Evolution of cell cycle control: same molecular machines, different regulation.

Decades of research has together with the availability of whole genomes made it clear that many of the core components involved in the cell cycle are conserved across eukaryotes, both functionally and structurally. These proteins are organized in complexes and modules that are activated or deactivated at specific stages during the cell cycle through a wide variety of mechanisms including transcriptional regulation, phosphorylation, subcellular translocation and targeted degradation. In a series of integrative analyses of different genome-scale data sets, we have studied how these different layers of regulation together control the activity of cell cycle complexes and how this regulation has evolved. The results show surprisingly poor conservation of both the transcriptional and the post-translation regulation of individual genes and proteins; however, the changes in one layer of regulation are often mirrored by changes in other layers, implying that independent layers of control coevolve. By taking a bird's eye view of the cell cycle, we demonstrate how the modular organization of cellular systems possesses a built-in flexibility, which allows evolution to find many different solutions for assembling the same molecular machines just in time for action.