Intracellular signaling in proto-eukaryotes evolves to alleviate regulatory conflicts of endosymbiosis

The complex eukaryotic cell resulted from a merger between simpler prokaryotic cells, yet the relative timing and the role of the mitochondrial endosymbiosis with respect to other eukaryotic innovations has remained under dispute. Although expansion of the regulatory repertoire has been inferred from phylogenetic studies, gene regulation has not been taken into account in current scenarios of the mitochondrial endosymbiosis which mostly focus on the complementary energetic and ecological perspectives. The endosymbiotic state introduced several unique challenges to cells such as coordination of host and symbiont cell cycles and its disruption by leaking gene products and DNA fragments between host and symbionts. To investigate how these unique challenges impacted genome and network evolution during eukaryogenesis, we study a constructive computational model where two simple cells are forced into an obligate endosymbiosis. Across multiple in silico evolutionary replicates, we observe the emergence of different mechanisms for the coordination of host and symbiont cell cycles, stabilizing the endosymbiotic relationship. The most commonly evolved mechanism, implicit control, works without signaling between host and symbiont. Signaling only evolves under the influence of leaking gene products, while such regulatory interference is inherently harmful. In the fittest evolutionary replicate, the host controls the symbiont cell cycle entirely through signaling, mimicking the regulatory dominance of the nucleus over the mitochondrion that evolved during eukaryogenesis.