Nucleotide substrates arrive as Gaussian-distributed, randomly timed A and B substrate spikes (jagged arrows, middle, Fig. 1), undergo unguided chemical

polymerization (blue arrow), base-pairing (square of green arrows), and possibly replication (magenta arrow), with first-order decay of all molecules (gray-gradient arrows). The (green) loop at the bottom represents pairing and dissociation of the base-paired dimer (von Kiedrowski 1986), AB_BA (underscores symbolize base pairing), which is the replication product of self-complementary A and B. Colored arrows can be taken together to describe other reaction logic: for example, reliable, constant STAT inhibitor supplies of A and B, which stable synthesis is later contrasted with the sporadically fed pool (Yarus 2012). The Fig. 1 inset (upper right) describes a possible AB synthesis in more detail. Ψ is an activating group that allows polymerization, AZD1390 in vivo BLZ945 concentration as in the nucleotide phosphorimidazolide introduced by Orgel (Sawai and Orgel 1975), and shown to have a simple abiotic

synthesis by Lohrmann (Lohrmann 1977). Below the dotted line is a possible template (A and B are assumed to be complementary; (Yarus 2012)), to emphasize that AB synthesis can plausibly proceed via either untemplated (inset top only; (Kanavarioti et al. 1992)) or templated means (replication; inset top + bottom). The AB backbone is drawn 5′-5′ in emulation of cofactors like NAD, which are ancient (White 1976) and conceivably combine templating and chemical activities (Yarus 2011a). However, the chemical identity of AB is not crucial to conclusions here, though it can likely be identified by a Bayesian inquiry (Yarus et al. 2005) into the existence of crucial templating reactions. Net replication in a sporadically fed pool is explored in Fig. 2, which plots number of pools versus total AB output in 1,000 consecutive simulations run for 100 A or B lifetimes. Values employed for rates and equilibria are those of the “standard system” used previously

((Yarus RANTES 2012), Fig. 2), which was designed to emulate known RNA chemistry and be mildly replicating at 100 A or B lifetimes. The plot compares integrated direct synthesis (blue in Fig. 1), integrated templated AB synthesis (magenta) and the largest AB peak (black). Fig. 2 Numbers of 100-lifetime simulations with particular integrated AB output after 1000 total simulations of the sporadically fed pool. Blue is integrated direct AB synthesis (blue arrow in Fig. 1); magenta is integrated replication (templated synthesis; magenta arrow in Fig. 1), and black is the largest AB peak during a 100 lifetime pool simulation Pool histories that yield large and small AB synthesis (Fig. 2) are different in a suggestive way.