Can the RNA World Still Function without Cytidine?

2019 ◽  
Vol 37 (1) ◽  
pp. 71-83
Author(s):  
Andrew S Tupper ◽  
Ralph E Pudritz ◽  
Paul G Higgs
Keyword(s):  
Secondary Structure ◽  
Structure Formation ◽  
Origin Of Life ◽  
Rna World ◽  
Information Storage ◽  
Specific Site ◽  
Rna Sequences ◽  
Secondary Structure Formation ◽  
The Origin Of Life ◽  
Rule Out

Abstract Most scenarios for the origin of life assume that RNA played a key role in both catalysis and information storage. The A, U, G, and C nucleobases in modern RNA all participate in secondary structure formation and replication. However, the rapid deamination of C to U and the absence of C in meteorite samples suggest that prebiotic RNA may have been deficient in cytosine. Here, we assess the ability of RNA sequences formed from a three-letter AUG alphabet to perform both structural and genetic roles in comparison to sequences formed from the AUGC alphabet. Despite forming less thermodynamically stable helices, the AUG alphabet can find a broad range of structures and thus appears sufficient for catalysis in the RNA World. However, in the AUG case, longer sequences are required to form structures with an equivalent complexity. Replication in the AUG alphabet requires GU pairing. Sequence fidelity in the AUG alphabet is low whenever G’s are present in the sequence. We find that AUG sequences evolve to AU sequences if GU pairing is rare, and to RU sequences if GU pairing is common (R denotes A or G). It is not possible to conserve a G at a specific site in either case. These problems do not rule out the possibility of an RNA World based on AUG, but they show that it wouldbe significantly more difficult than with a four-base alphabet.

scholarly journals Are Scientific Models of Life Testable? A Lesson from Simpson’s Paradox

Sci ◽  
2020 ◽  
Vol 2 (3) ◽  
pp. 73
Author(s):  
Prasanta S. Bandyopadhyay ◽  
Nolan Grunska ◽  
Don Dcruz ◽  
Mark C. Greenwood
Keyword(s):  
Origin Of Life ◽  
Rna World ◽  
Scientific Models ◽  
Scientific Model ◽  
Simpson’S Paradox ◽  
World Theory ◽  
Life Issues ◽  
The Origin Of Life ◽  
Logical Sense ◽  
Simpson's Paradox

We address the need for a model by considering two competing theories regarding the origin of life: (i) the Metabolism First theory and (ii) the RNA World theory. We discuss two inter-related points. (I) Models are valuable tools in understanding both the processes and intricacies of the origin of life issues. (II) Insights from models also help us to evaluate the core objection to origin of life theories called “the inefficiency objection” commonly raised by proponents of both the Metabolism First theory and the RNA World theory against each other. We use Simpson’s paradox as a tool for challenging this objection. We will use models in various senses ranging from taking them as representations of reality to treating them as theories/accounts that provide heuristics for probing reality. In this paper, we will frequently use models and theories interchangeably. Additionally, we investigate Conway’s Game of Life and contrast it with our Simpson’s Paradox (SP)-based approach to emergence of life issues. Finally, we discuss some of the consequences of our view. A scientific model is testable in three senses: (i) a logical sense, (ii) a nomological sense, and (iii) a current technological sense. The SP-based model is testable in the logical sense. It is also testable nomologically. However, it is not currently feasible to test it.

The Gibbs adsorption isotherm provides information on the secondary structure formation of amphiphilic peptides

Peptides 1992 ◽  
1993 ◽  
pp. 113-114
Author(s):  
Anna Seelig ◽  
Thomas Alt ◽  
Lothar Kürz ◽  
Manfred Mutter
Keyword(s):  
Secondary Structure ◽  
Adsorption Isotherm ◽  
Structure Formation ◽  
Amphiphilic Peptides ◽  
Secondary Structure Formation

Condensation Reactions Synthesize Random Polymers

2019 ◽  
Author(s):  
David Ross
Keyword(s):  
Origin Of Life ◽  
Rna World ◽  
Functional Polymers ◽  
Peptide Bonds ◽  
Individual Molecular Species ◽  
Condensation Reactions ◽  
Past Half Century ◽  
Working Together ◽  
The Origin Of Life ◽  
The Individual

Over the past half century of serious research on the origin of life, several schools of thought have emerged that focus on “worlds” and what came first in the pathway to the origin of life. One example is the RNA World, a term coined by Walter Gilbert after the discovery of ribozymes. Other examples include the Iron-Sulfur World of Günther Wächtershäuser and the Lipid World proposed by Doron Lancet and coworkers. Then we have a competition between “metabolism first” and “replication first” schools. The worlds and schools have the positive effect of sharpening arguments and forcing us to think carefully, but they also can lock researchers into defending their individual approaches rather than looking for patterns in a larger perspective. One of the main themes of this book is the notion that the first living cells were systems of functional polymers working together within membranous compartments. Therefore, it is best not to think of “worlds” and “firsts” as fundamentals but instead as components evolving together toward the assembly of an encapsulated system of functional polymers. At first the polymers will be composed of random sequences of their monomers, and the compartments will contain random assortments of polymers. Here, we refer to these structures as protocells which are being produced in vast numbers as they form and decompose in continuous cycles driven by a variety of impinging, free-energy sources. This chapter describes how thermodynamic principles can be used to test the feasibility of a proposed mechanism by which random polymers can be synthesized. There is a current consensus that early life may have passed through a phase in which RNA served as a ribozyme catalyst, as a replicating system, and as a means for storing and expressing genetic information. For this reason, we will use RNA as a model polymer, but condensation reactions also produce peptide bonds and oligopeptides. At some point in the evolutionary steps leading to life, peptides and RNA formed complexes with novel functional properties beyond those of the individual molecular species.

