4)), thereby making the overall system one that replicates. There is also a small contribution to replication from 7 to 11 spike episodes, but this is less significant because, despite their similar size, they are less frequent (Figs. 4 and 5). Fig. 5 Total, templated and direct output from each type of episode in the 250 curated episodes. Black – total AB, Magenta – templated

AB, Blue – directly synthesized AB. Numbered arrows give ‘fold-replication’ Smad inhibitor for each episode class. Left ordinate – total output, summed. Right ordinate – fraction of total output, summed The ‘standard system’ was chosen to be one that replicated to a small degree, just ‘past the Darwinian boundary’, in order to investigate the onset of replication (Yarus 2012). If the mean replication of the curated system in Fig. 5 is calculated by summing the products (fraction output times the ratio of templated to direct synthesis) for all episodes,

a system composed of these curated episodes replicates 1.36-fold, in agreement with prior overall behavior of the standard pool (Yarus 2012). Thus the 250 curated episodes quantitatively account for the mean behavior of the standard sporadically fed pool integrated over 100 lifetimes, supporting this episodic analysis. These outcomes can be explained: replication is more complex than direct chemical synthesis of AB, because templated synthesis requires the prior synthesis of an AB template. Consider designing a reactor to produce AB – delivery this website of a spike of A and a spike

of B in either order suffices for direct chemical synthesis. However, to replicate in the reactor we must ideally make AB template and then supply unstable A and B again for templated synthesis. Therefore, the ideal sequence of substrate spikes for a replication reactor has ≥ 4 spikes. Importantly, the sporadically fed pool is a reactor that utilizes near-ideal reaction sequences for replication without outside instruction, relying only on random substrate arrival to recurrently replicate AB, and thereby recurrently test the potentialities of Darwinian change. This discussion can be made more concrete by comparing example episodes (all events significantly changing synthesis during the course of a single population of AB) from standard pool simulations. Figure 6a and b illustrate the kinetics for a typical 2-spike Liothyronine Sodium episode and a 5-spike episode, respectively, plotted over 15 A or B lifetimes. For clarity, only one of every 50 calculated kinetic points is shown. Fig. 6 Simple (a) and complex (b) synthetic episodes in a complete sporadically fed system; chosen for illustration a. Two substrate spikes coincidentally overlap. Light blue is substrate A; brown is substrate B (both on left axis); blue is direct AB synthesis; magenta is templated AB, black is total AB in all forms and from all sources (all AB on right axis). b Five substrate spikes coincidentally overlap during the history of one AB population.