Biomathematical model of prebiotic autocatalytic RNA networks shows birth of adaptive immunity from degenerating molecular parasite catalysts
Authors: Pirovino Magnus , Iseli Christian , Curran Joseph A. , Conrad Bernard 
Published: May 2023

Catalysis and specifically autocatalysis are the quintessential building blocks of life. However, autocatalytic networks are necessary but not sufficient for life-like properties such as self-propagation and adaptation to emerge. We previously showed using Lotka-Volterra equations that a tripartite, early life cycle comprising a host-template, molecular parasites and hyperparasites (parasites of parasites) conferred superior stability to the habitat. Here we build on this model, and on the seminal notion that chemical networks and ecologically interacting biological species are akin, implying an instructive equational analogy between catalysis and ecology, both accurately modelled by equations from the Lotka-Volterra family. Template-based autocatalytic RNA networks seed the spontaneous emergence of immunity against molecular parasites, with degenerating molecular parasite catalysts being the founding seed of the homeostatic process. First, upon molecular parasite encounter, specific ribocatalysts 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, memorizing parasite-specific catalyst-subunits that now once more provide parasite resistance, in a homeostatically stabilized habitat. Third, under continuous exposure to progressively elaborate parasite populations, hyperparasite catalysts degenerate and embody antiparasite immunity. The observed triggering of microbial immunity by hyperparasitic microbial 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.Author SummaryThe quintessential components of life comprise a potent acceleration of naturally occurring, but improbable chemical reactions (catalysis), and the arrangement of accelerated chemical reactions in closed loops (autocatalytic sets). This is required, but is not sufficient for such networks to self-propagate and adapt. We previously developed an early life model for a stabilized habitat of networks, using a family of equations shown to accurately model both chemical reactions and the interactions of biological species. This model became stabilized only if the molecular host species was parasitized, an event considered unavoidable, and at the same time, the parasite itself was also parasitized. We now built on that model, using the same family of equations, by letting individual autocatalytic sets interact. The new results show that primitive autocatalytic networks emerge spontaneously, but inefficiently and resist parasites. With time, they become more efficient, which renders them parasite-sensitive. Upon continuous external parasite invasion, the primitive, parasite-resistant catalysts (hyperparasites) that still persist are recruited, conferring stability to the habitat. If the habitat is further overwhelmed with parasites, it selects the elegant solution of letting the parasite-resistant catalysts degenerate, which now produces immunity to those parasites (“antibodies”). This represents the birth of adaptive immunity.