Evolutionary principles of modular gene regulation in yeasts

Thompson, Dawn; Roy, Sushmita; Chan, M.K.; Styczynsky, Mark P.; Pfiffner, Jenna; French, Courtney; Socha, Amanda; Thielke, Anne; Napolitano, Sara; Muller, Paul; Kellis, M; Konieczka, Jay H.; Wapinski, Ilan; Regev, Aviv

doi:10.7554/elife.00603

Cited by 79 publications

(132 citation statements)

References 72 publications

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“…The contribution of paralogs resulting from WGD to regulatory divergence is more pronounced and longer lasting than the contribution of genes arising through small-scale duplications [25 ]. This regulatory divergence can drive regulatory network evolution and rewiring and lead to regulatory innovation [26 ,27,28].…”

Section: Main Text Of Reviewmentioning

confidence: 99%

Experimental evolution of the model eukaryote Saccharomyces cerevisiae yields insight into the molecular mechanisms underlying adaptation

Voordeckers

Verstrepen²

2015

Current Opinion in Microbiology

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Understanding how changes in DNA drive the emergence of new phenotypes and fuel evolution remains a major challenge. One major hurdle is the lack of a fossil record of DNA that allows linking mutations to phenotypic changes. However, the emergence of high-throughput sequencing technologies now allows sequencing genomes of natural and experimentally evolved microbial populations to study how mutations arise and spread through a population, how new phenotypes arise and how this ultimately leads to adaptation. Here, we highlight key studies that have increased our mechanistic understanding of evolution. We specifically focus on the model eukaryote Saccharomyces cerevisiae because its relatively short replication time, much-studied biology and available molecular toolbox have made it a prime model for molecular evolution studies.

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Section: Main Text Of Reviewmentioning

confidence: 99%

Experimental evolution of the model eukaryote Saccharomyces cerevisiae yields insight into the molecular mechanisms underlying adaptation

Voordeckers

Verstrepen²

2015

Current Opinion in Microbiology

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“…Cells were cold methanol quenched exactly as described in Thompson et al (2013) right before the addition of 5 mM H 2 O 2 or 5 and 15 min post H 2 O 2 addition. Hydrogen peroxide is a suitable proxy for host response as it is the most common ROS used by the immune system during respiratory burst (Iles and Forman 2002), and passes through the cell membrane, reaching the cytoplasm quickly (Kohchi et al 2009).…”

Section: Expression Profilingmentioning

confidence: 99%

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

et al. 2017

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Almost all humans are colonized with Candida albicans. However, in immunocompromised individuals, this benign commensal organism becomes a serious, life-threatening pathogen. Here, we describe and analyze the regulatory networks that modulate innate responses in the host niches. We identified Zcf15 and Zcf29, two Zinc Cluster transcription Factors (ZCF) that are required for C. albicans virulence. Previous sequence analysis of clinical C. albicans isolates from immunocompromised patients indicates that both ZCF genes diverged during clonal evolution. Using in vivo animal models, ex vivo cell culture methods, and in vitro sensitivity assays, we demonstrate that knockout mutants of both ZCF15 and ZCF29 are hypersensitive to reactive oxygen species (ROS), suggesting they help neutralize the host-derived ROS produced by phagocytes, as well as establish a sustained infection in vivo. Transcriptomic analysis of mutants under resting conditions where cells were not experiencing oxidative stress revealed a large network that control macro and micronutrient homeostasis, which likely contributes to overall pathogen fitness in host niches. Under oxidative stress, both transcription factors regulate a separate set of genes involved in detoxification of ROS and down-regulating ribosome biogenesis. ChIP-seq analysis, which reveals vastly different binding partners for each transcription factor (TF) before and after oxidative stress, further confirms these results. Furthermore, the absence of a dominant binding motif likely facilitates their mobility, and supports the notion that they represent a recent expansion of the ZCF family in the pathogenic Candida species. Our analyses provide a framework for understanding new aspects of the interface between C. albicans and host defense response, and extends our understanding of how complex cell behaviors are linked to the evolution of TFs.

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“…It was previously reported that duplicate genes evolve rapidly in expression pattern (Li et al 2005;Thompson et al 2013). If the inferred neofunctionalization after gene duplication is attributable to gains of new expression patterns, duplicates with fitness gains are expected to have larger expression differences and smaller expression correlations across cell cycle stages or media compared with those without fitness gains.…”

Section: Gains Of Protein-protein Interactions Could Explain the Neofmentioning

confidence: 99%

Genomic evidence for adaptation by gene duplication

2014

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Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing postduplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation.

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Evolutionary principles of modular gene regulation in yeasts

Cited by 79 publications

References 72 publications

Experimental evolution of the model eukaryote Saccharomyces cerevisiae yields insight into the molecular mechanisms underlying adaptation

Experimental evolution of the model eukaryote Saccharomyces cerevisiae yields insight into the molecular mechanisms underlying adaptation

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

Genomic evidence for adaptation by gene duplication

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