes is well established, but rotary cycles based purely on photochemical isomerizations are rare. Herein we report three new second-generation molecular motors featuring a phosphorus center in the lower half, which engenders a unique element of axial chirality. These motors exhibit unusual behavior, in that all four diastereomeric states can interconvert solely photochemically. Kinetic analysis and modeling reveal that the behavior of the new motors is consistent with all-photochemical unidirectional rotation. Furthermore, X-ray crystal structures of all four diastereomeric states of two of these new motors were obtained, which constitute the first achievements of crystallographic characterization of the full 360° rotational cycle of overcrowded-alkene-based molecular motors. Finally, the axial phosphorus stereoelement in the phosphine motor can be thermally inverted, and this epimerization enables a “shortcut” of the traditional rotational cycle of these compounds