Abstract
A classic problem in population and evolutionary biology is to understand how a population optimizes its fitness in fluctuating environments1,2,3,4. A population might enhance its fitness by allowing individual cells to stochastically transition among multiple phenotypes, thus ensuring that some cells are always prepared for an unforeseen environmental fluctuation. Here we experimentally explore how switching affects population growth by using the galactose utilization network of Saccharomyces cerevisiae. We engineered a strain that randomly transitions between two phenotypes as a result of stochastic gene expression5,6,7,8,9. Each phenotype was designed to confer a growth advantage over the other phenotype in a certain environment. When we compared the growth of two populations with different switching rates, we found that fast-switching populations outgrow slow switchers when the environment fluctuates rapidly, whereas slow-switching phenotypes outgrow fast switchers when the environment changes rarely. These results suggest that cells may tune inter-phenotype switching rates to the frequency of environmental changes.
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Acknowledgements
We would like to thank M. Thattai, S. Tans, A. Raj, J. Gore, S. Rifkin and N. Karahan for helpful discussions and/or comments on the manuscript. This work was supported by National Science Foundation grant PHY-0548484 and US National Institutes of Health grant R01-GM077183. J.T.M. was partially supported by an NSF Graduate Research Fellowship.
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M.A. and A.v.O. conceived the project and designed the experiments. M.A. constructed and characterized the yeast strain used and performed the turbidostat experiments. J.T.M. built the turbidostat and developed the population dynamics model. All authors interpreted the results and wrote the paper.
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Supplementary Figures 1–6, Supplementary Table 1, Supplementary Methods (PDF 351 kb)
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Acar, M., Mettetal, J. & van Oudenaarden, A. Stochastic switching as a survival strategy in fluctuating environments. Nat Genet 40, 471–475 (2008). https://doi.org/10.1038/ng.110
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DOI: https://doi.org/10.1038/ng.110
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