Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway
- Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, United States
- Yale School of Medicine, United States
Abstract
Although combinatorial regulation is a common feature in gene regulatory networks, how it evolves and affects network structure and function is not well understood. In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are required for gene induction and survival during phosphate starvation. In the related human commensal C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate starvation and is only partially required for inducing PHO genes. Phylogenetic survey suggests that reduced dependence on Pho2 evolved in C. glabrata and closely related species. In S. cerevisiae, less Pho2-dependent Pho4 orthologs induce more genes. In C. glabrata, its Pho4 binds to more locations and induces three times as many genes as Pho4 in S. cerevisiae does. Our work shows how evolution of combinatorial regulation allows for rapid expansion of a gene regulatory network's targets, possibly extending its physiological functions.
Data availability
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Evolution of Reduced Co-Activator Dependence Led to Target Expansion of a Starvation Response PathwayPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE97801).
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Integrated approaches reveal determinants of genome-wide binding and function of the transcription factor Pho4.Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE29506).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Bin Z He
- Xu Zhou
- Erin K O'Shea
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, He 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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Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway
eLife 6:e25157.
https://doi.org/10.7554/eLife.25157
Further reading
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- Computational and Systems Biology
- Evolutionary Biology
As pathogens spread in a population of hosts, immunity is built up, and the pool of susceptible individuals are depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with rapid antigenic evolution and frequent emergence of immune evasive variants. However, the host’s immune systems adapt, and older immune responses wane, such that escape variants only enjoy a growth advantage for a limited time. If variant growth dynamics and reshaping of host-immunity operate on comparable time scales, viral adaptation is determined by eco-evolutionary interactions that are not captured by models of rapid evolution in a fixed environment. Here, we use a Susceptible/Infected model to describe the interaction between an evolving viral population in a dynamic but immunologically diverse host population. We show that depending on strain cross-immunity, heterogeneity of the host population, and durability of immune responses, escape variants initially grow exponentially, but lose their growth advantage before reaching high frequencies. Their subsequent dynamics follows an anomalous random walk determined by future escape variants and results in variant trajectories that are unpredictable. This model can explain the apparent contradiction between the clearly adaptive nature of antigenic evolution and the quasi-neutral dynamics of high-frequency variants observed for influenza viruses.
