RT Journal Article SR Electronic T1 Spatially-constrained growth enhances conversional meltdown JF bioRxiv FD Cold Spring Harbor Laboratory SP 027292 DO 10.1101/027292 A1 Maxim O. Lavrentovich A1 Mary E. Wahl A1 Andrew W. Murray A1 David R. Nelson YR 2015 UL http://biorxiv.org/content/early/2015/09/21/027292.abstract AB 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.”