Pleiotropic mutations can rapidly evolve to directly benefit self and cooperative partner despite unfavorable conditions.

Cooperation, paying a cost to benefit others, is widespread. Cooperation can be promoted by pleiotropic 'win-win' mutations which directly benefit self (self-serving) and partner (partner-serving). Previously, we showed that partner-serving should be defined as increased benefit supply rate per intake benefit. Here, we report that win-win mutations can rapidly evolve even under conditions unfavorable for cooperation. Specifically, in a well-mixed environment we evolved engineered yeast cooperative communities where two strains exchanged costly metabolites, lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, mutations repeatedly arose. is self-serving, improving self's growth rate in limiting lysine. is also partner-serving, increasing hypoxanthine release rate per lysine consumption and the steady state growth rate of partner and of community. also arose in monocultures evolving in lysine-limited chemostats. Thus, even without any history of cooperation or pressure to maintain cooperation, pleiotropic win-win mutations may readily evolve to promote cooperation.