Redundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast

Abstract

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.

The origin of septin ring size control in budding yeast

“…5i, j). Overall, given that the SBER model can explain several observed phenomena and that Cdc42 polarization is a remarkably robust process [Brauns et al, 2023], we argue that multiple mechanisms promote robust septin ring formation.…”

“…Overexpression of both Cdc42 and GEFs is fatal [Howel et al, 2012], and the deletion of GAP proteins reduces the replicative lifespan of yeast cells [Meitinger et al, 2014;Kang et al, 2022]. Even though Cdc42 polarization is remarkably robust [Brauns et al, 2023], there seems to be a need to maintain polarity protein balance. Interestingly, in computational models, an additional consequence of the increased amount of polarity proteins is that larger cells form multiple stable clusters [Borgqvist et al, 2021;Chiou et al, 2021], aligning with observations that in larger rsr1Δ cells (cells with random budding) multiple initial Cdc42 clusters form more frequently [Chiou et al, 2021].…”

Mutations compensating for cell polarity defects change the gene-fitness relationship on a genome-wide scale

“…The structure of this latent pathway and the mechanism through which its manifestation is achieved by compensatory gene deletions is currently unknown. Recent work based on mathematical modeling proposed a Bem1-independent mechanism for polarization that relies on redundancy within the polarity pathway (43), but has not been experimentally verified. In this article, we search for the components of a latent pathway for cell polarity by identifying the genes that are affected by compensatory evolution through a transposon mutagenesis screen (figure 1c).…”