Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?

<p>Abstract</p> <p>Background</p> <p>The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO₂producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing proposal that life arose within alkaline (pH 9-11) deep-sea hydrothermal vents like those of the 'Lost City', with the interface with the acidic ocean creating a proton gradient sufficient to drive the first metabolism. However, RNA is most stable at pH 4-5 and is unstable at alkaline pH, raising the possibility that RNA may have first arisen in the acidic ocean itself (possibly near an acidic hydrothermal vent), acidic volcanic lake or comet pond. As the Hadean Eon progressed, the ocean pH is inferred to have gradually risen to near neutral as atmospheric CO₂levels decreased.</p> <p>Presentation of the hypothesis</p> <p>We propose that RNA is well suited for a world evolving at acidic pH. This is supported by the enhanced stability at acidic pH of not only the RNA phosphodiester bond but also of the aminoacyl-(t)RNA and peptide bonds. Examples of <it>in vitro</it>-selected ribozymes with activities at acid pH have recently been documented. The subsequent transition to a DNA genome could have been partly driven by the gradual rise in ocean pH, since DNA has greater stability than RNA at alkaline pH, but not at acidic pH.</p> <p>Testing the hypothesis</p> <p>We have proposed mechanisms for two key RNA world activities that are compatible with an acidic milieu: <it>(i) </it>non-enzymatic RNA replication of a hemi-protonated cytosine-rich oligonucleotide, and <it>(ii) </it>specific aminoacylation of tRNA/hairpins through triple helix interactions between the helical aminoacyl stem and a single-stranded aminoacylating ribozyme.</p> <p>Implications of the hypothesis</p> <p>Our hypothesis casts doubt on the hypothesis that RNA evolved in the vicinity of alkaline hydrothermal vents. The ability of RNA to form protonated base pairs and triples at acidic pH suggests that standard base pairing may not have been a dominant requirement of the early RNA world.</p> <p>Reviewers</p> <p>This article was reviewed by Eugene Koonin, Anthony Poole and Charles Carter (nominated by David Ardell).</p

Evidence from glycine transfer RNA of a frozen accident at the dawn of the genetic code

<p>Abstract</p> <p>Background</p> <p>Transfer RNA (tRNA) is the means by which the cell translates DNA sequence into protein according to the rules of the genetic code. A credible proposition is that tRNA was formed from the duplication of an RNA hairpin half the length of the contemporary tRNA molecule, with the point at which the hairpins were joined marked by the canonical intron insertion position found today within tRNA genes. If these hairpins possessed a 3'-CCA terminus with different combinations of stem nucleotides (the ancestral operational RNA code), specific aminoacylation and perhaps participation in some form of noncoded protein synthesis might have occurred. However, the identity of the first tRNA and the initial steps in the origin of the genetic code remain elusive.</p> <p>Results</p> <p>Here we show evidence that glycine tRNA was the first tRNA, as revealed by a vestigial imprint in the anticodon loop sequences of contemporary descendents. This provides a plausible mechanism for the missing first step in the origin of the genetic code. In 448 of 466 glycine tRNA gene sequences from bacteria, archaea and eukaryote cytoplasm analyzed, CCA occurs immediately upstream of the canonical intron insertion position, suggesting the first anticodon (NCC for glycine) has been captured from the 3'-terminal CCA of one of the interacting hairpins as a result of an ancestral ligation.</p> <p>Conclusion</p> <p>That this imprint (including the second and third nucleotides of the glycine tRNA anticodon) has been retained through billions of years of evolution suggests Crick's 'frozen accident' hypothesis has validity for at least this very first step at the dawn of the genetic code.</p> <p>Reviewers</p> <p>This article was reviewed by Dr Eugene V. Koonin, Dr Rob Knight and Dr David H Ardell.</p

The transition from noncoded to coded protein synthesis: did coding mRNAs arise from stability-enhancing binding partners to tRNA?

