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High-Throughput Live Imaging of Microcolonies to Measure Heterogeneity in Growth and Gene Expression
Published on: April 18, 2021
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Negative frequency-dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population
David Healey1, Kevin Axelrod2, Jeff Gore3
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Molecular Systems Biology
|August 5, 2016
Summary
Microbial cells can be phenotypically diverse due to negative frequency-dependent interactions, not just environmental uncertainty. This study shows yeast GAL network heterogeneity arises from these interactions, favoring rare phenotypes.
Area of Science:
- Microbiology and Evolutionary Biology
- Systems Biology
- Genetics and Genomics
Background:
- Clonal microbial populations exhibit phenotypic heterogeneity, often attributed to bet-hedging against environmental unpredictability.
- Evolutionary game theory proposes negative frequency-dependent interactions as an alternative driver of such heterogeneity, where rare phenotypes are favored.
Purpose of the Study:
- To experimentally investigate the role of negative frequency-dependent interactions in driving phenotypic heterogeneity within microbial populations.
- To examine the yeast GAL network's response to mixed sugar environments as a model system for studying this phenomenon.
Main Methods:
- Utilized the yeast GAL network in a mixed glucose and galactose environment to observe stochastic bimodal activation.
- Conducted invasion assays to assess the viability of GAL-ON and GAL-OFF phenotypes when rare.
- Employed laboratory evolution experiments to induce de novo evolution of phenotypic heterogeneity from pure strategist populations.
Main Results:
- Demonstrated that both GAL-ON and GAL-OFF phenotypes can invade when rare in a mixed sugar environment, leading to a stable mix.
- Confirmed that this stable mix of phenotypes is not necessarily optimal for population growth, aligning with theoretical predictions.
- Showed that the wild-type mixed strategist GAL network can invade and is resistant to invasion by pure strategists.
Conclusions:
- Provided experimental evidence that negative frequency-dependent interactions can be a significant factor in the development of phenotypic heterogeneity in clonal microbial populations.
- Established the yeast GAL network as a model system for understanding how ecological interactions can shape microbial diversity.
- Highlighted that environmental conditions, such as mixed resources, can directly select for and evolve clonal phenotypic heterogeneity.
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