How is the single mitotic division elaborated to a double meiotic division?

It is our view that the mitotic cell division program is ancestral and that meiosis (sexual differentiation) evolved from mitotic cell division. If this is true, then studying the differences between the control networks of the relatively simple single mitotic division, and those that enable the more complex, double meiotic divisions should provide fundamental insights into the evolution of complexity.

Our previous research compared the biochemical activities of the Cyclin-dependent kinase Cdk1 and the related kinase Ime2. Cdk1 and Ime2 can phosphorylate the same targets on distinct sites and give the same output control. However, Cdk1-dependent phosphates can be removed by the phosphatase Cdc14, while Ime2-dependent phosphates cannot. This distinct recognition by phosphatases has been useful in the evolution of the double meiotic division because it enables the uncoupling of the DNA replication and spindle replication cycles (see Mol. Cell 2007).

We will build on these studies by further defining the biochemical specificities and in vivo targets of Ime2 and related kinases such as Cdc5. We will use a combination of chemical genetics with quantitative high-throughput mass spectrometry (see Science 2009) to better define kinase and phosphatase targets in vivo. We will use reconstitution of regulation in vitro and perturbations in vivo to understand the importance of phosphoregulation events, with a particular emphaisis on events that are coregulated by Ime2 and Cdk1.