Limited Sequence Diversity Within a Population Supports Prebiotic RNA Reproduction

The origins of life require the emergence of informational polymers capable of reproduction. In the RNA world on the primordial Earth, reproducible RNA molecules would have arisen from a mixture of compositionally biased, poorly available, short RNA sequences in prebiotic environments. However, it remains unclear what level of sequence diversity within a small subset of population is required to initiate RNA reproduction by prebiotic mechanisms. Here, using a simulation for template-directed recombination and ligation, we explore the effect of sequence diversity in a given population for the onset of RNA reproduction. We show that RNA reproduction is improbable in low and high diversity of finite populations; however, it could robustly occur in an intermediate sequence diversity. The intermediate range broadens toward higher diversity as population size increases. We also found that emergent reproducible RNAs likely form autocatalytic networks and collectively reproduce by catalyzing the formation of each other, allowing the expansion of information capacity. These results highlight the potential of abiotic RNAs, neither abundant nor diverse, to kick-start autocatalytic reproduction through spontaneous network formation

Limited Sequence Diversity Within a Population Supports Prebiotic RNA Reproduction

The origins of life require the emergence of informational polymers capable of reproduction. In the RNA world on the primordial Earth, reproducible RNA molecules would have arisen from a mixture of compositionally biased, poorly available, short RNA sequences in prebiotic environments. However, it remains unclear what level of sequence diversity within a small subset of population is required to initiate RNA reproduction by prebiotic mechanisms. Here, using a simulation for template-directed recombination and ligation, we explore the effect of sequence diversity in a given population for the onset of RNA reproduction. We show that RNA reproduction is improbable in low and high diversity of finite populations; however, it could robustly occur in an intermediate sequence diversity. The intermediate range broadens toward higher diversity as population size increases. We also found that emergent reproducible RNAs likely form autocatalytic networks and collectively reproduce by catalyzing the formation of each other, allowing the expansion of information capacity. These results highlight the potential of abiotic RNAs, neither abundant nor diverse, to kick-start autocatalytic reproduction through spontaneous network formation

Primitive Compartmentalization for the Sustainable Replication of Genetic Molecules

Sustainable replication and evolution of genetic molecules such as RNA are likely requisites for the emergence of life; however, these processes are easily affected by the appearance of parasitic molecules that replicate by relying on the function of other molecules, while not contributing to their replication. A possible mechanism to repress parasite amplification is compartmentalization that segregates parasitic molecules and limits their access to functional genetic molecules. Although extent cells encapsulate genomes within lipid-based membranes, more primitive materials or simple geological processes could have provided compartmentalization on early Earth. In this review, we summarize the current understanding of the types and roles of primitive compartmentalization regarding sustainable replication of genetic molecules, especially from the perspective of the prevention of parasite replication. In addition, we also describe the ability of several environments to selectively accumulate longer genetic molecules, which could also have helped select functional genetic molecules rather than fast-replicating short parasitic molecules

Spontaneous Advent of Genetic Diversity in RNA Populations Through Multiple Recombination Mechanisms

There are several plausible abiotic synthetic routes from prebiotic chemical materials to ribonucleotides and even short RNA oligomers. However, for refinement of the RNA World hypothesis to help explain the origins of life on the Earth, there needs to be a manner by which such oligomers can increase their length and expand their sequence diversity. Oligomers longer than at least 10-20 nucleotides would be needed for raw material for subsequent natural selection. Here, we explore spontaneous RNA-RNA recombination as a facile means by which such length and diversity enhancement could have been realized. Motivated by the discovery that RNA oligomers stored for long periods of time in the freezer expand their lengths, we systematically investigated RNA-RNA recombination processes. In addition to one known mechanism, we discovered at least three new mechanisms. In these, one RNA oligomer acts as a splint to catalyze the hybridization of two other oligomers and facilitates the attack of a 5\u27-OH, a 3\u27-OH, or a 2\u27-OH nucleophile of one oligomer onto a target atom of another. This leads to the displacement of one RNA fragment and the production of new recombinant oligomers. We show that this process can explain the spontaneous emergence of sequence complexity, both in vitro and in silico

Plausible pathway for a host-parasite molecular replication network to increase its complexity through Darwinian evolution

