Precise Replacement of Saccharomyces cerevisiae Proteasome Genes with Human Orthologs by an Integrative Targeting Method
Artificial induction of a chromosomal double-strand break in Saccharomyces cerevisiae enhances the frequency of integration of homologous DNA fragments into the broken region by up to several orders of magnitude. The process of homologous repair can be exploited to integrate, in principle, any foreign DNA into a target site, provided the introduced DNA is flanked at both the 5' and 3' ends by sequences homologous to the region surrounding the double-strand break. I have developed tools to precisely direct double-strand breaks to chromosomal target sites with the meganuclease I-SceI and select integration events at those si...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Yellman, C. M. Tags: Investigations Source Type: research
Low Oxygen Stress During Early Development Influences Regulation of Hypoxia-Response Genes in Farmed Atlantic Salmon (Salmo salar)
Survival and growth of developing salmonids are negatively affected by low oxygen levels within gravel nests in natural streams, and hypoxic stress is often experienced by farmed Atlantic salmon (Salmo salar) within hatcheries. Exposure to hypoxia during early development may have long-lasting effects by altering epigenetic marks and gene expression in oxygen regulatory pathways. Here, we examine the transcriptomic response to low dissolved oxygen (DO) in post-hatch salmon reared continuously in 30%, 60% or 100% DO from fertilization until start of feeding. RNA sequencing revealed multiple differentially expressed genes, i...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Kelly, T., Johnsen, H., Burgerhout, E., Tveiten, H., Thesslund, T., Andersen, O., Robinson, N. Tags: Investigations Source Type: research
Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX)
In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (P < 0.001). Further, we observed strong strain-by-treatment interactions for m...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Giusti-Rodriguez, P., Xenakis, J. G., Crowley, J. J., Nonneman, R. J., DeCristo, D. M., Ryan, A., Quackenbush, C. R., Miller, D. R., Shaw, G. D., Zhabotynsky, V., Sullivan, P. F., Manuel de Villena, F. P., Zou, F. Tags: Multiparental Populations Source Type: research
The Genomic Landscape of Divergence Across the Speciation Continuum in Island-Colonising Silvereyes (Zosterops lateralis)
Inferring the evolutionary dynamics at play during the process of speciation by analyzing the genomic landscape of divergence is a major pursuit in population genomics. However, empirical assessments of genomic landscapes under varying evolutionary scenarios that are known a priori are few, thereby limiting our ability to achieve this goal. Here we combine RAD-sequencing and individual-based simulations to evaluate the genomic landscape of divergence in the silvereye (Zosterops lateralis). Using pairwise comparisons that differ in divergence timeframe and the presence or absence of gene flow, we document how genomic patter...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Sendell-Price, A. T., Ruegg, K. C., Anderson, E. C., Quilodran, C. S., Van Doren, B. M., Underwood, V. L., Coulson, T., Clegg, S. M. Tags: Investigations Source Type: research
Phantom Epistasis in Genomic Selection: On the Predictive Ability of Epistatic Models
Genomic selection uses whole-genome marker models to predict phenotypes or genetic values for complex traits. Some of these models fit interaction terms between markers, and are therefore called epistatic. The biological interpretation of the corresponding fitted effects is not straightforward and there is the threat of overinterpreting their functional meaning. Here we show that the predictive ability of epistatic models relative to additive models can change with the density of the marker panel. In more detail, we show that for publicly available Arabidopsis and rice datasets, an initial superiority of epistatic models o...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Schrauf, M. F., Martini, J. W. R., Simianer, H., de los Campos, G., Cantet, R., Freudenthal, J., Korte, A., Munilla, S. Tags: Genomic Prediction Source Type: research
Protein Interactions of the Mechanosensory Proteins Wsc2 and Wsc3 for Stress Resistance in Saccharomyces cerevisiae
This study defines roles for Wsc2p and Wsc3p and their interacting protein partners in the cell wall integrity signaling and cell survival mechanisms that respond to treatments with fluconazole and hydrogen peroxide. By combined genetic and biochemical approaches, we report the discovery of 12 novel protein interactors of Wsc2p and Wsc3p. Of these, Wsc2p interacting partners Gtt1p and Yck2p, have opposing roles in the resistance and sensitivity to fluconazole treatments respectively. The interaction of Wsc2p with Ras2p was confirmed by iMYTH and IP-MS approaches and is shown to play a dominant role in response to oxidative...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Velez-Segarra, V., Gonzalez-Crespo, S., Santiago-Cartagena, E., Vazquez-Quinones, L. E., Martinez-Matias, N., Otero, Y., Zayas, J. J., Siaca, R., del Rosario, J., Mejias, I., Aponte, J. J., Collazo, N. C., Lasso, F. J., Snider, J., Jessulat, M., Aoki, H., Tags: Investigations Source Type: research
Loss of the Antimicrobial Peptide Metchnikowin Protects Against Traumatic Brain Injury Outcomes in Drosophila melanogaster
Neuroinflammation is a major pathophysiological feature of traumatic brain injury (TBI). Early and persistent activation of innate immune response signaling pathways by primary injuries is associated with secondary cellular injuries that cause TBI outcomes to change over time. We used a Drosophila melanogaster model to investigate the role of antimicrobial peptides (AMPs) in acute and chronic outcomes of closed-head TBI. AMPs are effectors of pathogen and stress defense mechanisms mediated by the evolutionarily conserved Toll and Immune-deficiency (Imd) innate immune response pathways that activate Nuclear Factor kappa B (...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Swanson, L. C., Rimkus, S. A., Ganetzky, B., Wassarman, D. A. Tags: Investigations Source Type: research
Transcriptome Analyses of Candida albicans Biofilms, Exposed to Arachidonic Acid and Fluconazole, Indicates Potential Drug Targets
