Abstract
Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well.
Highlights
In their native environments, cells continuously respond to a complexity of environmental stimuli
We have modeled our analysis of these complex environmental interactions using the concepts of gene interaction and genetic epistasis
There are several benefits of using this approach; (1) all the genetic, biochemical, and computational tools and concepts developed for studying gene interactions would become available for studying the effects of the environment, (2) it would allow for easier mechanistic interpretation of the responses to complex environmental stimuli, (3) the contributions of an individual stimulus to altering biological processes can be more elucidated, and (4) it would provide a unifying framework for studying gene-gene, gene-environment and environment-environment interactions
Summary
Cells continuously respond to a complexity of environmental stimuli. Environmental Interactions and Epistasis have been used extensively to study cellular responses to individual and combinations of environmental stimuli [1,10,11,12,13,14,15,16,17] We extend these approaches by developing and testing a novel conceptual framework to study proteomic responses of cells to the combinatorial effects of multiple concurrent environmental factors. There are several benefits of using this approach; (1) all the genetic, biochemical, and computational tools and concepts developed for studying gene interactions would become available for studying the effects of the environment, (2) it would allow for easier mechanistic interpretation of the responses to complex environmental stimuli, (3) the contributions of an individual stimulus to altering biological processes can be more elucidated, and (4) it would provide a unifying framework for studying gene-gene, gene-environment and environment-environment interactions. We validated our approach using an independent publicly available transcriptomic dataset
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