  The emergence of replicases that can replicate themselves is a central issue
in the origin of life. Recent experiments suggest that such replicases can be
realized if an RNA polymerase ribozyme is divided into fragments short enough
to be replicable by the ribozyme and if these fragments self-assemble into a
functional ribozyme. However, the continued self-replication of such replicases
requires that the production of every essential fragment be balanced and
sustained. Here, we use mathematical modeling to investigate whether and under
what conditions fragmented replicases achieve continued self-replication. We
first show that under a simple batch condition, the replicases fail to display
continued self-replication owing to positive feedback inherent in these
replicases. This positive feedback inevitably biases replication toward a
subset of fragments, so that the replicases eventually fail to sustain the
production of all essential fragments. We then show that this inherent
instability can be resolved by small rates of random content exchange between
loose compartments (i.e., horizontal transfer). In this case, the balanced
production of all fragments is achieved through negative frequency-dependent
selection operating in the population dynamics of compartments. This selection
mechanism arises from an interaction mediated by horizontal transfer between
intracellular and intercellular symmetry breaking. The horizontal transfer also
ensures the presence of all essential fragments in each compartment, sustaining
self-replication. Taken together, our results underline compartmentalization
and horizontal transfer in the origin of the first self-replicating replicases.
