A modeling study of budding yeast colony formation and its relationship to budding pattern and aging

Budding yeast, which undergoes polarized growth during budding and mating, has been a useful model system to study cell polarization. Bud sites are selected differently in haploid and diploid yeast cells: haploid cells bud in an axial manner, while diploid cells bud in a bipolar manner. While previous studies have been focused on the molecular details of the bud site selection and polarity establishment, not much is known about how different budding patterns give rise to different functions at the population level. In this paper, we develop a two-dimensional agent-based model to study budding yeast colonies with cell-type specific biological processes, such as budding, mating, mating type switch, consumption of nutrients, and cell death. The model demonstrates that the axial budding pattern enhances mating probability at an early stage and the bipolar budding pattern improves colony development under nutrient limitation. Our results suggest that the frequency of mating type switch might control the trade-off between diploidization and inbreeding. The effect of cellular aging is also studied through our model. Based on the simulations, colonies initiated by an aged haploid cell show declined mating probability at an early stage and recover as the rejuvenated offsprings become the majority. Colonies initiated with aged diploid cells do not show disadvantage in colony expansion possibly due to the fact that young cells contribute the most to colony expansion.
Author summary Budding yeast is a model organism in understanding fundamental aspects of eukaryotic cells, such as cell polarization and cell aging. Previously, extensive research has focused on the molecular mechanisms of biological processes in yeast, but many questions regarding yeast budding remain unsolved. For example, how do different budding patterns affect yeast colony growth? How does declined spatial order due to aging impact the colony at the population level? To address these questions, we developed a computational agent-based model, which incorporates key biological processes, the effect of aging, as well as cell-environment interaction. We performed and analyzed a large number of simulations for a variety of situations, and obtained insightful results. We found that axial budding pattern enhances the percentage of diploid cells at early stage and bipolar budding pattern improves colony development under nutrient limitation; the frequency of mating type switch might control the trade-off between diploidization and inbreeding; aging affects the percentage of diploid cells in colonies initiated by a single haploid cell, but does not have much influence in the expansion of colonies initiated by diploid cells. The framework of the model can be extended to study other important systems, such as tissue with stem cell lineage.