Synthesis and Characterization of Informational Molecules of Early Earth

Abstract

All processes in extant biology are facilitated by information encoded in polymers. Therefore, the origin of informational molecules had to be a crucial process in the origin of life on Earth. An important molecule in this context is RNA and the RNA World has been hypothesized as a pivotal step in the transition from chemistry to biology. However, the RNA molecule is comprised of intra-molecular bonds which are prone to hydrolysis under the harsh conditions that are thought to have been prevalent on the early Earth [1]. Furthermore, the formation of nucleotides with extant bases and their subsequent polymerization both have been problematic. Certain environmental niches, such as volcanic geo-thermal pools, may allow the formation of RNA-like polymers. Dehydration-rehydration (DH-RH) conditions which mimic diurnal or seasonal cycles result in formation of kinetic traps which may facilitate uphill polymerization reactions [2]. However, the low pH and high temperature conditions that are required for such polymerization also result in the cleavage of the N-glycosidic bond, thereby producing oligomers with abasic sites [3]. In the initial part of the present study, we set out to characterize the effect of prolonged DH-RH cycling on the stability of resultant molecules and also looked at how it might affect the product distribution. Our observations indicate lower fitness for modern nucleobases under prebiotically relevant conditions. These results are also supported by older experiments wherein formation of nucleosides with extant bases itself was shown to be difficult. Alternate bases, on the other hand, have resulted in formation of nucleosides with higher yields suggesting a viable and prebiotically relevant solution to the longstanding “nucleoside problem” [4]. We also recently demonstrated the synthesis of a plausible pre-RNA World nucleotide using ribose 5'-monophosphate (rMP) and barbituric acid (BA) as the base analog, under dry-heating conditions [5]. This result was simultaneously also demonstrated by the Hud group thus strengthening the more recently posited pre-RNA World hypothesis [6]. Furthermore, polymerization of the resultant monomer i.e. the BA-nucleotide was also observed when we carried out DH-RH cycles at low pH and high temperature. The resulting RNA-like oligomers seem to have intact bases unlike the reactions that were carried out using canonical nucleotides. Additionally, incorporation of BA onto preformed sugar-phosphate backbones was also observed when rMP oligomers were heated with BA. These results provide important preliminary evidence that alternate bases could have gotten incorporated into early polymers that may have predated the molecules of an RNA-World. Moreover, it also highlights the possibility that the prebiotic soup, which would have contained several types of heterocycles, might have facilitated simultaneous sampling of other potential pre-RNA World heterocycles as well. We will discuss the selective advantage that such primitive informational polymers could have had under pertinent selection pressures. Importantly, how these kinds of processes may have implications for shaping the prebiotic landscape that allowed for the emergence of primitive informational polymers of the pre-RNA World(s), prior to the emergence of a putative RNA World.

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