Self-organization as a buffer for evolution, using cell polarity in budding yeast as a model

The successful survival and proliferation of living cells is based on incredibly complex networks consisting of large numbers of mutually interacting proteins. Core cellular functions maintained by these networks are typically highly robust against mutational perturbations. How the evolutionary robustness of core functions is established remains an open question. As a concrete model system, we study polarization in the budding yeast Saccharomyces cerevisiae. Polarization in budding yeast is centered around the small Rho GTPase Cdc42, whose accumulation on the membrane drives cell budding at a single site. The polarization machinery in yeast has previously been shown to be highly resilient to genetic perturbations: crippling of the network by deleting a near-essential scaffold protein gene (BEM1) is followed by a reproducible evolutionary trajectory, in which subsequent inactivation of several related genes in the network recovers near wild type fitness levels.

We propose that evolutionary resilience of functional protein networks is facilitated by self-organizing properties, i.e. the idea that the components of a network can reactively change their behavior and mutual relationships to provide a buffer against perturbing effects. Thus, we expect that mutational perturbations are countered by a collective response of the network, as opposed to e.g. direct functional compensation by another similar network component. To test our hypothesis, we will experimentally map out the behavior of a set of core polarization proteins in space and time along the evolutionary trajectory described above by means of high throughput fluorescence microscopy. Furthermore, we seek a novel paradigm to describe how self-organizing properties of the polarization network can facilitate evolutionary resilience. To this end, we will explore whether multicomponent phase separation of polarization proteins can be a relevant framework to describe the behavior of the system and its evolution.