TY - JOUR T1 - Spatially-constrained growth enhances conversional meltdown JF - bioRxiv DO - 10.1101/027292 SP - 027292 AU - Maxim O. Lavrentovich AU - Mary E. Wahl AU - Andrew W. Murray AU - David R. Nelson Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/09/21/027292.abstract N2 - Cells that mutate or commit to a specialized function (differentiate) often undergo conversions that are effectively irreversible. Slowed growth of converted cells can act as a form of selection, balancing unidirectional conversion to maintain both cell types at a steady-state ratio. When conversion is insufficiently counterbalanced by selection, the original cell type will ultimately be lost, often with negative impacts on the population’s fitness. The critical relationship between selection and conversion for maintenance of unconverted cells and the ratio between cell types at steady state (if one exists) depend on the spatial circumstances under which cells proliferate. We present analytical predictions for growth in several biologically-relevant geometries – well-mixed liquid media, radiallyexpanding colonies on flat surfaces, and linear fronts – by employing analogies to the directed percolation transition from non-equilibrium statistical physics. We test these predictions in vivo using a yeast strain engineered to undergo irreversible conversion: this synthetic system permits cell type-specific fluorescent labeling and exogenous variation of the relative growth and conversion rates. We find that populations confined to grow on a surface are more susceptible to fitness loss via a conversion-induced “meltdown.” ER -