Converting raw energy into biological energy

Orgel writes:Molecules that stay together evolve together.

The RNA World model for prebiotic evolution posits the selection of catalytic/template RNAs from random populations ... This low probability (of random interactions) could be overcome if the molecules capable of productive recombination were redundant, with many nonhomologous but functionally equivalent RNAs being present in a random population ... Parallel SELEX experiments showed that at least one in 106 random 20-mers binds to the P5.1 stem-loop of Bacillus subtilis RNase P RNA with affinities equal to that of its naturally occurring partner. This high frequency predicts that a single RNA in an RNA World would encounter multiple interacting RNAs within its lifetime, supporting recombination as a plausible mechanism for prebiotic RNA evolution. The large number of equivalent species implies that the selection of any single interacting species in the RNA World would be a contingent event, i.e., one resulting from historical accident.

Orgel writes:The inevitable conclusion of this survey of nucleotide synthesis is that there is at present no convincing, prebiotic total synthesis of any of the nucleotides.

Prebiotic chemistry experiments search to explain the origins and properties of chemical structures and reactions which may have been involved in the life emergence (for recent reviews see Eschenmoser and Loewenthal, 1992; Sutherland and Whitfield, 1997; Maurel and Décout, 1999). Small molecules present in the primitive Earth atmosphere such as water, carbon monoxide, sulfur dioxide, methane, dinitrogen (but not dioxygen) could react to lead to the elementary building blocks, ammonia, hydrogen cyanide, formaldehyde, acetonitrile, acrylonitrile, cyanogen and cyanoacetylene. Cosmic rays, ionizing radiations, electric discharges and radioactive process induced ion-molecule and radical reactions which led to these building blocks. From these molecules, formation of amino acids ( Miller and Miller; Joshi and Pathak, 1975; Kobayashi et al., 1998) and nucleic acid bases ( Or and Or; Or and Kimball, 1961; Ferris and Orgel, 1966; Robertson and Miller, 1995; Miyakawa et al., 1999) such as adenine 1 (Fig. 1, C5H5N5: pentamer of hydrogen cyanide) under prebiotic conditions could be explained. Many prebiotic molecules could already have been present in comets such as adenine detected into comet Halley dust. Or suggested that comets might already have brought to the Earth biochemical precursors necessary for emergence of life (Or, 1961; Or et al., 1992). Delsemme emphasized more and more evidences support that an intense bombardment of comets has brought to the Earth all the carbon compounds present in organic molecules used by life ( Delsemme and Delsemme 2000).

In the search of chemical prebiotic routes which could lead from nucleic acid bases to building blocks capable of polymerizing to form nucleic acids strands, we are investigating reactions of adenine with different aldehydes under presumably prebiotic conditions. Such reactions could have led to nucleoside and nucleoside-like building blocks endowed with catalytic properties necessary for life. Previously, Fel'dman (1962) reported slow reactions of adenine with formaldehyde in aqueous solution at room temperature under neutral conditions to form adducts on the 6-amino group and/or the 9-nitrogen atom.Pyruvic acid being a central intermediate in the present metabolism, we studied reactivity of the corresponding aldehyde, pyruvic aldehyde 2 (methylglyoxal), with adenine 1 (Fig. 1) and we are reporting here these results. Pyruvaldehyde could have been produced under prebiotic conditions by retroaldolization from complex mixtures of sugars formed by the formose reaction. It was detected in caramel ( Tomasik et al., 1989) and alkaline decomposition of hexoses such as Image-mannose, Image-xylose and Image-glucose which affords pyruvaldehyde hydrate (Evans, 1942; Feather and Harris, 1973). Such decompositions of sugars could have been a source of various prebiotic molecules like aldehydes and heterocycles.

Careful examination of the present metabolism and in vitro selection of various catalytic RNAs strongly support the “RNA World” hypothesis of the origin of life. However, in this scenario, the difficult prebiotic synthesis of ribose and consequently of nucleotidesnext term remain a major problem. In order to overcome this problem and obtain nucleoside analogs, we are investigating reactions of the nucleic acid base, adenine 1, with different aldehydes under presumably prebiotic conditions. In the reaction of adenine and pyruvaldehyde 2 in water, we report here the formation in high yield of two isomeric products. These compounds possessing alcohols functions as nucleosides result from condensation of two molecules of pyruvaldehyde on the 6-amino group of one adenine molecule.

