scholarly journals Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

2017 ◽  
Vol 4 (9) ◽  
pp. 170376
Author(s):  
Nisha Dhar ◽  
Marc S. Weinberg ◽  
Richard E. Michod ◽  
Pierre M. Durand

In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3′ end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life.

Author(s):  
Steven E. Vigdor

Chapter 7 describes the fundamental role of randomness in quantum mechanics, in generating the first biomolecules, and in biological evolution. Experiments testing the Einstein–Podolsky–Rosen paradox have demonstrated, via Bell’s inequalities, that no local hidden variable theory can provide a viable alternative to quantum mechanics, with its fundamental randomness built in. Randomness presumably plays an equally important role in the chemical assembly of a wide array of polymer molecules to be sampled for their ability to store genetic information and self-replicate, fueling the sort of abiogenesis assumed in the RNA world hypothesis of life’s beginnings. Evidence for random mutations in biological evolution, microevolution of both bacteria and antibodies and macroevolution of the species, is briefly reviewed. The importance of natural selection in guiding the adaptation of species to changing environments is emphasized. A speculative role of cosmological natural selection for black-hole fecundity in the evolution of universes is discussed.


2019 ◽  
Vol 47 (13) ◽  
pp. 6569-6577 ◽  
Author(s):  
Christine He ◽  
Adriana Lozoya-Colinas ◽  
Isaac Gállego ◽  
Martha A Grover ◽  
Nicholas V Hud

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.


2016 ◽  
Vol 25 (2) ◽  
pp. 231-245 ◽  
Author(s):  
Natalia Szostak ◽  
Szymon Wasik ◽  
Jacek Blazewicz

According to some hypotheses, from a statistical perspective the origin of life seems to be a highly improbable event. Although there is no rigid definition of life itself, life as it is, is a fact. One of the most recognized hypotheses for the origins of life is the RNA world hypothesis. Laboratory experiments have been conducted to prove some assumptions of the RNA world hypothesis. However, despite some success in the ‘wet-lab’, we are still far from a complete explanation. Bioinformatics, supported by biomathematics, appears to provide the perfect tools to model and test various scenarios of the origins of life where wet-lab experiments cannot reflect the true complexity of the problem. Bioinformatics simulations of early pre-living systems may give us clues to the mechanisms of evolution. Whether or not this approach succeeds is still an open question. However, it seems likely that linking efforts and knowledge from the various fields of science into a holistic bioinformatics perspective offers the opportunity to come one step closer to a solution to the question of the origin of life, which is one of the greatest mysteries of humankind. This paper illustrates some recent advancements in this area and points out possible directions for further research.


2015 ◽  
Vol 87 (2) ◽  
pp. 205-218 ◽  
Author(s):  
Albert C. Fahrenbach

AbstractThe nonenzymatic synthesis of nucleic acids, in particular, RNA, and the template-directed synthesis of artificial organic molecules, such as macrocycles, catenanes and rotaxanes, have both undergone significant development since the last half of the 20th century. The intersection of these two fields affords insights into how template effects can lead to information copying and storage at the molecular level. Mechanistic examples of model template-directed RNA replication experiments as well as those for totally artificial organic template-directed syntheses will be discussed. The fact that templates typically bind to their reacted products more tightly than their unreacted substrates may be a mechanistic feature necessary to store information in the form of nucleic acids. Understanding the mechanisms of nonenzymatic RNA synthesis is not only essential for testing the RNA world hypothesis in the context of the origin of life on Earth and other planetary bodies, but may one day afford chemists the insights to construct their own artificial molecular replicators.


Author(s):  
Kenji Ikehara

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.


Elements ◽  
2017 ◽  
Vol 13 (4) ◽  
pp. 261-265 ◽  
Author(s):  
Yoshihiro Furukawa ◽  
Takeshi Kakegawa

According to the RNA World hypothesis, ribonucleic acid (RNA) played a critical role in the origin of life. However, ribose, an essential component of RNA, is easily degraded: finding a way to stabilize it is critical to the viability of the hypothesis. Borate has been experimentally shown to have a strong affinity for ribose, and, thus, could have protected ribose from degradation in the formose reaction, a potential process for prebiotic ribose formation. Accumulation of borate on Hadean Earth (prior to ~4,000 Ma) might have been a key step in the chemical evolution of the biotic sugar. Proto-arcs are suggested as a geological setting sufficiently rich in borate to stabilize ribose during the Hadean.


