The cell division cycle (CDC) cyclin family consists of several sub-families with a well-characterized cyclin box: (1) CycA (H. sapiens, A. thaliana), (2) CycB and CLB (H. sapiens, A. thaliana, S. cerevisiae, S. pombe), (3) CycD (H. sapiens, A. thaliana), (4) CycE (H. sapiens), and (5) CLN (S. cerevisiae, S. pombe). We combined CycA, CycB, CycD, CycE, CLB, and CLN sequences from H. sapiens (10 cyclins), A. thaliana (13 cyclins), S. cerevisiae (9 cyclins), and S. pombe (5 cyclins) to create a eukaryotic CDC cyclin profile-HMM (pCYC.hmm) following the procedure outlined in the Methods. Our HMM profile was sensitive enough to discover known, but uncharacterized cyclin sub-families (CycO, CycF, CycG, CycI, CycJ, CycSDS) as bona fide CDC cyclins. A domain threshold of E-20 was used to identify potential CDC cyclin homologs. We first made a phylogeny of all cyclins to classify them. This dataset was then manually pruned to remove long-branches and problematic lineages. Our reduced CDC cyclin dataset (Figure 2—source data 1) has a total of 499 sequences. Columns with the top 10% Zorro score (496 positions) were used in our alignment. Confidence at nodes was assessed with multiple support metrics using different phylogenetic programs under LG model of evolution (aBayes and SH-aLRT metrics with PhyML, RBS with RAxML, Bayesian Posterior Probability with Phylobayes (23,163 sampled trees, meandiff= 0.01, maxdiff= 0.5)). Colored dots in branches indicate corresponding branch supports. Thick branches indicate significant support by at least two metrics, one parametric and one non-parametric; branch support thresholds are shown in the center of the figure; see Materials and methods.