In prebiotic scenarios biopolymers can be thought of as condensation products of abiotically formed monomers. Polymers (polysaccharides, peptides, and polynucleotides) will not spontaneously form in an aqueous solution from their monomers because of the standard-state Gibbs free-energy change ... In the polymerization process of nucleic acids extant organisms activate the monomers by converting them to phosphorylated derivatives and then utilize the favorable free energy of phosphate hydrolysis to drive the reaction. Does this present day process mimic spontaneously occurring prebiotic reactions, thus representing a sort of biochemiomimesis descending from ancient pathways, or should it be considered a fully novel cellular invention? ... we report the efficient phosphorylation of nucleosides occurring in formamide on numerous phosphate minerals. Consequently, ... activated monomers can form in prebiotic conditions in a liquid, non-aqueous environment in the presence of phosphate minerals in conditions compatible with the thermodynamics of polymerization.

Recent studies have shown how interactions of the ”RNA world’ with lipids may have been mutually beneficial for both vesicle formation and RNA replication (Chen et al., 2004). In lipid vesicles, replicating RNA molecules profit by being segregated away from non-replicating ”free-loading’ RNAs that would otherwise benefit from efficient RNA polymerase action. Conversely, the ability of RNA molecules to replicate would have allowed vesicles to grow through increased osmotic pressure (Chen et al., 2004). In this scheme, the more successful vesicle/replicating RNA combinations would expand the fastest and would thus be more likely to split into daughter vesicles, thereby fulfilling many of the key requirements for the initiation of primordial life.Less progress has been made in showing how mutually beneficial interactions could have arisen between the RNA and early protein world. In vitro selection strategies have shown that RNA molecules are capable of carrying out several steps required for amino acid activation and peptide bond formation (Chapple et al., 2003; Ferreira and Coutinho, 1993; Huang et al., 2000; Johnston et al., 2001; Kumar and Yarus, 2001). However, it is unclear how the acquisition of these enzymic activities would have been subject to immediate selection in the primordial environment (Orgel, 1989).Here I propose a scheme that integrates nucleic acid and protein function in a way that allows the mutual co-evolution of nucleic acid-dependent protein synthesis and nucleic acid-dependent nucleic acid replication. The model proposes a very early association between nucleic acid and protein polymers in the primordial development of life. It suggests a specific role for amyloid; a protein aggregate in which main chain -sheet interactions stabilize the formation of fibres. Predictions from the model are consistent with recently published observations.This proposal differs from the prevailing ”RNA-world’ model of pre-biotic development because it involves proteins interacting with the nucleic acids much earlier in evolution than previously suggested. It is even possible that the first self-replicating RNA molecules evolved in association with protein/amyloid and never existed in isolation. An advantage of this model is that it suggests simple evolutionary paths from amyloid-associated elongase and replicase activities to ribosomes and RNA polymerase respectively. In particular, the elongase activity could act as a focus for incremental selective changes that were necessary for the development of template-directed peptide bond formation, without any one step being contingent on future evolutionary developments (Chapple et al., 2003; Huang et al., 2000; Johnston et al., 2001; Lohse and Szostak, 1996; Nissen et al., 2000; Yarus and Welch, 2000; Zhang and Cech, 1997).

A primordial peptide cycle involving the chemical formation and degradation of peptides has recently been proposed (Huber et al., 2003). Here I argue [insert: -as opposed to showing emperically-]that peptides in solution would be selectively degraded by comparison to those included in amyloid. Mixed chiral peptides are unlikely to have formed amyloid since they have a lower propensity to form -sheet structures (Brack and Barbier, 1990), thus it is likely that amyloid was homochiral and that mixed chiral peptides were selectively degraded and recycled into other random chiral combinations. Base-pairing of nucleic acids during replication has also been argued to promote homochirality (Schoning et al., 2000), leading to the proposal here that both protein and nucleic acid polymers involved in the proposed mechanism were homochiral.There is no a priori reason to believe that any particular homochiral amyloid-nucleic acid combinations (e.g. DD, DL, LD or LL) would have had a selective advantage. [Insert: -and no a priori reason that they would not have either-]Indeed RNA was found to induce the aggregation of both homo L and D poly (Lys-Leu) polypeptides with equal efficiency (Brack and Barbier, 1990). It is therefore possible that all chiral combinations co-existed and competed with each other. The later development of enzymic activities that could direct the synthesis of chiral protein and RNA precursors would then have been the key event in the genesis of the current chiral combination.