volved in present day regulation of the eukaryotic U0126 FDA cell cycle was already present in this ancestral organism. Supporting this hypothesis, nearly all the proteins under study possessed conserved functional domains similar to those present in components that were experimentally proved to be part of the APC C or targeted by this ubiquitin ligase. This indicated that all the identified orthologues of APC C components and targets had similar molecular functions. Moreover, experimental data from plants and excavates have shown that most components identified by our analysis were part of or targeted by the APC C. This strongly suggested that they inher ited their function from the Inhibitors,Modulators,Libraries ancestral proteins present in LECA, and therefore that a nearly modern APC C and control of the cell cycle existed in LECA.

This also suggested that, in lineages for which no functional data were available, the orthologues that we have identified were likely involved in the control of the cell cycle and, therefore, may constitute interesting targets for experi mental work. Although the origin of most APC C components and targets could be traced back to LECA Inhibitors,Modulators,Libraries and most of them have been conserved throughout the evolution of eukar yotes, some component gains could also be observed. Most of them resulted from gene duplications of adap tors co activators that occurred independently in differ ent lineages. This was in agreement with recent reports of new, and often specific, activities of the APC C in some eukaryotes.

This suggested that most of the APC C evolution since LECA has Inhibitors,Modulators,Libraries concerned the acquisition of new regulatory functions by increasing the repertoire of adaptors co activators, even if we can not rule out the possibility that adaptors co activators present in single copies in some lineages were able to interact with a larger spectrum of targets than their multiple copies counterparts. In addition to the classical activators co activators, a recent interactomic study in A. thaliana suggested the presence of three novel APC C interactors specific to land plants that were not homologous to the Cdc20 Cdh1 family. However, although they inter acted with the APC C, their biological function has still not been established. Nevertheless, this supported that lineage specific innovations are expected to be discov ered when biological data on a broader diversity of eukaryotes becomes available.

In contrast, we also observed that convergent events of streamlining occurred secondarily Inhibitors,Modulators,Libraries Dacomitinib in various lineages, like Apicomplexa, G. lamblia and E. histolytica. The reasons explaining those massive loss events are unclear, though we could not discard that, at least for a number of cases, they might be linked to an extreme accelera tion of their evolutionary rate beyond detection. This hypothesis was supported by the high evolutionary rates exhibited by the few components still harboured by Api choose size complexa. However, the detection of APC C subunits and targets in fast evolving organisms, like E. cuni