Fitness variation across subtle environmental perturbations reveals local modularity and global pleiotropy of adaptation
Abstract
Building a genotype-phenotype-fitness map of adaptation is a central goal in evolutionary biology. It is difficult even when adaptive mutations are known because it is hard to enumerate which phenotypes make these mutations adaptive. We address this problem by first quantifying how the fitness of hundreds of adaptive yeast mutants responds to subtle environmental shifts. We then model the number of phenotypes these mutations collectively influence by decomposing these patterns of fitness variation. We find that a small number of inferred phenotypes can predict fitness of the adaptive mutations near their original glucose-limited evolution condition. Importantly, inferred phenotypes that matter little to fitness at or near the evolution condition can matter strongly in distant environments. This suggests that adaptive mutations are locally modular—affecting a small number of phenotypes that matter to fitness in the environment where they evolved—yet globally pleiotropic—affecting additional phenotypes that may reduce or improve fitness in new environments.
Data availability
All sequencing data has been deposited to SRA under NIH BioProject number PRJNA641718.
Article and author information
Author details
Funding
National Institutes of Health (R35GM118165)
- Dmitri A Petrov
National Institutes of Health (R35GM133674)
- Kerry Geiler-Samerotte
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Vaughn S Cooper, University of Pittsburgh, United States
Version history
- Received: July 20, 2020
- Accepted: December 2, 2020
- Accepted Manuscript published: December 2, 2020 (version 1)
- Version of Record published: February 12, 2021 (version 2)
Copyright
© 2020, Kinsler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the amino acid-polyamine-organocation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Using in vivo experimental evolution, we evolve two of these transporter genes, AGP1 and PUT4, toward new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches.
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