The Animal-fungi Hybrid Cell Cycle of the Zoosporic Fungus Spizellomyces punctatus - a New Model to Understand Evolution of Eukaryotic Cell Cycle Control

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2019

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Abstract

The cell cycle is arguably one of the most conserved regulatory networks within Eukaryotes. Despite the animals and fungi are sibling “kingdoms” within the Opisthokont supergroup, the core transcription factors that control commitment to cell division (E2F and SBF, respectively) and their repressors (Rb and Whi5, respectively) do not appear to have a shared molecular origin. My thesis work has focused on understanding how the networks that regulate cell cycle decisions have changed and rewired through evolutionary time.

By using comparative genomics, I found that the main fungal regulator (SBF) was acquired very early in the evolution of fungi by horizontal gene transfer from a viral origin. I also showed that this viral-derived transcription factor still coexists with the ancestral E2F in the zooporic fungus Spizellomyces punctatus, forming a hybrid cell cycle control network. I hypothesize a viral-derived regulator (SBF) hijacked cell cycle control in the dawn of Fungi by binding the promoters regulated by the ancestral counterpart (E2F), pushing cells to proliferation. This requires the invading SBF to be able to bind regulatory regions controlled by E2F. Using a high-throughput analyses of the DNA-binding properties of the SBF and E2F-family across Eukaryotic lineages I found that E2F and SBF share binding preferences, but that these are not completely overlapping, which could permit the evolutionary conservation of the hybrid E2F/SBF network in Spizellomyces. I then proceeded to test the potential differences \textit{in vivo} in accessibility to E2F and SBF binding sites by coupling in vitro DNA-binding information with nucleosomal and TF-footprints generated from MNase-seq data.

Finally, I developed Agrobacterium-mediated transformation in Spizellomyces, allowing me to describe basic characteristics of its developmental program using live-cell and fluorescence microscopy. By following nuclear dynamics with a fluorescently tagged histone I found that mitosis only initiates after germination, and that nuclei divide synchronously during sporogenesis. Furthermore, by following actin dynamics with LifeAct I showed that zoospores use actin-filled pseudopods to crawl, much like amoeba or animal cells, and that sporangia rely on complex actin dynamics during the formation of zoospores that are reminiscent of animal cellularization processes. This work highlights the importance of non-model systems for finding new solutions to longstanding questions in biology. This is a first step towards establishing Spizellomyces as a model system to study the evolution of key animal and fungal traits, particularly cell cycle regulation and development.

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Medina Tovar, Edgar Mauricio (2019). The Animal-fungi Hybrid Cell Cycle of the Zoosporic Fungus Spizellomyces punctatus - a New Model to Understand Evolution of Eukaryotic Cell Cycle Control. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/19852.

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