Q&A: Epistasis

Molecular and Cellular Biolog

GSA Launches G3: Genes | Genomes | Genetics

We are proud to present the inaugural issue of G3: Genes | Genomes | Genetics, an open-access journal published by the Genetics Society of America (GSA). The journal’s team of over 60 associate editors and 4 section editors, all practicing scientists—your peers—have come together to form a new, open-access journal with a unique mission and vision. The Editorial Board of G3 taps the expertise of the community of geneticists in the widest sense, from microbes to humans, from individuals to populations, and from classic “wet lab” experimentation to the most recent innovations in bioinformatics

Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK and NuA4 component Tra1 to multiple cellular processes

<p>Abstract</p> <p>Background</p> <p>Tra1 is an essential 437-kDa component of the <it>Saccharomyces cerevisiae </it>SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. To identify genetic interactions for <it>TRA1 </it>and provide insight into its function we have performed a systematic genetic array analysis (SGA) on <it>tra1</it>_{<it>SRR</it>3413}, an allele that is defective in transcriptional regulation.</p> <p>Results</p> <p>The SGA analysis revealed 114 synthetic slow growth/lethal (SSL) interactions for <it>tra1</it>_{<it>SRR</it>3413}. The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. In addition many of the genes have roles in the cellular response to stress. A hierarchal cluster analysis revealed that the pattern of SSL interactions for <it>tra1</it>_{<it>SRR</it>3413}most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. Consistent with a role for Tra1 in cellular stress, the <it>tra1</it>_{<it>SRR</it>3413}strain was sensitive to rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we show that Tra1 is principally localized to the nucleus.</p> <p>Conclusion</p> <p>We have demonstrated a genetic association of Tra1 with nuclear, mitochondrial and membrane processes. The identity of the SSL genes also connects Tra1 with cellular stress, a result confirmed by the sensitivity of the <it>tra1</it>_{<it>SRR</it>3413}strain to a variety of stress conditions. Based upon the nuclear localization of GFP-Tra1 and the finding that deletion of the Ada components of the SAGA complex result in similar phenotypes as <it>tra1</it>_{<it>SRR</it>3413}, we suggest that the effects of <it>tra1</it>_{<it>SRR</it>3413}are mediated, at least in part, through its role in the SAGA complex.</p

G3, GENETICS, and the GSA: Two Journals, One Mission

With the June launch of its open-access journal G3: Genes | Genomes | Genetics, the Genetics Society of America (GSA) now offers two peer-edited journals. The missions of G3 and GENETICS are fundamentally the same: to provide a forum for timely communication of the latest findings in genetics, selected by editors who are the authors' peers. But the scopes of the two journals are different. Why offer two journals

Resolved Millimeter Observations of the HR 8799 Debris Disk

We present 1.3 millimeter observations of the debris disk surrounding the HR 8799 multi-planet system from the Submillimeter Array to complement archival ALMA observations that spatially filtered away the bulk of the emission. The image morphology at $3.8$ arcsecond (150 AU) resolution indicates an optically thin circumstellar belt, which we associate with a population of dust-producing planetesimals within the debris disk. The interferometric visibilities are fit well by an axisymmetric radial power-law model characterized by a broad width, $\Delta R/R\gtrsim 1$. The belt inclination and orientation parameters are consistent with the planet orbital parameters within the mutual uncertainties. The models constrain the radial location of the inner edge of the belt to $R_\text{in}= 104_{-12}^{+8}$ AU. In a simple scenario where the chaotic zone of the outermost planet b truncates the planetesimal distribution, this inner edge location translates into a constraint on the planet~b mass of $M_\text{pl} = 5.8_{-3.1}^{+7.9}$ M$_{\rm Jup}$. This mass estimate is consistent with infrared observations of the planet luminosity and standard hot-start evolutionary models, with the uncertainties allowing for a range of initial conditions. We also present new 9 millimeter observations of the debris disk from the Very Large Array and determine a millimeter spectral index of $2.41\pm0.17$. This value is typical of debris disks and indicates a power-law index of the grain size distribution $q=3.27\pm0.10$, close to predictions for a classical collisional cascade.Comment: 18 pages, 7 figures, accepted by Ap

Protein Complexes are Central in the Yeast Genetic Landscape

If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ∼5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available

Genetic profiling of protein burden and nuclear export overload

Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload

The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

We thank Cowen lab members for helpful discussions. We also thank David Rogers (University of Tennessee) for sharing microarray analysis of the CAS5 homozygous mutant, and Li Ang (University of Macau) for assistance in optimizing the ChIP-Seq experiments. J.L.X. is supported by a Canadian Institutes of Health Research Doctoral award and M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072). B.T.G. holds an Ontario Graduate Scholarship. C.B. and B.J.A. are supported by the Canadian Institutes of Health Research Foundation Grants (FDN-143264 and -143265). D.J.K. is supported by a National Institute of Allergy and Infectious Diseases grant (1R01AI098450) and J.D.L.C.D. is supported by the University of Rochester School of Dentistry and Medicine PREP program (R25 GM064133). A.S. is supported by the Creighton University and the Nebraska Department of Health and Human Services (LB506-2017-55). K.H.W. is supported by the Science and Technology Development Fund of Macau S.A.R. (FDCT; 085/2014/A2). L.E.C. is supported by the Canadian Institutes of Health Research Operating Grants (MOP-86452 and MOP-119520), the Natural Sciences and Engineering Council (NSERC) of Canada Discovery Grants (06261 and 462167), and an NSERC E.W.R. Steacie Memorial Fellowship (477598).Peer reviewedPublisher PD