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Brauns, Fridtjof; Iñigo de la Cruz, Leila; Daalman, Werner K.-G.; de Bruin, Ilse; Halatek, Jacob; Laan, Liedewij; Frey, Erwin (2023): Redundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast. Nature Communications, 14 (1). ISSN 2041-1723

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How can a self-organized cellular function evolve, adapt to perturbations, and acquire new sub-functions? To make progress in answering these basic questions of evolutionary cell biology, we analyze, as a concrete example, the cell polarity machinery of Saccharomyces cerevisiae. This cellular module exhibits an intriguing resilience: it remains operational under genetic perturbations and recovers quickly and reproducibly from the deletion of one of its key components. Using a combination of modeling, conceptual theory, and experiments, we propose that multiple, redundant self-organization mechanisms coexist within the protein network underlying cell polarization and are responsible for the module’s resilience and adaptability. Based on our mechanistic understanding of polarity establishment, we hypothesize that scaffold proteins, by introducing new connections in the existing network, can increase the redundancy of mechanisms and thus increase the evolvability of other network components. Moreover, our work gives a perspective on how a complex, redundant cellular module might have evolved from a more rudimental ancestral form.

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