Adaptability and evolution of the cell polarization machinery in budding yeast

Abstract

SummaryHow 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 show 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 how 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 suggests how a complex, redundant cellular module could have evolved from a more rudimental ancestral form.

The Path towards Predicting Evolution as Illustrated in Yeast Cell Polarity

“…Concretely, in [22] a mutant strongly defective in polarity establishment was experimentally evolved and found to recover remarkably reproducibly, e.g., the first rescuing mutation to sweep the population was always the same. Because of this exhibited tractability of the adaptations, network structures within the polarity network that facilitated evolution could be concretely interpreted in terms of redundancies [23]. In another approach to determine the flexibility of the polarity network, historical evolution was studied for 40+ proteins in almost 300 fungal species in [11].…”

“…To illustrate this point, a bottom-up model was constructed in [26] where molecular details were coarse-grained following analysis on numerical simulations of multiple polarity mechanisms [23]. This approach was successful in quantitatively describing the fitness along the evolutionary trajectory in [22].…”

“…We present three case studies in our review to reflect different stages in this knowledge quest; while literature on the first case, bud scar proteins, has been quite advanced for several years, only recently the GAP mechanism [23] (second case) has been revealed and for Nrp1 (third case) more work remains. These cases illustrate how to move from detecting the strong and more obvious phenotypes to unveiling evolutionary important hidden features (such as for Nrp1).…”

“…This feedback is sufficient for polarity success, which becomes rather insensitive to GAP abundance. More details on the GAPs were uncovered in [23] and are placed in a broader context in the case study further on.…”

“…The latter is the least cross-linked of the two, providing a possible justification for referring to the WT mechanism as the Rdi1 polarity mechanism, as in [24]. Cla4 is more context-dependent, possibly having two opposing roles, promoting and inhibiting polarity [23,88,89]. Yet both Rdi1 and Cla4 are dispensable for polarity [88,90].…”