Elucidating the genome wide consequences of rewiring the yeast polarity network

Polarity establishment plays an important role in biological functions that are observed throughout the tree of life. In the budding yeast Saccharomyces cerevisiae a polarized spot of the evolutionary conserved protein Cdc42 marks the position of new bud formation, making polarity establishment an essential part of the cell cycle. Due to its role as a model organism, many of the proteins that are involved in regulating the polarized distribution of Cdc42 have been identified in S. cerevisiae. Interestingly, the effects of losing a protein considered to be central in polarity establishment (Bem1) can be compensated during evolution by the subsequent deletion of two other proteins (Bem3 and Nrp1) rather than requiring the emergence of a new protein that takes over the lost function. This suggests that other proteins in the cell have changed their interaction profile to buffer the polarity defects by establishing an alternative pathway for Cdc42 polarization. Here, we use a recently developed transposon mutagenesis assay for yeast to uncover the key players in this alternative pathway based on their altered essentiality after the deletion of Bem1, Bem3 and Nrp1. We find that the evolutionary repair of polarity establishment has consequences for a diverse set of cellular processes seemingly unrelated to cell polarity. Surprisingly, we observe that the reorganization of the polarity network not only leads to an increased essentiality, but also an increased dispensability of genes related to these processes.