Early Systems Biology and Prebiotic Networks

Systems Biology constitutes tools and approaches aimed at deciphering complex biological entities. It is assumed that such complexity arose gradually, beginning from a few relatively simple molecules at life’s inception, and culminating with the emergence of composite multicellular organisms billions of years later. The main point of the present paper is that very early in the evolution of life, molecular ensembles with high complexity may have arisen, which are best described and analyzed by the tools of Systems Biology. We show that modeled prebiotic mutually catalytic pathways have network attributes similar to those of present-day living cells. This includes network motifs and robustness attributes. We point out that early networks are weighted (graded), but that using a cutoff formalism one may probe their degree distribution and show that it approximate that of a random network. A question is then posed regarding the potential evolutionary mechanisms that may have led to the emergence of scale-free networks in modern cells. 1 Prebiotic Molecular Networks Most researchers admit that somewhere along the line towards the appearance of selfreproducing protocells, a web of interacting molecules must have been at work. Yet, investigators are divided on a crucial question related to the first reproducing entities. One set of scenarios claims that life began with a single molecular replicator, e.g. an RNA-like biopolymer [1-3]. It is further assumed that complex molecular networks came much later, and were genetically instructed by the replicating polymers. The second set of scenarios asserts that early replicating entities must have constituted complex molecular networks right from the outset. The latter view claims that the emergence of single molecules, whose inner works allowed them to instruct the synthesis of their own copies, are extremely unlikely under prebiotic conditions. It is claimed that the spontaneous accretion of specific mixtures or assemblies of simple organic molecules, capable of self-reproduction, is more probable. Furthermore, it is suggested that the capacity of such molecular assemblies to undergo a replication or reproduction-like process is a direct consequence of certain network properties parallel to those that allow present-day cells to divide and beget progeny. If the “networkfirst” scenario is right, then a better understanding of network properties within contemporary living cells should be a crucial tool for understanding prebiotic evolution. * These authors contributed equally to this article.