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Journal of Cosmology, 2010, Vol 10, 3381-3387. JournalofCosmology.com, August, 2010 Ernesto Di Mauro, Ph.D., Istituto Pasteur Fondazione Cenci Bolognetti c/o Dipartimento di Genetica e Biologia Molecolare, Università di Roma "Sapienza", Piazzale Aldo Moro, 5, 00185, Roma, Italy.
Key Words: prebiotic chemistry, formamide, chemical information, genetic polymers, origin of life.
1. LIFE AS AN ENSEMBLE OF EMERGENT PROPERTIES Definition of life is an open problem. The largely accepted wording: "Life is a self sustained chemical system capable of undergoing Darwinian evolution" (Joyce, 1994) attains a solid operative sense but it is more the description of a process than a formal definition of a system. The Darwinian notation entails variability. Up to which point is it allowed to base a definition on attributions that are only potential but are not yet actually embodied? Nevertheless, the fact remains that living entities are an ensemble of concerted chemical reactions, selected during the progression of time and integrated with pre-existing ones. This consideration frames life in the domain of processes, and processes may be characterized by emergent properties. According to an accepted, and acceptable, definition (Oxford Dictionary of Science, 2008) emergence is the key concept in complexity theory in which features of a system occur as a result of the collective behaviour of the system. If life is consequence of emergence, the emergent properties of living systems are the properties that were not present before the system reached that given level of complexity allowing it to fit into the accepted operative definition reported above. Hence, the emergent properties relevant for the definition are the characterizing properties of the living systems, those absent in the non-living. Condensing these considerations into an aphorism: emergent properties exist in what constitutes life which account for its coming into being. In this reasoning, the concept life becomes less elusive and can be defined by default: life is what has an in and an out, non-life is what does not have it. Life is what has a self distinct from a non-self, nonlife is what does not have it. Life is what reproduces itself, non-life is what does not. And, at the limit, life on planet Earth is the process in which emerge ribosomes, aminoacyltransferases, RNA polymerases, and all the other complexities that do not emerge in non-life. What about elsewhere? The vague problem of "what is life" becomes experimentally manoeuvrable: which are the first properties emerging from the intrinsic attributes of the chemically reactive system(s) laying at the root of what we describe as living? My operative suggestion is to start from the simple concept formalized by Steve Stenger: something came from nothing because was more stable than nothing (Stenger, 2006). Does a chemical frame exist in which we can follow from its very beginning the emergence of the special type of complexity obeying Darwinian rules that we dub life? Is this a really unitary and single-rooted chemical frame or is it the convergence of multiple independent flows of information-bearing molecules? Do other niches outside planet Earth exist in which such eventually identified fertile chemical frame can be traced? In this quest one should not to be a priori limited by preconceptions, biased by what we refer to as life based on our terrean experience. Anyhow, a terro-centric point of view is what we have to start with, keeping in mind its parochial limitations. We have difficulty in even formulating a rigorous definition of life, and certainly we do not know how it started. Hence, the approach to the search for the unique chemical frame into which the first reactions lighted up and started accumulating and evolving chemical information, can only be confronted, operationally, with a top-down approach. Starting from what is our experience of the biological domains, but ready to widen it. 2. A PLAUSIBLE UNITARY FRAME Living entities as-we-know-them are made of a genotype and of a phenotype, functionally integrated. For the sake of simplicity, we refer here to genotype as to the molecular structure able to conserve, express, replicate and evolve itself affording, in so doing, a number of programmed ancillary products. These facilitate (and in most cases plainly allow) its transmission beyond thermodynamically imposed limits. Not least, the genotype is not abstract information, itself being a phenotypically defined macromolecular structure. The genotypes we know are made of RNA and DNA. Exotic alternatives as PNA, TNA and others (see below) have great heuristic and pharmacological interest and are in many cases structurally elegant. However, they have not shown their worth in the prebiotic daybreak on planet Earth. In the absence of compelling arguments it is possibly safer, while searching for the ur-chemical frame, to maintain a conservative Occam-wise top-down approach: starting from RNA we might find that its precursors were, on this planet, energetically unspoiled plain ribonucleotides. RNA is considered as the possible shrine of the properties that kick-started evolution, DNA being the largely less reactive, thus more stable, depository of information. The "RNA world" hypothesis (Gilbert, 1986) admittedly deems DNA as a late-comer cellular invention. DNA needs for its synthesis and maintenance a complex endowment of enzymes, a protective chromatin mostly made of precisely located histones proteins (Travers et al. 2010) and a confined environment. The auto-catalytic properties of RNA (Chech, 1987 and references therein; Fedor & Williamson, 2005) and its ability to polymerize spontaneously generating itself from 3',5' cyclic nucleotides (Costanzo et al. 2009) hint to its function as pre-genetic material. Both RNA and DNA are made of the repetition of three components. A nucleic base bound to a sugar moiety connected to its nearest neighbours by phosphodiester bridges. A large number of alternatives are possible and were described. The alternatives pertain to each of the three components. Derivatives of the five canonical adenine (A), guanine (G), cytosine (C), uracil (U) or thymine (T) are present in extant nucleic acids, and a large number of other heterocyclic compounds were described (Benner and Hutter, 2002; Bean et al. 2007; references therein) as possible components of nucleic acids or