Natural Selection, Protein Engineering, and the Last Riboorganism: Rational Model Building in Biochemistry

Benner, Steven A.; Allemann, Rudolf Konrad; Ellington, Andrew D.; Ge, Liang; Glasfeld, Arthur; Leanz, G. F.; Krauch, Tilman; MacPherson, Lawrence; Moroney, Simon E.; Piccirilli, Joseph A.; Weinhold, Elmar G.

doi:10.1101/sqb.1987.052.01.009

Cited by 62 publications

(45 citation statements)

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“…The involvement of amino acids attached to tRNA in all manner of metabolic process has often been used to argue that these are relics of an RNA world of complex metabolism (Di Giulio 1997), for example the use of glutamyl-tRNA in the synthesis of chlorophyll and bacteriochlorophyll (Benner et al 1987). This is a remarkably weak and insubstantial argument.…”

Section: Discussionmentioning

confidence: 99%

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Obcells as Proto-Organisms: Membrane Heredity, Lithophosphorylation, and the Origins of the Genetic Code, the First Cells, and Photosynthesis

Cavalier‐Smith

2001

Journal of Molecular Evolution

141

130

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Abstract. I attempt to sketch a unified picture of the origin of living organisms in their genetic, bioenergetic, and structural aspects. Only selection at a higher level than for individual selfish genes could power the cooperative macromolecular coevolution required for evolving the genetic code. The protein synthesis machinery is too complex to have evolved before membranes. Therefore a symbiosis of membranes, replicators, and catalysts probably mediated the origin of the code and the transition from a nucleic acid world of independent molecular replicators to a nucleic acid/protein/lipid world of reproducing organisms. Membranes initially functioned as supramolecular structures to which different replicators attached and were selected as a higher-level reproductive unit: the proto-organism. I discuss the roles of stereochemistry, gene divergence, codon capture, and selection in the code's origin. I argue that proteins were primarily structural not enzymatic and that the first biological membranes consisted of amphipathic peptidyl-tRNAs and prebiotic mixed lipids. The peptidyl-tRNAs functioned as genetically-specified lipid analogues with hydrophobic tails (ancestral signal peptides) and hydrophilic polynucleotide heads. Protoribosomes arose from two cooperating RNAs: peptidyl transferase (large subunit) and mRNA-binder (small subunit). Early proteins had a second key role: coupling energy flow to the phosphorylation of gene and peptide precursors, probably by lithophosphorylation by membrane-anchored kinases scavenging geothermal polyphosphate stocks. These key evolutionary steps probably occurred on the outer surface of an 'inside out-cell' or obcell, which evolved an unambiguous hydrophobic code with four prebiotic amino acids and proline, and initiation by isoleucine anticodon CAU; early proteins and nucleozymes were all membrane-attached. To improve replication, translation, and lithophosphorylation, hydrophilic substrate-binding and catalytic domains were later added to signal peptides, yielding a ten-acid doublet code. A primitive proto-ecology of molecular scavenging, parasitism, and predation evolved among obcells. I propose a new theory for the origin of the first cell: fusion of two cup-shaped obcells, or hemicells, to make a protocell with double envelope, internal genome and ribosomes, protocytosol, and periplasm. Only then did water-soluble enzymes, amino acid biosynthesis, and intermediary metabolism evolve in a concentrated autocatalytic internal cytosolic soup, causing 12 new amino acid assignments, termination, and rapid freezing of the 22-acid code. Anticodons were recruited sequentially: GNN, CNN, INN, and *UNN. CO 2 fixation, photoreduction, and lipid synthesis probably evolved in the protocell before photophosphorylation. Signal recognition particles, chaperones, compartmented proteases, and peptidoglycan arose prior to the last common ancestor of life, a complex autotrophic, anaerobic green bacterium.

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Section: Discussionmentioning

confidence: 99%

“…First is the assumption of an RNA world able to mediate complex metabolism (Gilbert 1986;Benner et al 1987;Gibson and Lamond 1990). I very much doubt that such a world ever existed.…”

Section: Discussionmentioning

confidence: 99%

Obcells as Proto-Organisms: Membrane Heredity, Lithophosphorylation, and the Origins of the Genetic Code, the First Cells, and Photosynthesis

Cavalier‐Smith

2001

Journal of Molecular Evolution

141

130

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“…Many of these speculations consider genetic structure to the exclusion of most other biochemical data in modeling the "RNA world" (2-5). As discussed elsewhere, this narrow focus leads to interesting but often chemically and biologically implausible models (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

“…The considerations described above allow us to begin to construct a model that assigns biochemical traits to the breakthrough organism. At (8). ]…”

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confidence: 99%

Modern metabolism as a palimpsest of the RNA world.

Benner

Ellington

Tauer

1989

Proc. Natl. Acad. Sci. U.S.A.

