Collaborate or Collapse: Experimental and Mathematical Analysis of a Synthetic Cooperative System

Wenjing Shou
Fred Hutchinson Cancer Research Institute

Cooperative interactions are key to diverse biological phenomena ranging from multicellularity to mutualism. Such diversity makes the ability to create and control cooperation desirable for potential applications in areas as varied as agriculture, pollutant treatment, and medicine. I show that persistent cooperation can be engineered by introducing a small set of genetic modifications into previously non-interacting cell populations. Specifically, I constructed of a synthetic obligatory cooperative system, termed CoSMO (for Cooperation that is Synthetic and Mutually Obligatory), that consists of a pair of non-mating yeast strains, each supplying an essential metabolite to the other strain. The behavior of the two strains in isolation however revealed unintended constraints that restrict cooperation, such as asymmetry in starvation tolerance and delays in nutrient release until near cell death. Yet, the joint system is shown mathematically and experimentally to be viable over a wide range of initial conditions, with oscillating population ratio settling to a value predicted by nutrient supply and consumption. Unexpectedly, even in the absence of explicitly engineered mechanisms to stabilize cooperation, the cooperative system can consistently develop increased ability to survive reductions in population density. Extending synthetic biology from the design of genetic circuits to the engineering of ecological interactions, CoSMO provides a quantitative system for linking processes at the cellular level to the collective behavior at the system level as well as a genetically tractable system for studying the evolution of cooperation.