The fidelity of template-directed oligonucleotide ligation and its relevance to DNA computation

James, Kenneth D.; Boles, Amy R.; Henckel, Dorothy; Ellington, Andrew D.

doi:10.1093/nar/26.22.5203

Cited by 46 publications

(34 citation statements)

References 16 publications

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“…A related nonenzymatic replication scheme involves synthesis by the ligation of short 3 0 ,5 0 -linked oligomers (James and Ellington 1999). This is certainly an attractive possibility, made more plausible by the discovery of analogous ribozyme-catalyzed reactions (Bartel and Szostak 1993), but it faces two major obstacles.…”

Section: Nonenzymatic Replication Of Rnamentioning

confidence: 99%

The Origins of the RNA World

Robertson¹,

Joyce²

2010

Cold Spring Harbor Perspectives in Biology

447

326

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SUMMARYThe general notion of an "RNA World" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA-and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this "RNA-first" view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA.

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Section: Nonenzymatic Replication Of Rnamentioning

confidence: 99%

The Origins of the RNA World

Robertson¹,

Joyce²

2010

Cold Spring Harbor Perspectives in Biology

447

326

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“…After the discovery of a catalytic RNA (ribozyme) in 1982 (Kruger et al 1982), a number of experiments were aimed toward creating an RNA world in the laboratory (Bartel and Szostak 1993;Johnston et al 2001; for reviews see Szostak et al 2001;Müller 2006). The central molecule in such a system would be a ribozyme that replicates RNA polymers by polymerizing chemically activated units in a template-dependent fashion (James and Ellington 1999). A polymerase ribozyme was developed in 2001 that is able to recognize a primer/template duplex in trans and extend the primer 39 terminus using nucleoside triphosphates (Johnston et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Müller

Bartel²

2008

RNA

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During an early step in the evolution of life, RNA served both as genome and as catalyst, according to the RNA world hypothesis. For self-replication, the RNA organisms must have contained an RNA that catalyzes RNA polymerization. As a first step toward recapitulating an RNA world in the laboratory, a polymerase ribozyme was generated previously by in vitro evolution and design. However, the efficiency of this ribozyme is about 100-fold too low for self-replication because of a low affinity of the ribozyme to its primer/template substrate. To improve the substrate interactions by colocalizing ribozyme and substrate on micelles, we attached hydrophobic anchors to both RNAs. We show here that the hydrophobic anchors led to aggregates with the expected size of the corresponding micelles. The micelle formation increased the polymerization yield of full-length products by 3-to 20-fold, depending on substrates and reaction conditions. With the best-characterized substrate, the improvement in polymerization efficiency was primarily due to reduced sequence-specific stalling on partially extended substrates. We discuss how, during the origin of life, micellar ribozyme aggregates could have acted as precursors to membraneencapsulated life forms.

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“…While the templateinduced synthesis of oligonucleotides from smaller oligonucleotide precursors was successfully demonstrated in the laboratory [56,57,44,58], it seems impossible to replicate longer sequences without an enzyme [37]. Approaches to engineering a ribozyme-replicase have been very promising [23,25,38]. These experiments show that self-replication is most likely within the catalytic repertoire of nucleic acids [34].…”

Section: Introductionmentioning

confidence: 99%

Evolving towards the hypercycle: A spatial model of molecular evolution

Attolini

Stadler

2006

Physica D: Nonlinear Phenomena

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We extend earlier cellular automata models of spatially extended hypercycles by including an explicit genetic component into the model. This allows us to study the sequence evolution of hypercyclically coupled molecular replicators in addition to considering their population dynamics and spatial organization. In line with previous models, that considered either spatial organization or sequence evolution alone, we find both temporal oscillations of the relative concentration of the species forming the hypercycles as well as the formation of spatial organisations including spiral waves. We also confirm the greatly increased robustness of the spatially extended hypercycle against various classes of parasites.We find the sequence evolution of each of the hypercyclically coupled populations proceeds (after an inital selection-dominated phase) in a drift-like manner that can be described by a diffusion process in sequence space. Kimura's theory of neutral evolution is therefore applicable on long time-scales despite the fact that the hypercycle exhibits extreme periodic changes in population sizes and that are governed solely by frequency-dependent selection.

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The fidelity of template-directed oligonucleotide ligation and its relevance to DNA computation

Cited by 46 publications

References 16 publications

The Origins of the RNA World

The Origins of the RNA World

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Evolving towards the hypercycle: A spatial model of molecular evolution

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