Re-creating an RNA world

Abstract

The RNA world hypothesis states that life originated via a system based on RNA genomes and RNA catalysts. Researchers have been trying to develop such a system since catalytic RNAs (ribozymes) were discovered in 1982. This review summarizes the recent progress made in that endeavor and outlines the obstacles that remain to be overcome. After giving a short background on prebiotic chemistry and in vitro evolution, the discussion focuses on the generation of three important components of an RNA world: a sufficient polymerase ribozyme, self-replicating membrane compartments and ribozymes that are capable of performing basic metabolic processes.

Kinetic Models of the Prebiotic Replication of dsRNA under Thermal Cycling Conditions

“…Although it remains controversial if RNA or related macromolecules were "first," RNA synthesis would certainly have been a key bridge from abiotic chemistry to the biotic world (Orgel, 2004;Taylor, 2005;Müller, 2006;Ferris & Delano, 2008;Robertson & Joyce, 2010;Cheng & Unrau, 2010;Benner, Kim, & Yang, 2010). Models of RNA replication play an important role in inspiring experiments that would provide evidence for the RNA World.…”

“…In either of these cases, demonstrating non-enzymatic routes to the replication of dsRNA or related macromolecules is necessary to understand the synthesis of sufficient copies of this molecule to express molecular function, such as the catalytic activity of ribozymes. The copying mechanism would inevitably generate mutations that would lead to selection of advantageous sequences (Müller, 2006;Cheng & Unrau, 2010;Benner, Kim, & Yang, 2010). Thus, a replicating mechanism for RNA would be important for providing the macromolecules needed to initiate life.…”

The origin of modern terrestrial life

“…However, compelling theoretical and experimental arguments suggest that cell formation occurred early in life evolution [see for instance (de Duve, 2003;Deamer et al, 2006) (Muller, 2006) (Lopez-Garcia et al, 2006;Forterre, 2005)]. The formation of "protocells" was probably essential for the evolution of RNA replicators (see below) and the establishment of any sustained energy-driven protometabolism by (i) keeping together RNA replicators and their corresponding genomic RNAs (i.e., only catalysts enclosed by membranes can benefit from their own reaction), (ii) excluding potentially competing external parasitic RNAs, and (iii) preventing the dilution of molecules and macromolecules.…”

“…The formation of "protocells" was probably essential for the evolution of RNA replicators (see below) and the establishment of any sustained energy-driven protometabolism by (i) keeping together RNA replicators and their corresponding genomic RNAs (i.e., only catalysts enclosed by membranes can benefit from their own reaction), (ii) excluding potentially competing external parasitic RNAs, and (iii) preventing the dilution of molecules and macromolecules. Furthermore, a protometabolism able to synthesize nucleotides for RNA production would have also been able to produce simple (amphiphilic) molecules that are rather easy to synthesize prebiotically and could have been abundant on early Earth [see (Muller, 2006) and references therein]. Lipid vesicles can be produced quite easily in vitro from fatty acids or even better from fatty acid glycerol ester.…”

“…has not yet been experimentally demonstrated for their origin [for recent reviews, see (Joyce, 2002;Muller, 2006;Orgel, 2004) and references therein]. The main problem is the formation of ribose and nucleosides.…”