Systems protobiology: origin of life in lipid catalytic networks

Abstract

Life is that which replicates and evolves, but there is no consensus on how life emerged. We advocate a systems protobiology view, whereby the first replicators were assemblies of spontaneously accreting, heterogeneous and mostly non-canonical amphiphiles. This view is substantiated by rigorous chemical kinetics simulations of the graded autocatalysis replication domain (GARD) model, based on the notion that the replication or reproduction of compositional information predated that of sequence information. GARD reveals the emergence of privileged non-equilibrium assemblies (composomes), which portray catalysis-based homeostatic (concentration-preserving) growth. Such a process, along with occasional assembly fission, embodies cell-like reproduction. GARD pre-RNA evolution is evidenced in the selection of different composomes within a sparse fitness landscape, in response to environmental chemical changes. These observations refute claims that GARD assemblies (or other mutually catalytic networks in the metabolism first scenario) cannot evolve. Composomes represent both a genotype and a selectable phenotype, anteceding present-day biology in which the two are mostly separated. Detailed GARD analyses show attractor-like transitions from random assemblies to self-organized composomes, with negative entropy change, thus establishing composomes as dissipative systems—hallmarks of life. We show a preliminary new version of our model, metabolic GARD (M-GARD), in which lipid covalent modifications are orchestrated by non-enzymatic lipid catalysts, themselves compositionally reproduced. M-GARD fills the gap of the lack of true metabolism in basic GARD, and is rewardingly supported by a published experimental instance of a lipid-based mutually catalytic network. Anticipating near-future far-reaching progress of molecular dynamics, M-GARD is slated to quantitatively depict elaborate protocells, with orchestrated reproduction of both lipid bilayer and lumenal content. Finally, a GARD analysis in a whole-planet context offers the potential for estimating the probability of life's emergence. The invigorated GARD scrutiny presented in this review enhances the validity of autocatalytic sets as a bona fide early evolution scenario and provides essential infrastructure for a paradigm shift towards a systems protobiology view of life's origin.

Survival of self-replicating molecules under transient compartmentalization with natural selection

“…Another important direction for future work would be to consider a large number of interacting chemical species, a situation frequently encountered in Statistical Physics [24]. In this case, we expect that the basic unit of description may no longer be that of single chemical species, but could become collective excitations of the composition, similar to quasi-species [25] or composomes [26]. A general theory of non-equilibrium chemical networks, constrained by conservation laws and symmetries has been recently put forward [27,28].…”

Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry

“…Indeed, it is known that biomolecules represent a minute fraction of the molecular diversity produced by prebiotic chemistry (as mentioned above) and this would tend to lower the probability that chemical bonds formed exclusively among biomolecules particularly in a one-pot prebiotic synthesis [3,24,28]. The possible importance of Life 2020, 10, 6 4 of 16 non-biomolecules in the OoL has been suggested previously as a sort of "chemical opportunism" [29]. According to this notion whatever molecules conferred the greatest selective advantage (via function, persistence, availability, etc.)…”

“…A notional example of such "chemical opportunism" is the emergent systemic autocatalysis proposed by [30]. The idea that the first autocatalytic chemical systems could have been composed of non-biomolecules has also been proposed by Lancet and coworkers [19,29]. More nuanced examples of primitive non-biomolecular systems, include those incorporating purely in vitro-produced polymers (themselves produced from biomolecular components such as amino acids) which do not participate in modern biology, have also been explored including self-assemblies of lipid-like peptides [31].…”

Programming Multistationarity in Chemical Replication Networks

“…We show numerically, and by simulating many cases, that this yields multistationarity or multistability (Figure e), i. e., multiple stable steady‐state solutions (see formal mathematical definitions by Joshi and Shiu), where the specific points of convergence depend on the efficiency of each replicator and the system's initial conditions. As shown in various numerical studies of replication networks, the current system also displays patterns of behavior that are difficult to predict without simulation. Furthermore, the simulations reveal fundamental trends and characteristics potentially useful for design of future experiments.…”