Engineering complex communities by directed evolution.

Chang CY, Vila JCC, Bender M, Li R, Mankowski MC, Bassette M, Borden J, Golfier S, Sanchez PGL, Waymack R, Zhu X, Diaz-Colunga J, Estrela S, Rebolleda-Gomez M, Sanchez A
Nature ecology & evolution 2021
Open on PubMed

Directed evolution has been used for decades to engineer biological systems at or below the organismal level. Above the organismal level, a small number of studies have attempted to artificially select microbial ecosystems, with uneven and generally modest success. Our theoretical understanding of artificial ecosystem selection is limited, particularly for large assemblages of asexual organisms, and we know little about designing efficient methods to direct their evolution. Here, we have developed a flexible modelling framework that allows us to systematically probe any arbitrary selection strategy on any arbitrary set of communities and selected functions. By artificially selecting hundreds of in silico microbial metacommunities under identical conditions, we first show that the main breeding methods used to date, which do not necessarily let communities reach their ecological equilibrium, are outperformed by a simple screen of sufficiently mature communities. We then identify a range of alternative directed evolution strategies that, particularly when applied in combination, are well suited for the top-down engineering of large, diverse and stable microbial consortia. Our results emphasize that directed evolution allows an ecological structure-function landscape to be navigated in search of dynamically stable and ecologically resilient communities with desired quantitative attributes.

9 Figures Extracted
Extended Data Figure 1.
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Non-additive function, costly function, and two empirically motivated functions. (A) Illustration of the different types of community function we have...
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Alternative ecological scenarios with metabolic cross-feeding. Besides the rich medium without cross-feeding shown in the main text, we have included ...
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Functional responses. The resource import rate depends on its concentration in the environments, which can take a linear (type I), Monod (type II), or...
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Alternative Metacommunity sampling approaches. We simulate three metacommunity sampling approaches: i) Each community is seeded with 10 6 cells drawn...
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Different distributions of per capita species contribution to additive community function. Per capita species contribution drawn from i) normal distri...
Figure 1.
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Migrant-pool and propagule strategies are limited in their ability to find new, high-functioning microbial communities. ( A ) We constructed a Python ...
Figure 2.
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Directed evolution as an artificial selection strategy for high-performing communities. ( A ) Directed evolution of microbial communities can be repre...
Figure 3.
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Iteratively combining bottlenecks and migrations to optimize community function selects for high-functioning communities. ( A ) Schematic of iterative...
Figure 4.
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Directed evolution produces communities that are resistant to ecological perturbations. (A) We compare the function and ecological stability of commu...