title: Evolution of eukaryotic cell cycle regulation: stepwise addition of regulatory kinases and late advent of the CDKs.
abstract: Protein kinases regulate a number of critical events in mitosis and meiosis. A study of the evolution of kinases involved in cell cycle control (CCC) might shed light on the evolution of the eukaryotic cell cycle. In particular, applying quantitative phylogenetic methods to key CCC kinases could provide information on the relative timing of gene duplication events. To investigate the evolution of CCC kinases, we constructed phylogenetic trees for the CDC28 family and performed statistical tests of the tree topology. This family includes the cyclin-dependent kinases (CDKs), which are key regulators of the eukaryotic cell cycle, as well as other CCC kinases. We found that CDKs and, in particular, the principal cell cycle regulator Cdc28p, branch off the phylogenetic tree at a late stage, after several other kinases involved in either mitosis or meiosis regulation. On the basis of this tree topology, it is proposed that, at early stages of evolution, the eukaryotic cell cycle was not controlled by CDKs and that only a subset of extant kinases, notably the DNA damage checkpoint kinase Chk1p, were in place. During subsequent evolution, a series of duplications of kinase genes occurred, gradually adding more kinases to the CCC system, the CDKs being among the last major additions.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 20894, Bethesda, MD, USA.
authors.forename: Dmitri M
authors.initials: DM
authors.lastname: Krylov
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D000818:Animals; D005075:Biological Evolution; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology*; D020440:Gene Duplication; D006801:Humans; D008540:Meiosis / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases