Environmental Stress Can Favor Cooperation by Triggering an Adaptive Race Between Cooperators and Cheaters
Waite, Adam James
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Resolving the apparent paradox of the almost universal success of cooperation despite its vulnerability to cheating has been the focus of decades of theoretical and experimental research. Cooperators pay a cost to produce common goods that can be used by any individual, including cheaters. Cheaters consume but do not contribute fairly to the production of common goods, and are therefore more fit than cooperators. Cheaters should therefore displace cooperators, resulting in the eventual demise of cooperation known as “the tragedy of the commons.” How can cooperation persist despite the threat of cheaters? Previous research has shown that mechanisms such as spatial clustering of cooperators or cheater-sanctioning can help cooperation survive cheating. I have discovered an entirely new mechanism—adaptation to environmental stress—that favors cooperation over cheating. I started by testing whether the known pro-cooperation mechanisms are the only mechanisms that can stabilize cooperation. I employed a synthetic yeast cooperator-cheater system based on the release or exploitation of essential metabolites to systematically remove all known cheater control mechanisms, which would have been impossible if using natural cooperative systems. Surprisingly, I found that despite cooperators being less fit than cheaters, some cocultures rapidly purged cheaters, while in others cheaters dominated and drove cocultures and themselves extinct. Using deep sequencing and phenotypic analyses, I demonstrated the molecular mechanism responsible for this unanticipated outcome. Essentially, the nutrient-limited cooperative environment acted as a stress on both cooperators and cheaters. I found that this stress created a selective pressure which triggered an “adaptive race” between cooperators and cheaters to sample from the same pool of fitness-enhancing mutations. If cooperators sampled the best mutation, cooperators would win the race and continue to proliferate. If cheaters won the race, rapid self-extinction ensued due to the tragedy of the commons. I found evidence both in my system and in a natural cooperative bacteria system that the adaptive race can be triggered by previously-encountered environmental stresses. Importantly, I showed stress can synergize with a spatially-structured environment to promote cooperation. I mathematically modeled the biologically realistic scenario of separate populations containing both cooperators and cheaters which interact through occasional migration. I found that cooperators are less likely to be destroyed by cheaters if environmental stresses are present. In collaboration with Ben Kerr lab at UW, we tested my model using the cooperative bacterium <italic>Pseudomonas aeruginosa</italic>, which produces proteases to digest extracellular proteins. Cheater cells do not produce proteases and are fitter than cooperators. We showed that cooperation can be stabilized even when spatial structure is random and transient, but only when an environmental stress—antibiotics in this case—elicits an adaptive race between cooperators and cheaters. We are testing whether this phenomenon is due to a process called “niche-hiking”: Isolated cooperators, by creating an environment suitable for growth, may sample more beneficial mutations in the stressful environment than isolated cheaters, which cannot grow. The deleterious cooperative phenotype can thus "hitchhike" on the beneficial mutations sampled as a result of cooperator-associated niche construction. Finally, I found considerable non-genetic heterogeneity in response to the environmental stress of nutrient limitation, and tracked it to its molecular source: differential ability of individual cells to express the high-affinity lysine permease Lyp1p, at the cell surface. This heterogeneity could potentially provide enough variation to fuel the adaptive race when populations are too small to contain any high-fitness mutants. In sum, previous theoretical and experimental work on cooperation and cheating has always assumed a constant environment in which adaptation is precluded. I used mathematical modeling as well as engineered and natural systems to demonstrate, for the first time, the importance of adaptation to stressful environmental changes—a biological reality as ubiquitous as spatial structure—in facilitating cooperation.