Origin of Self-Replicating Biopolymers: Autocatalytic Feedback Can Jump-Start the RNA World Meng Wu Æ Paul G. Higgs Received: 13 August 2009 / Accepted: 14 August 2009 / Published online: 24 September 2009 Ó Springer Science+Business Media, LLC 2009 Abstract Life is based on biopolymers that have the ability to replicate themselves. Here we consider how a self-replicating RNA system may have originated. We consider a reaction system in which polymerization is possible by the addition of an activated monomer to the end of a chain. We suppose that a small fraction of polymers longer than some minimum length L have the ability to act as polymerase ribozymes. Polymerization can occur spontaneously at a slow rate and can also be catalyzed by polymerase ribozymes, if these ribozymes exist. The sys- tem contains autocatalytic feedback: increasing the poly- merization rate causes the ribozyme concentration to increase, which causes the polymerization rate to further increase. For an infinite volume, the dynamics are deter- ministic. There are two stable states: a ‘dead’ state with a very low concentration of ribozymes and a polymerization rate almost equal to the spontaneous rate, and a ‘living’ state with a high concentration of ribozymes and a high rate of polymerization occurring via ribozyme catalysis. In a finite volume, such as the interior of a lipid vesicle or other small compartment, the reaction dynamics is stochastic and concentration fluctuations can occur. Using a stochastic simulation, we show that if a small number of ribozymes is initially formed spontaneously, this can be enough to drive the system from the dead to the living state where ribo- zyme-catalyzed synthesis of large numbers of additional ribozymes occurs. This transition occurs most easily in volumes of intermediate size. Keywords RNA world  Ribozyme  Autocatalysis  Feedback  Origin of life  Metabolism  Replication  Stochastic reaction dynamics Introduction Life as we know it relies on the existence of self-replicating sets of biopolymers. Modern cells use DNA, RNA, and proteins, with DNA acting principally for information storage and proteins acting principally as catalysts. How- ever, some much simpler system must have existed at the time of the origin of life. The RNA World hypothesis proposes that early organisms contained self-replicating systems in which RNA was both the informational polymer and the key catalytic molecule (Gilbert 1986; Bartel and Unrau 1999; Szostak et al. 2001; Joyce 2002; Orgel 2004). The translation mechanism provides the main evidence that RNA preceded proteins. The sequences of proteins are encoded in mRNAs; rRNAs are the main functional com- ponent of the ribosome, and tRNAs enable translation to occur via the codon–anticodon interactions that define the genetic code. Naturally occurring ribozymes are capable of a versatile range of catalytic functions (Doudna and Cech 2002). The most important one is ribosomal RNA, and along with several other types of RNAs are considered to be relics of the RNA world (Jeffares et al. 1998). Thus, in our opinion, the evidence that RNA-based life once existed and that RNA could have carried out the full range of required functions is persuasive. However, it is still not clear how the RNA world got started, and whether life actually began with self-replicat- ing RNAs. The chemistry that would have been required to initiate the RNA world is complex. First, prebiotic syn- thesis of individual RNA nucleotides is not easy (Joyce M. Wu  P. G. Higgs (&) Department of Physics and Astronomy, Origins Institute, McMaster University, Hamilton, ON L8S 4M1, Canada e-mail: higgsp@mcmaster.ca 123 J Mol Evol (2009) 69:541–554 DOI 10.1007/s00239-009-9276-8