Malik, Harmit SRoach, Kevin2013-04-172013-10-152013-04-172012Roach_washington_0250E_11290.pdfhttp://hdl.handle.net/1773/22451Thesis (Ph.D.)--University of Washington, 2012Centromeres and the kinetochore proteins that bind them are required for chromosome segregation during every eukaryotic cell division. Despite this conserved function, ongoing conflict between selfish centromeric DNA and the proteins of the kinetochore causes both to rapidly evolve. Centromeres (centromeric DNA satellite arrays) are able to gain evolutionary advantages by driving during asymmetric female meiosis, in turn conferring a selective advantage to kinetochore proteins that can suppress centromeric imbalances. For example, the centromeric variant of histone H3 (CenH3), the basis of kinetochore function and the epigenetic mark of active centromeres, is rapidly evolving across many taxa, including primates. While conflict with driving centromeres can explain the rapid evolution of CenH3, it cannot explain incongruent patterns of functional complementation and localization. I show that that the co-evolutionary constraints of chaperone interaction drive these divergent patterns of CenH3 functional divergence. The presence or absence of a conserved centromeric histone chaperone, SCM3/HJURP, in the genome is able to fully predict the differences in functional complementation and localization of CenH3. I expand previous evolutionary analyses using genomic sequence data and evolutionary analysis to explore how the entire primate kinetochore is shaped by conflict with centromeres. I find that the primate inner kinetochore is defined by rapid evolution, while the outer kinetochore and fibrous corona are undergoing purifying selection. Furthermore, I find that the CenH3 chaperone HJURP is also evolving under positive selection. The extensive adaptive evolution of the primate kinetochore provides new evidence of the breath of the conflict between centromere and kinetochore, as well as new targets to investigate the functional consequences of genetic conflict on cell division and kinetochore localization.application/pdfen-USCopyright is held by the individual authors.Centromere; Evolution; Histone; KinetochoreGeneticsEvolution & developmentCellular biologygeneticsThesis