title: Widespread Recurrent Patterns of Rapid Repeat Evolution in the Kinetochore Scaffold KNL1.
abstract: The outer kinetochore protein scaffold KNL1 is essential for error-free chromosome segregation during mitosis and meiosis. A critical feature of KNL1 is an array of repeats containing MELT-like motifs. When phosphorylated, these motifs form docking sites for the BUB1-BUB3 dimer that regulates chromosome biorientation and the spindle assembly checkpoint. KNL1 homologs are strikingly different in both the amount and sequence of repeats they harbor. We used sensitive repeat discovery and evolutionary reconstruction to show that the KNL1 repeat arrays have undergone extensive, often species-specific array reorganization through iterative cycles of higher order multiplication in conjunction with rapid sequence diversification. The number of repeats per array ranges from none in flowering plants up to approximately 35-40 in drosophilids. Remarkably, closely related drosophilid species have independently expanded specific repeats, indicating near complete array replacement after only approximately 25-40 Myr of evolution. We further show that repeat sequences were altered by the parallel emergence/loss of various short linear motifs, including phosphosites, which supplement the MELT-like motif, signifying modular repeat evolution. These observations point to widespread recurrent episodes of concerted KNL1 repeat evolution in all eukaryotic supergroups. We discuss our findings in the light of the conserved function of KNL1 repeats in localizing the BUB1-BUB3 dimer and its role in chromosome segregation.
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, The Netherlands Center for Molecular Medicine, University Medical Center Utrecht, The Netherlands Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, The Netherlands.
authors.forename: Eelco
authors.initials: E
authors.lastname: Tromer
authors.affiliation: Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, The Netherlands b.snel@uu.nl g.j.p.l.kops@umcutrecht.nl.
authors.forename: Berend
authors.initials: B
authors.lastname: Snel
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, The Netherlands Center for Molecular Medicine, University Medical Center Utrecht, The Netherlands Cancer Genomics Netherlands, University Medical Center Utrecht, The Netherlands b.snel@uu.nl g.j.p.l.kops@umcutrecht.nl.
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D018428:Drosophilidae / Q000235:genetics; D056890:Eukaryota; D019143:Evolution, Molecular; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics*; D010802:Phylogeny; D020449:Repetitive Sequences, Amino Acid; D014714:Vertebrates / Q000235:genetics
chemical_list: C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins
keywords: BUB1; KNL1; kinetochore; mitosis; repeat evolution