PT  - JOURNAL ARTICLE
AU  - Robert Egbert
AU  - Leandra Brettner
AU  - David Zong
AU  - Eric Klavins
TI  - Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization
AID  - 10.1101/086900
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 086900
4099  - http://biorxiv.org/content/early/2017/01/07/086900.short
4100  - http://biorxiv.org/content/early/2017/01/07/086900.full
AB  - Cooperation through division of labor underpins biological complexity for organisms and communities. In microbes, stochastic differentiation coupled to programmed cell death drives diverse altruistic behaviors that promote cooperation. Utilizing cell death for developmental multicellular programs requires control over differentiation rate to balance cell proliferation against the utility of sacrifice. However, these behaviors are often controlled by complex regulatory networks and have yet to be demonstrated from first principles. Here we engineered a synthetic developmental gene network that couples stochastic differentiation with programmed cell death to implement a two-member division of labor. Progenitor consumer cells were engineered to grow on cellobiose and differentiate at a controlled rate into self-destructive altruists that release an otherwise sequestered cellulase payload through autolysis. This circuit produces a developmental Escherichia coli consortium that utilizes cellulose for growth. We used an experimentally parameterized model of task switching, payload delivery and nutrient release to set key parameters to achieve overall population growth, liberating 14-23% of the available carbon. An inevitable consequence of engineering self-destructive altruism is the emergence of cheaters that undermine cooperation. We observed cheater phenotypes for consumers and altruists, identified mutational hotspots and developed a predictive model of circuit longeivity. This work introduces the altruistic developmental program as a tool for synthetic biology, demonstrates the utility of population dynamics models to engineer multicellular behaviors and provides a testbed for probing the evolutionary biology of self-destructive altruism.