scholarly journals In vitro selection of ribozyme ligases that use prebiotically plausible 2-aminoimidazole–activated substrates

2020 ◽  
Vol 117 (11) ◽  
pp. 5741-5748 ◽  
Author(s):  
Travis Walton ◽  
Saurja DasGupta ◽  
Daniel Duzdevich ◽  
Seung Soo Oh ◽  
Jack W. Szostak
Keyword(s):  
Origin Of Life ◽  
In Vitro Selection ◽  
Random Sequence ◽  
Bond Formation ◽  
Rna Sequences ◽  
Phosphodiester Bond ◽  
Complex Protein ◽  
The Origin Of Life ◽  
Group 2

The hypothesized central role of RNA in the origin of life suggests that RNA propagation predated the advent of complex protein enzymes. A critical step of RNA replication is the template-directed synthesis of a complementary strand. Two experimental approaches have been extensively explored in the pursuit of demonstrating protein-free RNA synthesis: template-directed nonenzymatic RNA polymerization using intrinsically reactive monomers and ribozyme-catalyzed polymerization using more stable substrates such as biological 5′-triphosphates. Despite significant progress in both approaches in recent years, the assembly and copying of functional RNA sequences under prebiotic conditions remains a challenge. Here, we explore an alternative approach to RNA-templated RNA copying that combines ribozyme catalysis with RNA substrates activated with a prebiotically plausible leaving group, 2-aminoimidazole (2AI). We applied in vitro selection to identify ligase ribozymes that catalyze phosphodiester bond formation between a template-bound primer and a phosphor-imidazolide–activated oligomer. Sequencing revealed the progressive enrichment of 10 abundant sequences from a random sequence pool. Ligase activity was detected in all 10 RNA sequences; all required activation of the ligator with 2AI and generated a 3′-5′ phosphodiester bond. We propose that ribozyme catalysis of phosphodiester bond formation using intrinsically reactive RNA substrates, such as imidazolides, could have been an evolutionary step connecting purely nonenzymatic to ribozyme-catalyzed RNA template copying during the origin of life.

scholarly journals Solvent viscosity facilitates replication and ribozyme catalysis from an RNA duplex in a model prebiotic process

2019 ◽  
Vol 47 (13) ◽  
pp. 6569-6577 ◽  
Author(s):  
Christine He ◽  
Adriana Lozoya-Colinas ◽  
Isaac Gállego ◽  
Martha A Grover ◽  
Nicholas V Hud
Keyword(s):  
Information Transfer ◽  
Rna World ◽  
Hammerhead Ribozyme ◽  
Information Storage ◽  
Additional Challenge ◽  
The Origin Of Life ◽  
World Hypothesis ◽  
Synthesis Reactions ◽  
Rna World Hypothesis ◽  
Single Sequence

Abstract The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming ‘the strand inhibition problem'. Here, we demonstrate that the same approach allows simultaneous information transfer from both strands of long duplex templates. An additional challenge for the RNA World is that structured RNAs (like those with catalytic activity) function poorly as templates in model prebiotic RNA synthesis reactions, raising the question of how a single sequence could serve as both a catalyst and as a replication template. Here, we show that a viscous solvent also facilitates the transition of a newly synthesized hammerhead ribozyme sequence from its inactive, duplex state to its active, folded state. These results demonstrate how fluctuating environmental conditions can allow a ribozyme sequence to alternate between acting as a template for replication and functioning as a catalyst, and illustrate the potential for temporally changing environments to enable molecular processes necessary for the origin of life.

Secondary structure formation in N-substituted peptides*

2009 ◽  
Vol 51 (1) ◽  
pp. 19-28 ◽  
Author(s):  
KERSTIN MÖHLE ◽  
HANS-JÖRG HOFMANN
Keyword(s):  
Secondary Structure ◽  
Structure Formation ◽  
Secondary Structure Formation

Main-chain chiral poly(2-oxazoline)s: Influence of alkyl side-chain on secondary structure formation in solution

2011 ◽  
Vol 49 (13) ◽  
pp. 2790-2801 ◽  
Author(s):  
Meta M. Bloksma ◽  
Sarah Rogers ◽  
Ulrich S. Schubert ◽  
Richard Hoogenboom
Keyword(s):  
Secondary Structure ◽  
Structure Formation ◽  
Main Chain ◽  
Side Chain ◽  
Alkyl Side Chain ◽  
Secondary Structure Formation

The influence of nitrous bases interactions on the DNA secondary structure formation

1975 ◽  
Vol 55 (2) ◽  
pp. 491-503 ◽  
Author(s):  
R.V. Polozov ◽  
V.I. Poltev ◽  
B.I. Sukhorukov
Keyword(s):  
Secondary Structure ◽  
Structure Formation ◽  
Dna Secondary Structure ◽  
Secondary Structure Formation
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