Conserved rules govern genetic interaction degree across species

Koch, Elizabeth N.; Costanzo, Michael; Bellay, Jeremy; Deshpande, Raamesh; Chatfield-Reed, Kate; Chua, Gordon; D’Urso, Gennaro; Andrews, Brenda; Boone, Charles; Myers, Chad L.

doi:10.1186/gb-2012-13-7-r57

Cited by 52 publications

(61 citation statements)

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“…Even if only a fraction of the S. pombe genetic interaction network has been screened, a number of orthologous genes that have evolved different genetic relationships and play different or additional roles in fission vs. budding yeast have been described (Frost et al 2012;Koch et al 2012). The significant different features of fission yeast MAPK integrity pathway when compared to the S. cerevisiae pathway might imply that both cascades undergo different cellular functions.…”

Section: Discussionmentioning

confidence: 99%

Negative Functional Interaction Between Cell Integrity MAPK Pathway and Rho1 GTPase in Fission Yeast

et al. 2013

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Rho1 GTPase is the main activator of cell wall glucan biosynthesis and regulates actin cytoskeleton in fungi, including Schizosaccharomyces pombe. We have obtained a fission yeast thermosensitive mutant strain carrying the rho1-596 allele, which displays reduced Rho1 GTPase activity. This strain has severe cell wall defects and a thermosensitive growth, which is partially suppressed by osmotic stabilization. In a global screening for rho1-596 multicopy suppresors the pmp1 + gene was identified. Pmp1 is a dual specificity phosphatase that negatively regulates the Pmk1 mitogen-activated protein kinase (MAPK) cell integrity pathway. Accordingly, elimination of Pmk1 MAPK partially rescued rho1-596 thermosensitivity, corroborating the unexpected antagonistic functional relationship of these genes. We found that rho1-596 cells displayed increased basal activation of the cell integrity MAPK pathway and therefore were hypersensitive to MgCl 2 and FK506. Moreover, the absence of calcineurin was lethal for rho1-596. We found a higher level of calcineurin activity in rho1-596 than in wild-type cells, and overexpression of constitutively active calcineurin partially rescued rho1-596 thermosensitivity. All together our results suggest that loss of Rho1 function causes an increase in the cell integrity MAPK activity, which is detrimental to the cells and turns calcineurin activity essential. RHO GTPases are conserved proteins that regulate the actin cytoskeleton organization in all eukaryots (Heasman and Ridley 2008). Additionally, in yeast and other fungi, these GTPases provide the coordinated regulation of cell wall biosynthesis and actin organization, which is required to maintain cell integrity and polarized growth (Levin 2005;Park and Bi 2007;Perez and Cansado 2010). The Schizosaccharomyces pombe genome contains six genes coding Rho GTPases. Among them, rho1 + is essential (Arellano et al. 1996). Rho1 function is mediated by its interaction with at least three different targets: the b(1,3)-glucan synthase (Arellano et al. 1996), which is responsible for the synthesis of the major cell wall component, and the kinases Pck1 and Pck2 Sayers et al. 2000). Through both kinases, Rho1 also regulates the cell wall synthesis. Rho2 also interacts with Pck2 and, therefore, both GTPases regulate the a-D-glucan synthesis through Pck2 (Katayama et al. 1999;Calonge et al. 2000). Lack of Rho1 is lethal, and this phenotype is not suppressed by osmotic stabilization (Arellano et al. 1997), suggesting that defective biosynthesis of the cell wall is not the unique cause of death. On the contrary, Rho2-less cells are viable, although they become slightly rounded and more sensitive to treatment with glucanases (Hirata et al. 1998). Rho2 and Pck2 participate in the activation of the cell integrity mitogen-activated protein kinase (MAPK) signaling pathway (Ma et al. 2006). This signaling cascade responds to different extracellular stress stimuli such as hyper-or hypotonic conditions, oxidative stress, cell wall damaging compounds, and g...

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Section: Discussionmentioning

confidence: 99%

Negative Functional Interaction Between Cell Integrity MAPK Pathway and Rho1 GTPase in Fission Yeast

et al. 2013

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“…[35]. The normalized difference is selected for the comparison of the total number of codons in each block…”

Section: Similarity Measures As Gene Pair Features In Ortholog Detectionmentioning

confidence: 99%

“…The S. cerevisiae -S. pombe dataset represents the union of Inparanoid7.0 and GeneDB ortholog classifications as is described in [35]. On the other hand, the S. cerevisiae -K. lactis and S.…”

Section: Settingsmentioning

confidence: 99%

Big Data Supervised Pairwise Ortholog Detection in Yeasts

Cañizares¹,

Barrio‐García²,

Herrera³

et al. 2017

Yeast - Industrial Applications

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Ortholog are genes in different species, evolving from a common ancestor. Ortholog detection is essential to study phylogenies and to predict the function of unknown genes. The scalability of gene (or protein) pairwise comparisons and that of the classification process constitutes a challenge due to the ever-increasing amount of sequenced genomes. Ortholog detection algorithms, just based on sequence similarity, tend to fail in classification, specifically, in Saccharomycete yeasts with rampant paralogies and gene losses. In this book chapter, a new classification approach has been proposed based on the combination of pairwise similarity measures in a decision system that consider the extreme imbalance between ortholog and non-ortholog pairs. Some new gene pair similarity measures are defined based on protein physicochemical profiles, gene pair membership to conserved regions in related genomes, and protein lengths. The efficiency and scalability of the calculation of these measures are analyzed to propose its implementation for big data. In conclusion, evaluated supervised algorithms that manage big and imbalanced data showed high effectiveness in Saccharomycete yeast genomes.

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“…Using systems biology and network analysis in studying phenotypes as a substitute or a complementary approach to single gene prioritization in African populations will yield valuable information. Networks are regarded as conserved evolutionary units that can undergo selection [4,5]. Evolutionary plasticity of genetic interaction networks [6] adds another interesting perspective.…”

Section: Effective Genomicsmentioning

confidence: 99%