Biomathematical model of prebiotic autocatalytic RNA networks shows birth of adaptive immunity from degenerating molecular parasite catalysts

Abstract

Autocatalytic networks likely played a central role in the shift from inanimate systems to protocells. Using an established hyperparasite framework, we model the emergence of antiparasite immunity using the Lotka Volterra equations. It builds on autocatalytic, increasingly complexed RNA networks reflecting the historical exposure to ubiquitous molecular parasites. First, upon parasite encounter, specific catalysts providing parasite resistance appear in primordial autocatalytic cycles, supplanted by promiscuous, efficiently self-replicating, but parasite sensitive ribozymes. This is supported by catalyst tradeoff analysis. Substrate promiscuity confers high catalytic activity, but entails parasite exposure, higher substrate specificity implies relatively lower activity, yet it offers parasite resistance. Second, sustained parasite influx generates hyperparasite cycles, reactivating the original, parasite-specific catalyst-subunit that now once more provides parasite resistance, in a homeostatically stabilized habitat, empirically consistent with phage satellites and defective RNA viruses induced across a range of parasite loads. Third, under continuous exposure to progressively elaborate parasite populations, hyperparasites degenerate and embody antiparasite immunity. Again, the observed triggering of antiviral immunity by phage satellite encoded antiphage systems and defective RNA virus genomes are in agreement with this model. As such, it offers an attractive and unifying theory for the spontaneous birth of immunity in early life.

Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity

“…We previously developed a tripartite early-life host-parasite-hyperparasite framework based on Lotka Volterra (LV)-equations [31,59]. The present work arrives at similar results, showing that LVbased equations provide an adequate approximation for the more realistic, kinetics-based model developed here.…”