The Bigger Question -WHO WON THE EVOLUTIONARY RACE -DNA or RNA? (Theories & Experimental Evidences)Abstract :The historical existence of the RNA world, in which early life used RNA for both genetic information and catalytic ability, is widely accepted. However, there has been little discussion of whether protein synthesis arose before DNA or what preceded the RNA world (i.e. the pre-RNA world). We outline arguments of what route life may have taken out of the RNA world: whether DNA or protein followed.
Metabolic arguments favor the possibility that RNA genomes preceded the use of DNA as the informational macromolecule. However, the opposite can also be argued based on the enhanced stability, reactivity, and solubility of 2-deoxyribose as compared to ribose. The possibility that DNA may have come before RNA is discussed, although it is a less parsimonious explanation than DNA following RNA.Introduction:One of the most important questions facing the study of the origin of life is the nature of the rst genetic material.
It is usually stated that the transition from non-life to life occurred when this genetic material began to accumulate and replicate in the primitive environment. The importance of RNA in the origin of life has been asserted by so many researchers for so many years that it has been generally assumed that RNA was among the rst informational polymers (see for example, Belozerskii, 1959; Brachet, 1959; Oparin, 1961; Rich, 1962; Buchanan, 1965; Haldane, 1965; Woese, 1967; Crick, 1968; Orgel, 1968; Kuhn, 1972; Eigen and Schuster, 1979; White III, 1982). The RNA world is a hypothetical period of the early biosphere when both the information needed for life and the enzymatic activity of living organisms were con- tained in RNA molecules (Gilbert, 1986; Joyce, 2002).This proposal stems from the discovery of catalytic activity in RNA (Cech et al., 1981; Guerrier-Takada et al., 1983), and it has often been cited as the solution to the problem of whether life rst arose as DNA or protein. The RNA world and its catalytic repertoire have been extensively discussed (Orgel, 1986; Beaudry and Joyce, 1992; Piccirilli et al., 1990; Szostak and Ellington, 1993; Ellington, 1994; Gesteland and Atkins, 1993; Joyce, 1998, 2002). There has been some discussion about the transition from the pre-RNA world into the RNA world (Orgel, 1986, 1989; Schwartz et al., 1987; Joyce, 1989; de Duve, 1993; Piccirilli, 1995; Miller, 1997).The possibilities of a simultaneous origin of RNA and DNA (Orlo and Stephen-Sherwood, 1974) or of DNA before proteins (Benner et al., 1987, 1989, 1993) have also been addressed. As summarized by Kumar and Yarus (2001) there is an increasing amount of experimental evidence suggesting that protein synthesis evolved in an RNA world. However, very little has been said about the transition from the RNA world to the modern world of DNA/RNA/protein (where DNA stores the information, RNA serves auxiliary functions, and protein does the catalysis). The primary focus has been based on the observations on the importance of RNA, including the RNA primer involved in DNA replication, the assumption of the lateness of DNA as a more stable archive of genetic information (Ferris and Usher, 1983; Lazcano et al., 1988a,b, 1992; Benner et al., 1989; Poole et al., 2000), and the study of the evolution of ribonucleotide reductases as an essential step in the transition from the RNA to the extant DNA/RNA/ protein world (Follmann, 1982; Harder, 1993; Reichard, 1993; Freeland et al., 1999). The hypothesis that the RNA world, which may have been preceded by simpler living entities, eventually evolved into the DNA/protein world which had all the characteristics of modern biochemistry, is currently the most favored one. However, there are other alternatives. The purpose of this paper is to discuss these other possibilities. In this paper we address the possibility that deoxyribose came before ribose, and then whether DNA came before protein synthesis or the reverse. Other aspects of this question have been discussed by Freeland et al. (1999). We also examine the various ways to shift from the pre-RNA world to the RNA world, including the possibility that DNA came before RNA. Although we agree that the most parsimonious interpretation of the available evidence favors the precedence of RNA over proteins and DNA, it is also true that evolution