The Whi2p-Psr1p/Psr2p complex regulates interference competition and expansion of cells with competitive advantage in yeast colonies

Yeast form complex, highly organized colonies, in which cells undergo spatiotemporal phenotypic differentiation in response to local gradients of nutrients, metabolites and specific signaling molecules. Colony fitness depends on cell interaction, cooperation and division of labor between differentiated cell subpopulations. Here, we describe the regulation and dynamics of expansion of papillae that arise during colony aging and consist of cells that overcome colony regulatory rules and disrupt synchronized colony structure. Using microscopy, we show that papillae specifically expand within the U-cell-subpopulation in differentiated colonies. Papillae emerge more frequently in some strains than in others. Genomic analyses further revealed that the Whi2p-Psr1p/Psr2p complex plays a key role in papillae cell expansion. We show that cells lacking a functional Whi2p-Psr1p/Psr2p complex have a sizable interaction-specific fitness advantage attributable to production of and resistance to a diffusible compound that inhibits growth of other cells. Competitive superiority and high relative fitness of whi2 and psr1psr2 strains are especially pronounced in dense, spatially-structured colonies, and are independent of TORC1 and Msn2p/Msn4p regulators previously associated with Whi2p-Psr1p/Psr2p function. The Whi2p-Psr1p/Psr2p complex function, described here, may be a regulatory mechanism, balancing cell competition and cooperation in dense yeast populations and thus contributing to cell synchronization, pattern formation and expansion of cells with a competitive fitness advantage.