Candida albicans is an opportunistic yeast pathogen within the human microbiota with significant medical importance because of its pathogenic potential. The yeast produces highly resistant biofilms, which are crucial for maintaining infections. Though antifungals are available, their effectiveness is dwindling due to resistance. Alternate options that comprise the combination of existing azoles and polyunsaturated fatty acids, such as arachidonic acid (AA), have been shown to increase azoles susceptibility of C. albicans biofilms; however, the mechanisms are still unknown. Therefore, transcriptome analysis was conducted on...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Kuloyo, O., Fourie, R., Cason, E., Albertyn, J., Pohl, C. H. Tags: Investigations Source Type: research
The Genome Sequence of the Jean-Talon Strain, an Archeological Beer Yeast from Quebec, Reveals Traces of Adaptation to Specific Brewing Conditions
The genome sequences of archeological Saccharomyces cerevisiae isolates can reveal insights about the history of human baking, brewing and winemaking activities. A yeast strain called Jean-Talon was recently isolated from the vaults of the Intendant’s Palace of Nouvelle France on a historical site in Québec City. This site was occupied by breweries from the end of the 17th century until the middle of the 20th century when poisoning caused by cobalt added to the beer led to a shutdown of brewing activities. We sequenced the genome of the Jean-Talon strain and reanalyzed the genomes of hundreds of strains to det...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Fijarczyk, A., Henault, M., Marsit, S., Charron, G., Fischborn, T., Nicole-Labrie, L., Landry, C. R. Tags: Investigations Source Type: research
cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans
Identifying the mechanisms behind neuronal fate specification are key to understanding normal neural development in addition to neurodevelopmental disorders such as autism and schizophrenia. In vivo cell fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We used a comparative transcriptome approach to examine the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcrip...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Aquino-Nunez, W., Mielko, Z. E., Dunn, T., Santorella, E. M., Hosea, C., Leitner, L., McCalla, D., Simms, C., Verola, W. M., Vijaykumar, S., Hudson, M. L. Tags: Investigations Source Type: research
Long-Term Reciprocal Gene Flow in Wild and Domestic Geese Reveals Complex Domestication History
Hybridization has frequently been observed between wild and domestic species and can substantially impact genetic diversity of both counterparts. Geese show some of the highest levels of interspecific hybridization across all bird orders, and two of the goose species in the genus Anser have been domesticated providing an excellent opportunity for a joint study of domestication and hybridization. Until now, knowledge of the details of the goose domestication process has come from archaeological findings and historical writings supplemented with a few studies based on mitochondrial DNA. Here, we used genome-wide markers to m...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Heikkinen, M. E., Ruokonen, M., White, T. A., Alexander, M. M., Gündüz, I., Dobney, K. M., Aspi, J., Searle, J. B., Pyhäjärvi, T. Tags: Investigations Source Type: research
Measuring Genome Sizes Using Read-Depth, k-mers, and Flow Cytometry: Methodological Comparisons in Beetles (Coleoptera)
Measuring genome size across different species can yield important insights into evolution of the genome and allow for more informed decisions when designing next-generation genomic sequencing projects. New techniques for estimating genome size using shallow genomic sequence data have emerged which have the potential to augment our knowledge of genome sizes, yet these methods have only been used in a limited number of empirical studies. In this project, we compare estimation methods using next-generation sequencing (k-mer methods and average read depth of single-copy genes) to measurements from flow cytometry, a standard m...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Pflug, J. M., Holmes, V. R., Burrus, C., Johnston, J. S., Maddison, D. R. Tags: Investigations Source Type: research
rdmc: An Open Source R Package Implementing Convergent Adaptation Models of Lee and Coop (2017)
The availability of whole genome sequencing data from multiple related populations creates opportunities to test sophisticated population genetic models of convergent adaptation. Recent work by Lee and Coop (2017) developed models to infer modes of convergent adaption at local genomic scales, providing a rich framework for assessing how selection has acted across multiple populations at the tested locus. Here I present, rdmc, an R package that builds on the existing software implementation of Lee and Coop (2017) that prioritizes ease of use, portability, and scalability. I demonstrate installation and comprehensive overvie...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Tittes, S. Tags: Software and Data Resources Source Type: research
CeMbio - The Caenorhabditis elegans Microbiome Resource
The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic communities offer an effective approach to infer cause-effect relationships in host-microbiome systems. Yet the available communities suffer from several drawbacks, such as artificial (thus non-natural) choice of microbes, microbe-host mismatch (e.g., human microbes in gnotobiotic...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Dirksen, P., Assie, A., Zimmermann, J., Zhang, F., Tietje, A.-M., Marsh, S. A., Felix, M.-A., Shapira, M., Kaleta, C., Schulenburg, H., Samuel, B. S. Tags: Software and Data Resources Source Type: research
Ultraconserved Non-coding DNA Within Diptera and Hymenoptera
This study has taken advantage of the availability of the assembled genomic sequence of flies, mosquitos, ants and bees to explore the presence of ultraconserved sequence elements in these phylogenetic groups. We compared non-coding sequences found within and flanking Drosophila developmental genes to homologous sequences in Ceratitis capitata and Musca domestica. Many of the conserved sequence blocks (CSBs) that constitute Drosophila cis-regulatory DNA, recognized by EvoPrinter alignment protocols, are also conserved in Ceratitis and Musca. Also conserved is the position but not necessarily the orientation of many of thes...
Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Brody, T., Yavatkar, A., Kuzin, A., Odenwald, W. F. Tags: Software and Data Resources Source Type: research