does not always follow the straightest course. The discussion presented here is clearly speculative, but it is hoped that it will be a guide for further experiments.Which is more ancient: DNA or RNA?Woese (1967) rst suggested that DNA may have been more abundant in the prebiotic environment than RNA due to the greater stability of DNA in mildly basic conditions, postulated to have been caused primarily by an ammonia-rich ocean and by the weathering of basic rocks. In addition to the replicative ability, catalytic proper- ties, and the central role in biochemistry of RNA, the existence of the RNA world has been based on several metabolic arguments (Eigen et al., 1981; White III, 1982; Ferris and Usher, 1983; Lazcano et al., 1988a,b, 1992; Joyce, 1989; Ellington, 1993; Schwartz, 1993; James and Ellington, 1995; Bloch, 1996) such as the biosyntheses of histidine, deoxyribonucleotides, and deoxythymidine. However, none of these are compelling reasons for the precedence of RNA over DNA. DNA can certainly act as a template for its replication and with the experi- mental development of deoxyribozymes, DNA has joined the ranks of catalytic species. No natural DNA enzymes have been described, perhaps because the early appearance of ribozymes diminished the likelihood of additional catalytic nucleic acids. The importance of DNA in cellular function as the repository of genetic information could be interpreted as a central and thus ancient” biological process. While RNA is more versatile and performs more of these functions [e.g. RNA is a primer for DNA replication (Eigen et al., 1981) and is central to ribosome function (Noller et al., 1992; Ban et al., 2000; Nissen et al., 2000)], it can only be said that RNA played an important role before the last common ancestor (Tekaia et al., 1999; Delaye and Lazcano, 2000; Lazcano Araujo, 2001; Anantharaman et al., 2002), but it cannot be said what preceded it. The presence of ribose as a component of many coenzymes is a powerful argument for the importance of RNA monomers and dimers early in evolution. It cannot be said if these metabolic fossils are remnants of excised genetic or catalytic material. While coenzymes can be viewed as molecular fossils of ancient metabolic systems, they are not necessarily fossils of the rst metabolic system. Since each genetic takeover at least partially overprints pathways from the previous system, coenzymes are more likely remnants of the system just before DNA/protein than of earlier pre-RNA systems. This argument holds not only for molecular fossils and for biosynthetic pathways, but also for DNA replication, translation, and all other cellular mechanisms. The biosynthetic arguments are entirely derived from complicated modern metabolic pathways. These path- ways could have easily overprinted older ones as environmental conditions around these ancient organisms changed. While it has been stated that recent features of metabolism are superimposed on remnants of ancient life (Benner et al., 1989), the overprinted metabolism may obscure or obliterate the message of the previous pathway. Of course, if the metabolic pathways evolved backwards (Horowitz, 1945) then the biosynthesis of 2-deoxyribose from ribose would suggest that RNA came from DNA (Ferris and Usher, 1983). One would expect that even the primitive pre-RNA catalysts would be more efcient and selective than any abiotic chemistry going on around them. However, these early catalysts were probably much slower and less selective than modern enzymes. Thus, ideas of what ingredients could be used in early life shifts from ease of synthesis to ease of incorporation, versatility, stability, and reactivity.The prebiotic availability of deoxyriboseAre there any arguments that could be used to favor the existence of a DNA world (devoid of proteins) over the most familiar RNA world? The prebiotic synthesis of deoxyribose from glyceraldehyde and acetaldehyde is poor (Or!o and Cox, 1962), but the prebiotic synthesis of ribose is not vastly better (Shapiro, 1988). There are other potential prebiotic pathways being explored for the synthesis of ribose from small phosphorylated aldehydes in the presence of hydroxide minerals under neutral conditions (Krishnamurthy et al., 1999), but equivalent pathways to 2-deoxyribose have not been studied. Although sugars are currently out of favor as prebiotic reagents, the