The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Title: In Vitro Selected Ribozymes
Author: Ulrich F. Müller
Affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, USA
Abstract: The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genomes and as the only genome-encoded catalyst. This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory, for a wide range of reactions that might have been used by RNA world organisms. The focus of this review is to: summarize which ribozymes have been generated in the lab; describe some of their selection procedures; briefly discuss their relevance to RNA world scenarios; and to describe what future developments are required to generate an RNA world organism in the lab.
Title: Acytota: Neglected Kingdom of Life
Authors: Edward N. Trifonov 1 and Eduard Kejnovsky 2
Affiliation: 1 Genome Diversity Center, Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel
2 Department of Plant Developmental Genetics, Institute of Biophysics ASCR, Kralovopolska 135, 61265 Brno, Czech Republic
Abstract: There is a huge variety of RNA- and DNA-containing entities which multiply within and propagate between cells of all kingdoms of life, having no cells of their own. Apart of cellular organisms these entities (viroids, plasmids, mobile elements, viruses and others) are the only ones which have their distinct genetic identities, but not included in any kingdom of life, since all the traditional kingdoms are cellular. We suggest to introduce the distinct category of the acellular organisms, Acytota, as an additional, undeservedly ignored kingdom of life. Acytota are indispensable for cellular life and its evolution. Six traditional kingdoms (Cytota) together with Acytota complete the classification of biological world (Biota), leaving nothing life-like beyond.
Title: The Proto-Ribosome within the Modern Ribosome—the Symmetrical Region, Its Extended Form or Its Core?
Author: Ilana C. Agmon 1,2
Affilistion:1 Institute for Advanced Studies in Theoretical Chemistry, Schulich Faculty of Chemistry—Technion—Israel Institute of Technology, Haifa 32000, Israel
2 Fritz Haber Research Center for Molecular Dynamics, Hebrew University, Jerusalem, 91904, Israel
Abstract: The vestige of the proto-ribosome is believed to be still embedded in the contemporary ribosome, assembling the site of peptide bond formation. Three concentric structural elements of different magnitudes, namely, the entire symmetrical region of the large subunit, its core and an extended version of it, were suggested to constitute the vestiges of the proto-ribosome, which could have materialized spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and simple elongation. Probabilistic considerations are applied in order to compare the adequacy of the three candidates to be the initial proto-ribosome to emerge. The analysis points to the dimeric proto-ribosome, a dimer of two tRNA-like molecules constituting the core of the symmetrical region, as being the vestige of the initial proto-ribosome within the contemporary ribosome. Moreover, analysis suggests that this simple apparatus had a reasonable probability of random emergence in the prebiotic era, offering a feasible starting point for a continuous evolutionary path leading from the prebiotic matter into the intricate modern translation system.
Title: The Origin and Evolution of Ribonucleotide Reduction—A Repeated History of Reciprocal Dependencies
Authors: Daniel Lundin 1, Gustav Berggren 1, David Nord 1, Derek Logan 2 and Britt-Marie Sjöberg 1
Affiliations: 1 Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden
2 Department of Biochemistry and Structural Biology, Lund University, Box 124, SE-221 00 Lund, Sweden
Abstract: Ribonucleotide reduction is the only pathway for de novo synthesisof deoxyribonucleotides in extant organisms. Ribonucleotide reductase (RNR) catalyses the reaction, which is chemically demanding and involves a carbon-based radical. The mechanism has been deemed unlikely to be catalysed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesised at the transition from RNA to DNA encoded genomes. While it is entirely possible that a different pathway was used, later to be replaced with the extant mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA+protein world and suggest a model for a proto typical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to extant RNRs, the urRNR, which diversified to the extant three classes characterised mainly by how the radical is initially generated. Subsequent to the origin of the three classes, RNRs have undergone further specialisations, and we describe a phylogenetic subclassification of the enzyme family. RNR genes are frequent hosts of selfish genetic elements—introns and inteins—and we observe an interesting organism distribution of classes and subclasses indicating both short and long-range horizontal transfer of RNR genes.
Title: Characterization of RNA-like oligomers from lipid-assisted nonenzymatic synthesis: Implications for origin of informational molecules in the RNA world
Authors: Chaitanya Mungi 1 and Sudha Rajamani 1,*
Affiliation: Indian Institute of Science Education and Research, Pune, Maharashtra 411008 India
Abstract: Formation of informational molecules is a crucial step in the origin of life. In modern biology, fundamental functions like information storage and catalysis are carried out by specialized polymers, whose polymerization is orchestrated by enzymes that use activated monomers. However, prebiotic polymerization had to be a nonenzymatic chemically driven process that used non-activated monomers. Chemical polymerization of monomers is the result of a condensation reaction; an uphill event which is particularly favored in scenarios that push reaction regimes far from equilibrium conditions. Dehydration-rehydration (DH-RH) cycles are one such regime which is thought to have been common on prebiotic Earth. These would have been prevalent in niches like inter-tidal and geothermal pools, which would have been driven by day-night cycles and seasonal variations. In the present study, we undertook detailed characterization of reaction conditions under which lipid-assisted nonenzymatic polymerization of nucleoside 5’-monophosphates is optimum. In addition, the resultant products were characterized using biochemical methods to delineate their chemical makeup and understand the plausible reaction mechanism that drove their formation. Importantly, our study demonstrates that the resultant RNA-like oligomers have abasic sites which result from low pH and high temperatures that drive these uphill reactions; conditions encountered in acidic geothermal pools. In other words, these RNA-like oligomers lack information carrying capability because of loosing most of their heterocyclic bases during the reaction process. Interestingly, sugar-phosphate backbones however readily form under these reaction conditions when ribose 5’-monophosphate is used as the starting monomer. Formation of such backbones would have permitted sampling of a large variety of bases on a preformed polymer backbone. Our results support what is increasingly considered to be a more prebiotically realistic scenario for the origin of the RNA world as it is thought that the native bases in extant biology (A, U/T, G and C) may actually have resulted from fine tuning of a chemical evolutionary process. And, very early on in this process, primordial informational polymers would have utilized simpler bases that might have conferred greater N-glycosyl bond stability; a feature crucial for information propagation in low pH and high temperature regimes of early Earth.
Title: How Amino Acids and Peptides Shaped the RNA world
Authors: Peter van der Gulik and Dave Speijer
Affiliation: Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
Abstract: The “RNA world” hypothesis is seen as one of the main contenders for a viable theory on the origin of life. Relatively small RNAs have catalytic power, RNA is everywhere in present-day life, the ribosome is seen as a ribozyme, and rRNA and tRNA are crucial for modern protein synthesis. However, this view may be incomplete.The modern protein-RNA ribosome, though at its core an RNA structure, possibly started out with amino acids and tiny peptides playing an essential role. The ancient peptidyl transferase center might have emerged in close connection with ancient aminoacylated tRNAs. Small RNAs and amino acids, as well as tiny peptides, probably coevolved. Remember, it is the amino group of aminoacylated tRNA that attacks peptidyl-tRNA destroying the bond between peptide and tRNA. This activity of the amino acid part of aminoacyl-tRNA illustrates the centrality of amino acids in life. With the rise of the “RNA world” view of early life, the pendulum seems to have swung too much towards the ribozymatic part of early biochemistry. The necessary presence and activity of amino acids and peptides is in need of highlighting. In this article, we try to bring the role of the peptide component of earlylife back into focus. We argue that an RNA world independent of amino acids never existed.