Figure 6. Evolution of the N-terminal regulatory region of the B-type cyclins.

(A) Budding yeast have six B-type cyclins (Clb1–6), and their evolution can be traced through 3 duplication events to a single ancestor (Byrne and Wolfe, 2005; Gunbin et al., 2011). The common ancestor duplicated to produce Clb3/4 and Clb1/2/5/6, a tandem duplication led to the creation of Clb1/2 and Clb5/6 (Clb1/2 and Clb5/6 are still found adjacent to each other in the budding yeast genome), and finally a whole genome duplication produced the six Clbs seen today. The last common Clb ancestor, like all B-type cyclins, had a single D box and was likely destroyed in metaphase (Yamano et al., 1996; Gunbin et al., 2011). The Clb3/4 lineage retained this motif conformation. After the Clb1/2/5/6 duplication, Clb1/2 gained a KEN box and Clb5/6 gained an ABBA motif. Subsequently, after the Clb5/6 duplication, Clb6 lost both the D box and ABBA motif and gained a degron for a different ubiquitin ligase, SCF^Cdc4 (Amon et al., 1994; Hendrickson et al., 2001; Thornton and Toczyski, 2003; Jackson et al., 2006; Lu et al., 2014). Several of the Clbs also contain uncharacterized yet conserved non-canonical KEN boxes (DEN, NEN). The distinct motif content of the intrinsically disordered regulatory N-terminal regions of the Clb family is the major determinant of their ordered degradation. (B) Metazoan Cyclin A has acquired an ABBA motif independently of the fungal Clb5 ABBA motif acquisition.