How the complexity of primitive self-replication molecules develops through Darwinian evolution remains a mystery with regards to the origin of life. Theoretical studies have proposed that coevolution with parasitic replicators increases network complexity by inducing inter-dependent replication. Particularly, Takeuchi and Hogeweg proposed a complexification process of replicator networks by successive appearance of a parasitic replicator followed by the addition of a new host replicator that is resistant to the parasitic replicator. However, the feasibility of such complexification with biologically relevant molecules is still unknown owing to the lack of an experimental model. Here, we investigated the plausible complexification pathway of host-parasite replicators using both an experimental host-parasite RNA replication system and a theoretical model based on the experimental system. We first analyzed the parameter space that allows for sustainable replication in various replication networks ranging from a single molecule to three-member networks using computer simulation. The analysis shows that the most plausible complexification pathway from a single host replicator is the addition of a parasitic replicator, followed by the addition of a new host replicator that is resistant to the parasite, consistent with the previous study by Takeuchi and Hogeweg. We also provide evidence that the pathway actually occurred in our previous evolutionary experiment. These results provide experimental evidence that a population of a single replicator spontaneously evolves into multi-replicator networks through coevolution with parasitic replicators. Author summary How primitive simple self-replication molecules develop their complexity through evolution is one of the largest mysteries in the origin of life. The largest obstacle in the development of complexity is parasitic replicators, which spontaneously appear and destroy inter-molecular cooperative networks, such as hypercycles, and simplify the replication system. However, Takeuchi and Hogeweg found that parasitic replicators could increase the complexity of replication network by working as a “niche” for multiple host replicators. This idea provides an attractive answer to the long-standing mystery, that is, how complexity of a molecular replication system develops, although experimental evidence is lacking. In the present study, we performed a theoretical analysis of an RNA replication system using computer simulation, together with experimental verification, to understand the reason for sustainable co-replication of multiple replicators. We also found that the most plausible route for complexity in the host–parasite replication network is the addition of the parasite first, followed by a new host that is resistant to the parasite. These results provide both theoretical and experimental evidence that parasitic replicators mediate the development of complexity in replication networks through Darwinian evolution

Emergence of linkage between cooperative RNA replicators encoding replication and metabolic enzymes through experimental evolution.

The integration of individually replicating genes into a primitive chromosome is a key evolutionary transition in the development of life, allowing the simultaneous inheritance of genes. However, how this transition occurred is unclear because the extended size of primitive chromosomes replicate slower than unlinked genes. Theoretical studies have suggested that a primitive chromosome can evolve in the presence of cell-like compartments, as the physical linkage prevents the stochastic loss of essential genes upon division, but experimental support for this is lacking. Here, we demonstrate the evolution of a chromosome-like RNA from two cooperative RNA replicators encoding replication and metabolic enzymes. Through their long-term replication in cell-like compartments, linked RNAs emerged with the two cooperative RNAs connected end-to-end. The linked RNAs had different mutation patterns than the two unlinked RNAs, suggesting that they were maintained as partially distinct lineages in the population. Our results provide experimental evidence supporting the plausibility of the evolution of a primitive chromosome from unlinked gene fragments, an important step in the emergence of complex biological systems

Relaxed Substrate Specificity in Qβ Replicase through Long-Term In Vitro Evolution

A change from RNA- to DNA-based genetic systems is hypothesized as a major transition in the evolution of early life forms. One of the possible requirements for this transition is a change in the substrate specificity of the replication enzyme. It is largely unknown how such changes would have occurred during early evolutionary history. In this study, we present evidence that an RNA replication enzyme that has evolved in the absence of deoxyribonucleotide triphosphates (dNTPs) relaxes its substrate specificity and incorporates labeled dNTPs. This result implies that ancient replication enzymes, which probably evolved in the absence of dNTPs, could have incorporated dNTPs to synthesize DNA soon after dNTPs became available. The transition from RNA to DNA, therefore, might have been easier than previously thought

Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats

Purpose: Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model. Methods: EIU was induced in Lewis rats via 200 mu g subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor alpha (TNF-alpha) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) kappa B antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples. Results: The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-alpha concentrations in aqueous humor (p<0.01). The numbers of NF kappa B-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05). Conclusions: Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NF kappa B and TNF-alpha. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful