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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- Evolutionary Biology
The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that evolution can result in the emergence and maintenance of more than 100 alleles under HA if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defence; second, the effect of pathogens depends on host condition, with hosts in poorer condition being affected more strongly. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.
