An all RNA Hypercyclic Network

A hypercycle is a cooperative organization of autocatalytic units that are associated in a cyclic linkage in such a way that there is a mutual survival and regulated growth of all the units involved. Compared to non‐coupled self‐replicating units, which can only sustain a limited amount of genetic information, the hypercycle allows the maintenance of large amounts of information through cooperation among otherwise competitive units. As such, this reaction network may have played a significant role in precellular evolution during the origins of life on the Earth. However, hypercycles have never been empirically demonstrated in the absence of cell‐like compartmentalization. In the current work, hypercyclic behavior is demonstrated in the autocatalytic assembly of Azoarcus group I ribozyme. Three different constructs of the Azoarcus ribozyme with different internal guide sequences (IGS) – GUG (canonical), GAG, and GCG – are capable of a minimal amount of self‐assembly when broken into two fragments. Here, self‐assembly depends on a mismatch with non‐complementary sequences, CGU, CAU and CUU, respectively, to be recognized by IGS via autocatalysis. Yet when all three constructs are present in the same reaction vessel, concomitant assembly of all three is enhanced through an interdependent hypercyclic reaction network. Analysis of these reactions indicates that each system is capable of guiding its own reproduction weakly, along with providing enhanced catalytic support for the reproduction of one other construct system through matched IGS‐tag interactions. Also, when co‐incubated with non‐interacting (i.e., selfish) yet efficient self‐assembly systems, the hypercyclic assembly outcompetes the selfish self‐assembly systems, demonstrating the ability of a hypercyclic organization to possess an evolutionary advantage.