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Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization

View ORCID ProfileRobert Egbert, Leandra Brettner, David Zong, Eric Klavins
doi: https://doi.org/10.1101/086900
Robert Egbert
1University of Washington, Electrical Engineering (Seattle, WA, USA)
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Leandra Brettner
2University of Washington, Bioengineering (Seattle, WA, USA)
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David Zong
2University of Washington, Bioengineering (Seattle, WA, USA)
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Eric Klavins
1University of Washington, Electrical Engineering (Seattle, WA, USA)
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Abstract

Stochastic differentiation and programmed cell death are common developmental processes in microbes, driving diverse altruistic behaviors that promote cooperation. Utilizing cell death in developmental programs requires control over the rate of differentiation to balance cell proliferation against the utility of sacrifice. However, the regulatory networks that control these behaviors are often complex and have yet to be successfully harnessed as biotechnology. 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 cellobiose consumer cells were engineered to grow on cellobiose and differentiate at a controlled rate into self-destructive altruists that release an otherwise sequestered cellulase enzyme payload through autolysis to form a developmental Escherichia coli consortium that utilizes cellulose for growth. We used an experimentally parameterized model of task switching, payload delivery and cellulose conversion to nutrients to set key parameters to achieve overall population growth supported by cellulase release, liberating 14-23% of the available carbon. An inevitable consequence of engineering altruistic developmental behaviors is the emergence of cheaters that undermine cooperation. We observed cheater phenotypes for consumers and altruists, identified mutational hotspots and constructed a predictive model of circuit longeivity based on mutation rate estimates for each mode of evolutionary escape. This work introduces the altruistic developmental program as a new tool for synthetic biology, demonstrates the utility of population dynamics models to engineer complex phenotypes and provides a testbed for probing the evolutionary biology of self-destructive altruism.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 12, 2016.
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Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization
Robert Egbert, Leandra Brettner, David Zong, Eric Klavins
bioRxiv 086900; doi: https://doi.org/10.1101/086900
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Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization
Robert Egbert, Leandra Brettner, David Zong, Eric Klavins
bioRxiv 086900; doi: https://doi.org/10.1101/086900

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