presence of sugar acids, including both ribosugar- and deoxysugar acids in the 4.6109 years old Murchison meteorite suggest that they may have been present in the primitive Earth, derived from the accretion of extraterrestrial sources (Cooper et al., 2001) or from endogenous processes involving formal- dehyde and its derivatives. It has been argued (Robertson and Miller, 1995; Robertson et al., 1996) that drying lagoon conditions could have acted as a prebiotic reactor. The solubility of 2-deoxyribose is 30 molal (Dworkin, 1997) while ribose is 20 molal (Goldberg and Tewari, 1989) at 25 C. The greater solubility of 2-deoxyribose would be a slight advantage in a drying scenario for the synthesis of nucleosides or their precursors (Fuller et al., 1972a,b). 2-Deoxyribose may have been more reactive under prebiotic conditions: for example it reacts about 150 times faster than ribose with the alternative base urazole to form the nucleoside at 25 C(Dworkin and Miller, 2000). In addition, Larralde et al. (1995) have shown that 2-deoxyribose decomposes 2.6 times more slowly than does ribose at 100C. Other advantages of DNA over RNA are that it has one fewer chiral center, has greater stability at the pH of the current ocean (8.2), and does not has the 2050 and 3050 ambiguity in polymerizations.Formation of thymine from uracil:As we have seen, RNAs occupy a pivotal role in the cell metabolism of all living organisms and several biochemical observations resulting from the study of contemporary metabolism should be stressed. For instance, throughout its life cycle, the cell produces deoxyribonucleotides required for the synthesis of DNA that derive from ribonucleotides of the RNA. Thymine, a DNA specic base is obtained by transformation (methylation) of uracil a RNA specic base, and RNAs serve as obligatory primers during DNA synthesis (Fig. 6.5). Finally, the demonstration that RNAs act as catalysts is an additional argument in favour of the presence of RNAs before DNA during evolution.Stability of DNA and RNA:DNA replication triggered by ribonucleotide primers can be considered as a modied transcription process during which polymerisation of RNA is replaced by that of DNA. In addition, DNA a double-stranded molecule lacking a hydroxyl group in 2′ of the deoxyfuranose, appears more stable than RNA. Therefore it seems highly likely that RNA arose before DNA during biochemical evolution, and for this reason DNA is sometimes considered as modied RNA better suited for the conservation of genetic information. This genetic privilege would constitute a logical step in an evolutionary process during which other molecules could have preceded RNA and transmitted genetic information. The idea of an RNA world rests primarily on three fundamental hypotheses, developed by Joyce and Orgel (1999):” during a certain period in evolution, genetic continuity was assured by RNA replication,” replication was based on Watson”Crick type base pairing, ” genetically coded proteins were not involved in catalysis.Conclusion:Of the two major classes of informational macromolecules in the present day cells (nucleic acid and proteins), only nucleic acids are capable of directing their own self replication. Nucleic acids can serve as templates for their own synthesis as a result of specific base pairing between complementary nucleotides. A critical step in understanding molecular evolution was thus reached in early 1980s, when it was discovered in laboratories of Sid Altman and Tom Cech that RNA was capable of catalyzing a number of chemical reactions , including the polymerization of nucleotide. Further studies have extended, including the description of RNA molecules that direct synthesis of a new RNA stand from an RNA template and consequently RNA is generally believed to have the initial genetic system and early stage of chemical evolution is thought to have been based on self-replicating RNA molecule. Ordered interaction between the RNA and the amino acids have evolved into present day genetic code, and the DNA eventually replaced RNA as the genetic material.The first cell is presumed to have risen by enclosure of self-relpicating RNA in a membrane composed of phospholipids.Reference:Anantharaman, V., Koonin, E.V., Aravind, L., 2002. Comparative genomics and evolution of proteins involved in RNA metabolism. 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