Understanding the emergence of life from (primitive) abiotic components has arguably been one of the deepest and yet one of the most elusive scientific questions. Notwithstanding the lack of a clear definition for a living system, it is widely argued that heredity (involving self-reproduction) along with compartmentalization and metabolism are key features that contrast living systems from their non-living counterparts. A minimal living system may be viewed as “a self-sustaining chemical system capable of Darwinian evolution”. It has been proposed that autocatalytic sets of chemical reactions (ACSs) could serve as a mechanism to establish chemical compositional identity, heritable self-reproduction, and evolution in a minimal chemical system. Following years of theoretical work, autocatalytic chemical systems have been constructed experimentally using a wide variety of substrates, and most studies, thus far, have focused on the demonstration of chemical self-reproduction under specific conditions. While several recent experimental studies have raised the possibility of carrying out some aspects of experimental evolution using autocatalytic reaction networks, there remain many open challenges. In this review, we start by evaluating theoretical studies of ACSs specifically with a view to establish the conditions required for such chemical systems to exhibit self-reproduction and Darwinian evolution. Then, we follow with an extensive overview of experimental ACS systems and use the theoretically established conditions to critically evaluate these empirical systems for their potential to exhibit Darwinian evolution. We identify various technical and conceptual challenges limiting experimental progress and, finally, conclude with some remarks about open questions.

A biological system consists of a variety of polymers that are synthesized from monomers, by catalysis that exists only for some long polymers. It is important to elucidate the emergence and sustenance of such autocatalytic polymerization. We analyze here the stochastic polymerization reaction dynamics, to investigate the transition time from a state with almost no catalysts to a state with sufficient catalysts. We found an optimal volume that minimizes this transition time, which agrees with the inverse of the catalyst concentration at the unstable fixed point that separates the two states, as is theoretically explained. Relevance to the origin of life is also discussed.All life systems known so far consist of a wide variety of polymers that catalyze each other and are replicated through catalytic reactions. In cells, for instance, ribosomes whose main component are RNAs that synthesize a variety of protein species, such as polymerases, that catalyze RNA replication [1]. When considering the origins of life, it is therefore necessary to understand the emergence of a primordial polymer system that allows for self-replicating catalytic reactions, in which resource monomers such as amino acids or nucleotides, which are the building blocks of polymers, are supplied [2,3]. It is also important to understand the timescale of the synthesis of catalytic polymers by polymerizing reactions of the monomers.In this scenario, a polymer has to be long enough to function as a catalyst. In general, without catalysts, a chemical reaction to synthesize such a long polymer is extremely slow, while polymers, even if they are synthesized, are constantly degraded or diffused out. The synthesis can overcome possible degradation or diffusion only under catalysts (enzyme for protein; ribozyme for RNA) that accelerate the reaction by 10 7 ∼ 10 19 [4]. To sustain such a catalytically active state, a certain amount of catalysts is needed, which in turn is only synthesized from catalysts. Hence, the reaction system with autocatalytic polymers is expected to exhibit bi-stability between the inactive state with almost no catalysts and the active state with abundant catalysts that reproduce themselves. In fact, the importance of the transition from the inactive to active state for the emergence of a primitive replicating system has already been pointed out in the seminal work by Dyson [5], while catalytic reaction networks have also been extensively studied [6][7][8][9][10][11]. Here, we study this problem by considering a simple autocatalytic polymerization process, with an aim to obtain the time required for the transition from the inactive to active states.The existence of bistable states and the transition to a catalytically active state has been discussed recently [12,13]. In these studies, the rate equation of the concentrations of the monomers and polymers were often adopted. However, when considering the emergence of catalytic polymers, the number of molecules with negligible fluctuations may not be so large. These fluctuations enable...

We demonstrate that a recombinase ribozyme achieves multiple functions in the same reaction network: self-reproduction, iterative elongation and circularization of other RNAs, leading to synthesis of diverse products predicted by...