of nucleic acids-like macromolecules. Different sugar moieties were studied in their ability to form nucleic skeletons (Kozlov et al. 1999; Schöning et al. 2000; Bean et al. 2006; references therein) and the connecting phosphatebased bridge was substituted by bridges connecting numerous different alternatives, from sulphonic to peptide-like groups (Egholm et al. 1992). The advantages of phosphate as linking group were discussed (Westheimer, 1987). Thus, nucleic acids may come in different forms, allowing the conclusion that what we know on planet Earth (A, G, C, U or T as heterocyclic bases; D-ribose or its deoxy-derivative as sugars; and phosphate as connecting bridge) is more related to the environment in which their functions evolved rather than to the chemical impossibility of alternatives. The question may thus be formulated: which other environments can be conceived and, ideally, do actually exist, allowing the formation of the precursors of self-replicating informational macromolecules and their condensation into polymers? 3. HCN/FORMAMIDE CHEMISTRY HCN is considered to be the precursor molecule of nucleic bases. The pioneering finding by Orò, who reported in the 1960s the synthesis of adenine from HCN (Orò and Kimball, 1960; Orò, 1961; Orò and Kimball, 1961) was followed by decades of thorough investigation of HCN chemistry [as reviewed in (Orgel, 2004) and (Delaye & Lazcano, 2005)]. More recently, the synthesis from formamide NH2COH (Saladino et al. 2005, 2007, 2009; Ciciriello et al. 2009) of a large variety of nucleic bases (including adenine, cytosine, uracil and thymine), of some of their precursors and of their degradation products was reported. Formamide affords its products simply by heating between 100 and 160°C in the presence of one or more of a large class of prebiotically available minerals: silica, alumina, zeolites, CaCO3, TiO2, common clays, kaolin, montmorillonites, olivines, phosphate minerals (reviewed in Saladino et al. 2005, 2007), sulphur and iron minerals (Saladino et al. 2008), zirconium-based (Saladino et al. 2010) and boron-based (unpublished) minerals. The fact that formamide yields nucleic bases when stimulated by all sorts of different catalysts indicates that this non-fastidious productive pathway is an intrinsic property of formamide itself. Guanine, missing from the panel of compounds obtained in heat presumably because of its instability, can be obtained from formamide by UV irradiation (Barks et al. 2010) at lower temperatures. The production in the same chemical frame of acyclonucleotides (Saladino et al. 2003), the abiotic phosphorylation of nucleosides to yield cyclic nucleotides (Costanzo et al. 2007), their nonenzymatic polymerization to yield long RNA chains (Costanzo et al. 2009), and the non-enzymatic terminal ligation of oligomers (Pino et al. 2008; Costanzo et al. 2009) show that the whole series of events leading from a one-carbon atom precursor (NH2COH) to RNA polymers may be accomplished within a single chemical frame. The synthesis of nucleosides in possibly prebiotic conditions in different chemical frames was also reported (Bean et al. 2007; Powner et al. 2009). The facts that formamide can be promptly obtained by reaction of HCN with H2O, and that it is liquid between 4 and 210°C with limited azeotropic effects, point to its potential relevance in different abiotic but life-oriented scenarios, possibly not limited to planet Earth. The abiotic origin of the first RNA polymers has been the focus of several proposals (Weimann et al.1968; Joyce et al. 1984a,b; Sawai et al. 1989; Eschenmoser 1999; Hud and Anet, 2000; Benner, 2004; Anastasi et al. 2007; Rajamani et al. 2008) entailing different physicalchemical scenarios, often suggesting distinct mechanisms to solve the problem of the presumably highly dilute concentration of the initial reactants. The simple nonequilibrium environment of a temperature gradient, compatible with conditions present in pores in hydrothermal rocks, suggests the physical set-up for efficient and prebiotically plausible concentration and replication mechanisms (Baaske et al. 2007; Mast and Braun 2010). 4. STABILITY-DRIVEN EMERGENCE Once formed, polymers can evolve only if the physical-chemical conditions of their environment and their intrinsic chemical properties allow them to survive in polymeric form. It was reported that the weak point of RNA (its 3' phosphoester bond) is more stable when embedded in a ribopolymer than when present in the monomer (Saladino et al. 2006). This observation accounts on one hand for the otherwise not easily understandable subsistence of polymeric information, on the other provides a logics for the identification of pro-life environments. The Stenger's aphorism mentioned above hints to the fact that the progression from disorder to order equals the progression from non-life to life. The progression towards stability goes from hydrogen to evolved atoms and from the combinations of the most frequent ones (carbon, nitrogen, oxygen) to their most abundant organic (HCN) and inorganic (H2O) combinations (www.astrochemistry.net). HCN and H2O combine to yield formamide H2NCOH, and we have mentioned how it is at least conceivable that by successive runs of condensation nucleic bases and their evolved nucleosidic and nucleotidic forms can be obtained. At this point the definition of life becomes a matter of description of which properties emerge from the intrinsic combinatorial potential of the spontaneously generated and Stenger-wise accumulated chemical information. Where thermodynamic niches exist in which formation, accumulation, activation and polymerization of chemical information is allowed, there life can start its Darwinian process towards complexity. Given that the chemistry of H, C, N, O and P is the same in the whole Universe, and that their combinations are expected to follow the same principles everywhere, the emerging properties are not expected to be basically different, here or out there. The differences of the life that will be found elsewhere will just reflect the differences imposed on its history by Darwinism at cosmological scale.
Acknowledgements: This work was jointly supported by NSF and the NASA Astrobiology Program, under the NSF Center for Chemical Evolution, CHE-1004570, by Italian Space Agency "MoMa project" and by ASI-INAF n. I/015/07/0 "Esplorazione del Sistema Solare".
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