Genetic Conflict Shapes Centromeres and Heterochromatin

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PROJECT SUMMARY Chromosome segregation is an essential process. The key chromosomal sites that ensure proper segregation of chromosomes are centromeres, which bind microtubules that pull chromosomes or chromatids apart during meiosis and mitosis. Centromere function is thus essential for chromosome segregation. Defective centromeres can lead to aneuploidy, infertility, and birth defects like Down’s syndrome. Despite the conservation of the chromosome segregation process, centromeric proteins like CenH3, which bind centromeric DNA to assemble microtubule-recruiting kinetochores, evolve rapidly between closely related species. Their rapid evolution is unexpected and could imperil the fidelity of the chromosome segregation process. We previously proposed that this rapid evolution occurs due to ‘centromere-drive’, i.e., competition between chromosomes during female meiosis, in which only one of four meiotic products is chosen to be the egg pronucleus. Using an approach that combines insights from evolutionary genetics and cell biology, and state-of-the-art genome engineering tools, we propose to test this model of genetic conflict in Drosophila species. Furthermore, based on our finding of recurrent duplication of CenH3 in Drosophila species, we will test whether somatic versus germline centromeric functions have different functional constraints, which are easiest to resolve via gene duplication and specialization of CenH3 genes.