430

324

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An approach is developed for constructing models of ancient organisms using data from metabolic pathways, genetic organization, chemical structure, and enzymatic reaction mechanisms found in contemporary organisms. This approach is illustrated by a partial reconstruction of a model for the "breakthrough organism," the last organism to use RNA as the sole genetically encoded biological catalyst. As reconstructed here, this organism had a complex metabolism that included dehydrogenations, transmethylations, carboncarbon bond-forming reactions, and an energy metabolism based on phosphate esters. Furthermore, the breakthrough organism probably used DNA to store genetic information, biosynthesized porphyrins, and used terpenes as its major lipid component. This model differs significandy from prevailing models based primarily on genetic data.Since the discovery of self-splicing RNA (1), molecular biology has become the central focus of speculation concerning early forms of life. Many of these speculations consider genetic structure to the exclusion of most other biochemical data in modeling the "RNA world" (2-5). As discussed elsewhere, this narrow focus leads to interesting but often chemically and biologically implausible models (6-10).We develop here an alternative approach for generating experimentally testable models of the RNA world, based on metabolic, structural, and mechanistic data from contemporary organisms. Several specific "paradigms," problem solutions covering individual topics in biochemical evolution, are constructed by this approach. These paradigms demonstrate the utility of this broader view and provide elements of a framework for interpreting the "historical" component of modern biochemistry (11).We begin by assuming that life on earth passed through three episodes ( Fig. 1) (12). In the first (the RNA world) (13), RNA was the only genetically encoded component of biological catalysts. The second episode began with the invention of translation-based synthesis of proteins in a "breakthrough organism," the first organism to contain a genetically encoded messenger RNA that directed the synthesis of a protein selectable for its catalytic activity. The third episode comprises the divergent evolution of the "progenote," the most recent common ancestor of all modern forms of life.a This model views modern macromolecular catalysis as a "palimpsest" of an earlier metabolic state, with features that arose recently ("derived traits") superimposed upon features that are remnants of ancient life ("primitive traits"). (A palimpsest is a parchment that has been inscribed two or more times, with the previous texts imperfectly erased and therefore still partially legible.) To describe the biochemistry of these ancient organisms, we must first examine contemporary biochemical traits to distinguish ancient information from information added later. These descriptions are prerequisites for descriptions ofthe development ofmetabolism, the origin of translation, and other events that occurred in the RNA world....

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“…Numerous examples exist where nucleic acids have been selected as aptamers for proteins or small molecules (5-7), as well as for chemical manipulations, including those of nucleic acid ligases and polymerases (8). Nevertheless, the functional scope of nucleic acids is likely limited since they possess a narrow range of functionality, at least when compared with proteins (9,10). Those functionalities that nucleic acids contain are principally employed in WatsonCrick base pairing, leaving sugar hydroxyls (in the case of RNA) or charged phosphodiesters available to participate in binding or catalysis.…”

Section: Introductionmentioning

confidence: 99%

Expanding the structural and functional diversity of RNA: analog uridine triphosphates as candidates for in vitro selection of nucleic acids

Vaish

Fraley²,

Szostak³

et al. 2000

Nucleic Acids Research

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Two analog uridine triphosphates tethering additional functionality, one a primary amino group and the second a mercapto group, were prepared and tested for their compatibility with in vitro RNA selection procedures. 5-(3-Aminopropyl)uridine triphosphate (UNH 2 ) as a uridine substitute was a more effective substrate for T7 RNA polymerase than 5-(2-mercaptoethyl)uridine triphosphate (USH). However, both functioned in transcription assays of 100 nt templates to generate RNA transcripts in quantities sufficient to initiate RNA selection procedures. Transcription of RNA pools with T7 RNA polymerase and UNH 2 or USH occurred with efficiencies of 43 and 29%, respectively, of the values obtained for native UTP transcription. In addition, the transcribed RNA containing roughly 25% UNH 2 residues exhibited better substrate properties for SuperScript™ II RNase H reverse transcriptase than did RNA transcripts containing~25% of the USH analog. With either analog, both transcription and reverse transcription proceeded with high fidelity for insertion of the analog residue.

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Natural Selection, Protein Engineering, and the Last Riboorganism: Rational Model Building in Biochemistry

Cited by 62 publications

References 0 publications

Obcells as Proto-Organisms: Membrane Heredity, Lithophosphorylation, and the Origins of the Genetic Code, the First Cells, and Photosynthesis

Obcells as Proto-Organisms: Membrane Heredity, Lithophosphorylation, and the Origins of the Genetic Code, the First Cells, and Photosynthesis

Modern metabolism as a palimpsest of the RNA world.

Expanding the structural and functional diversity of RNA: analog uridine triphosphates as candidates for in vitro selection of nucleic acids

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