2004 ◽  
Vol 213 ◽  
pp. 321-324 ◽  
Author(s):  
Laura Guogas ◽  
James Hogle ◽  
Lee Gehrke

Central to understanding the origin of life is the elucidation of the first replication mechanism. The RNA World hypothesis suggests that the first self-replicating molecules were RNAs and that DNA later superceded RNA as the genetic material. RNA viruses were not subjected to the same evolutionary pressures as cellular organisms; consequently, they likely possess remnants of earlier replication strategies. Our laboratory investigates how members of the RNA virus family Bromoviridae can have structurally distinct 3' end tags yet are specifically recognized by conserved replication enzymes. This work addresses the idea that 3' tRNA tails were functionally replaced in some viruses by an RNA-protein complex. These viruses may serve as a timeline for the transition from the RNA world to DNA and protein based life.


2005 ◽  
Vol 2 (6) ◽  
pp. 1719-1737 ◽  
Author(s):  
A. V. Vlassov

Abstract. The RNA World hypothesis states that the present-day life, which is based on DNA genomes and protein enzymes, was preceded by a simpler life form based primarily on RNA. During this era, the genetic information resided in the sequence of RNA molecules and the phenotype derived from the catalytic properties of RNA. Though it is a widely accepted scenario, a number of problems remain unsolved. One of the biggest questions is how complex RNAs could evolve, survive and replicate under typically assumed ''warm and wet'' conditions, taking into account that the RNA phosphodiester backbone is chemically unstable under these conditions. We suggest that prebiotic conditions associated with freezing could have been of key importance in the early RNA World, and discuss the role of primitive catalytic RNA in the evolution of RNA size and complexity.


2006 ◽  
Vol 361 (1474) ◽  
pp. 1751-1760 ◽  
Author(s):  
William R Taylor

The RNA world hypothesis requires a ribozyme that was an RNA-directed RNA polymerase (ribopolymerase). If such a replicase makes a reverse complementary copy of any sequence (including itself), in a simple RNA world, there is no mechanism to prevent self-hybridization. It is proposed that this can be avoided through the synthesis of a parallel complementary copy. The logical consequences of this are pursued and developed in a computer simulation, where the behaviour of the parallel copy is compared to the conventional reverse complementary copy. It is found that the parallel copy is more efficient at higher temperatures (up to 90°C). A model for the ribopolymerase, based on the core of the large subunit (LSU) of the ribosome, is described. The geometry of a potential active site for this ribopolymerase suggests that it contained a cavity (now occupied by the aminoacyl-tRNA) and that an amino acid binding in this might have ‘poisoned’ the ribopolymerase by cross-reacting with the nucleoside-triphosphate before polymerization could occur. Based on a similarity to the active site components of the class-I tRNA synthetase enzymes, it is proposed that the amino acid could become attached to the nascent RNA transcript producing a variety of aminoacylated tRNA-like products. Using base-pairing interactions, some of these molecules might cross-link two ribopolymerases, giving rise to a precursor of the modern ribosome. A hybrid dimer, half polymerase and half proto-ribosome, could account for mRNA translocation before the advent of protein elongation factors.


2021 ◽  
pp. 82-96
Author(s):  
Franklin M. Harold

The origin of life is the most consequential problem in biology, possibly in all of science, and it remains unsolved. This chapter summarizes what has been learned and highlights questions that remain open, including How, Where, When, and especially Why. LUCA, some four billion years ago, already featured the basic capacities of contemporary cells. These must have evolved still earlier, at a nebulous proto-cellular stage. There is good reason to believe that enzymes, DNA, ribosomes, electron-transport chains, and the rotary ATP synthase all predate LUCA and were shaped by the standard process of variation and natural selection, but we know next to nothing about how cells ever got started. I favor the proposal that it began with a purely chemical dynamic network capable of reproducing itself, that may have originated by chance. Natural selection would have favored the incorporation of any ancillary factors that promoted its kinetic stability, especially ones that improved reproduction or gave access to energy. All the specifics are in dispute, including the role of a prebiotic broth of organic chemicals, the nature and origin of enclosure, the RNA world, and a venue in submarine hydrothermal vents. My sense is that critical pieces of the puzzle remain to be discovered.


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