Collaborative Research: Impact of a novel retrotransposon expansion on centromere function

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Centromeres are DNA regions that ensure the correct separation of chromosomes during a cell's reproduction, and are fundamental to genome evolution. However, due to the highly repetitive nature of DNA present in centromeres, further studies in identifying the make-up of this portion of DNA have been limited. In response to the roadblocks caused by the limited amount of research in this area, this project aims to advance our knowledge of centromere biology and evolution. This research will support outreach activities focused on the biology of gibbons, a critically endangered group of primates. As the main threats for these species are from human activities, a large part of the outreach effort for this work seeks to increase awareness of the precarious state of this species. Current conservation efforts, encompassing different venues, include informal seminars to the public and collaborations with primate centers and museums. In addition, this project will promote education through training of postdoctoral fellows, graduate students, undergraduate and local high school programs by providing experiential learning and exposure to modern technologies and training workshops.While expansions of DNA within centromeres are known for many species, most centromeres are stable over evolutionary time and relatively uniform across all centromeres in one genome. Decoupling equilibration events across chromosomes from the initial seeding events specific to a subset of chromosomes has not been possible in most model systems. This project capitalizes on the recently discovered centromeric expansion of a selfish element, the LAVA retroelement, in a subset of chromosomes in one gibbon genus (Hoolock). This project will build upon foundational discoveries in gibbon centromeres, the newly released gibbon genome sequence and novel genomics approaches for studying complex, repeat-rich regions. This project will test the hypothesis that both LAVA and neighboring satellite DNA bind inner kinetochore proteins, implicating genetic conflict in the seeding and expansion at centromeres. Second, based on observations that the Hoolock centromere structure is similar to that found in marsupials and plants, this project will include analyses of transcripts from centromeric repeats to determine whether transcription from centromere retroelements is associated with young centromere restructuring or with subsequent stabilization. Finally, this research will incorporate emerging next-generation sequencing technologies to assemble Hoolock centromeres from single chromosomes. Collectively, these aims will determine the impact of the organization and function of repeats among newly seeded centromeres and stabilized centromeres within one karyotype.This project is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.