<p>Abstract</p> <p>Background</p> <p>Understanding the origin of protein synthesis has been notoriously difficult. We have taken as a starting premise Wolf and Koonin's view that "evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e., in an RNA world containing ribozymes with versatile activities".</p> <p>Presentation of the hypothesis</p> <p>We propose that coded protein synthesis arose from a noncoded process in an RNA world as a natural consequence of the accumulation of a range of early tRNAs and their serendipitous RNA binding partners. We propose that, initially, RNA molecules with 3' CCA termini that could be aminoacylated by ribozymes, together with an ancestral peptidyl transferase ribozyme, produced small peptides with random or repetitive sequences. Our concept is that the first tRNA arose in this context from the ligation of two RNA hairpins and could be similarly aminoacylated at its 3' end to become a substrate for peptidyl transfer catalyzed by the ancestral ribozyme. Within this RNA world we hypothesize that proto-mRNAs appeared first simply as serendipitous binding partners, forming complementary base pair interactions with the anticodon loops of tRNA pairs. Initially this may have enhanced stability of the paired tRNA molecules so they were held together in close proximity, better positioning the 3' CCA termini for peptidyl transfer and enhancing the rate of peptide synthesis. If there were a selective advantage for the ensemble through the peptide products synthesized, it would provide a natural pathway for the evolution of a coding system with the expansion of a cohort of different tRNAs and their binding partners. The whole process could have occurred quite unremarkably for such a profound acquisition.</p> <p>Testing the hypothesis</p> <p>It should be possible to test the different parts of our model using the isolated contemporary 50S ribosomal subunit initially, and then with RNAs transcribed <it>in vitro </it>together with a minimal set of ribosomal proteins that are required today to support protein synthesis.</p> <p>Implications of the hypothesis</p> <p>This model proposes that genetic coding arose <it>de novo </it>from complementary base pair interactions between tRNAs and single-stranded RNAs present in the immediate environment.</p> <p>Reviewers</p> <p>This article was reviewed by Eugene Koonin, Rob Knight and Berthold Kastner (nominated by Laura Landweber).</p

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Making Molecules with Clay: Layered Double Hydroxides, Pentopyranose Nucleic Acids and the Origin of Life

A mixture of sugar diphosphates is produced in reactions between small aldehyde phosphates catalysed by layered double hydroxide (LDH) clays under plausibly prebiotic conditions. A subset of these, pentose diphosphates, constitute the backbone subunits of nucleic acids capable of base pairing, which is not the case for the other products of these LDH-catalysed reactions. Not only that, but to date no other polymer found capable of base pairing&mdash;and therefore information transfer&mdash;has a backbone for which its monomer subunits have a plausible prebiotic synthesis, including the ribose-5-phosphate backbone subunit of RNA. Pentose diphosphates comprise the backbone monomers of pentopyranose nucleic acids, some of the strongest base pairing systems so far discovered. We have previously proposed that the first base pairing interactions were between purine nucleobase precursors, and that these were weaker and less specific than standard purine-pyrimidine interactions. We now propose that the inherently stronger pairing of pentopyranose nucleic acids would have compensated for these weaker interactions, and produced an informational polymer capable of undergoing nonenzymatic replication. LDH clays might also have catalysed the synthesis of the purine nucleobase precursors, and the polymerization of pentopyranose nucleotide monomers into oligonucleotides, as well as the formation of the first lipid bilayers

A ribosome without RNA

It was Francis Crick who first asked why the ribosome contains so much RNA, and discussed the implications of this for the direct flow of genetic information from DNA to protein. Remarkable advances in our understanding of the ribosome and protein synthesis, including the recent publication of two mammalian mitochondrial ribosome structures, have shed new light on this intriguing aspect of evolution in molecular biology. We examine here whether RNA is indispensable for coded protein synthesis, or whether an all-protein ‘ribosome’ (or ‘synthosome’) might be possible, with a protein enzyme catalyzing peptide synthesis, and release factor-like protein adaptors able to read a message composed of deoxyribonucleotides. We also compare the RNA world hypothesis with the alternative ‘proteins first’ hypothesis in terms of their different understandings of the evolution of the ribosome, and whether this might have been preceded by an ancestral form of nonribosomal peptide synthesis catalyzed by protein enzymes