Evolution of Resistance Against CRISPR/Cas9 Gene Drive [Population and Evolutionary Genetics]
This study highlights the need for careful modeling of the population dynamics of CGD prior to the actual release of a driver construct into the wild. (Source: Genetics)
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Unckless, R. L., Clark, A. G., Messer, P. W. Tags: Population and Evolutionary Genetics Source Type: research
Selection Limits to Adaptive Walks on Correlated Landscapes [Population and Evolutionary Genetics]
Adaptation depends critically on the effects of new mutations and their dependency on the genetic background in which they occur. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Heredia, J. P., Trubenova, B., Sudholt, D., Paixao, T. Tags: Population and Evolutionary Genetics Source Type: research
The Effect of an Extreme and Prolonged Population Bottleneck on Patterns of Deleterious Variation: Insights from the Greenlandic Inuit [Population and Evolutionary Genetics]
The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit we show that the Inuit have undergone a severe ~20,000-year-long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population tested to date, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inui...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Pedersen, C.-E. T., Lohmueller, K. E., Grarup, N., Bjerregaard, P., Hansen, T., Siegismund, H. R., Moltke, I., Albrechtsen, A. Tags: Population and Evolutionary Genetics Source Type: research
Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans [Developmental and Behavioral Genetics]
Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited, despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent system to study this mechanism. We found, through genetic manipulation and lipid analysis, that biosynthesis of ceramide, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic interaction analysis suggests that ceramide may act in both insulin-IGF-1...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Cui, M., Wang, Y., Cavaleri, J., Kelson, T., Teng, Y., Han, M. Tags: Developmental and Behavioral Genetics Source Type: research
Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster [Developmental and Behavioral Genetics]
Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging’s functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {forBAC} rescue allele. We show that a total loss of foraging expression in larvae results ...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Allen, A. M., Anreiter, I., Neville, M. C., Sokolowski, M. B. Tags: Developmental and Behavioral Genetics Source Type: research
H2O2-Sensitive Isoforms of Drosophila melanogaster TRPA1 Act in Bitter-Sensing Gustatory Neurons to Promote Avoidance of UV During Egg-Laying [Developmental and Behavioral Genetics]
The evolutionarily conserved TRPA1 channel can sense various stimuli including temperatures and chemical irritants. Recent results have suggested that specific isoforms of Drosophila TRPA1 (dTRPA1) are UV-sensitive and that their UV sensitivity is due to H2O2 sensitivity. However, whether such UV sensitivity served any physiological purposes in animal behavior was unclear. Here, we demonstrate that H2O2-sensitive dTRPA1 isoforms promote avoidance of UV when adult Drosophila females are selecting sites for egg-laying. First, we show that blind/visionless females are still capable of sensing and avoiding UV during egg-laying...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Guntur, A. R., Gou, B., Gu, P., He, R., Stern, U., Xiang, Y., Yang, C.-H. Tags: Developmental and Behavioral Genetics Source Type: research
The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit [Developmental and Behavioral Genetics]
During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tum...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Josephson, M. P., Aliani, R., Norris, M. L., Ochs, M. E., Gujar, M., Lundquist, E. A. Tags: Developmental and Behavioral Genetics Source Type: research
A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B [Developmental and Behavioral Genetics]
Myosin 18B is an unconventional myosin that has been implicated in tumor progression in humans. In addition, loss-of-function mutations of the MYO18B gene have recently been identified in several patients exhibiting symptoms of nemaline myopathy. In mouse, mutation of Myo18B results in early developmental arrest associated with cardiomyopathy, precluding analysis of its effects on skeletal muscle development. The zebrafish, frozen (fro) mutant was identified as one of a group of immotile mutants in the 1996 Tübingen genetic screen. Mutant embryos display a loss of birefringency in their skeletal muscle, indicative of ...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Gurung, R., Ono, Y., Baxendale, S., Lee, S. L. C., Moore, S., Calvert, M., Ingham, P. W. Tags: Developmental and Behavioral Genetics Source Type: research
Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components [Developmental and Behavioral Genetics]
Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself a...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Şahin, A., Held, A., Bredvik, K., Major, P., Achilli, T.-M., Kerson, A. G., Wharton, K., Stilwell, G., Reenan, R. Tags: Developmental and Behavioral Genetics Source Type: research
Evidence for Amino Acid Snorkeling from a High-Resolution, In Vivo Analysis of Fis1 Tail-Anchor Insertion at the Mitochondrial Outer Membrane [Cellular Genetics]
Proteins localized to mitochondria by a carboxyl-terminal tail anchor (TA) play roles in apoptosis, mitochondrial dynamics, and mitochondrial protein import. To reveal characteristics of TAs that may be important for mitochondrial targeting, we focused our attention upon the TA of the Saccharomyces cerevisiae Fis1 protein. Specifically, we generated a library of Fis1p TA variants fused to the Gal4 transcription factor, then, using next-generation sequencing, revealed which Fis1p TA mutations inhibited membrane insertion and allowed Gal4p activity in the nucleus. Prompted by our global analysis, we subsequently analyzed the...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Keskin, A., Akdoğan, E., Dunn, C. D. Tags: Cellular Genetics Source Type: research
Traffic Through the Trans-Golgi Network and the Endosomal System Requires Collaboration Between Exomer and Clathrin Adaptors in Fission Yeast [Cellular Genetics]
Despite its biological and medical relevance, traffic from the Golgi to the plasma membrane (PM) is one of the least understood steps of secretion. Exomer is a protein complex that mediates the trafficking of certain cargoes from the trans-Golgi network/early endosomes to the PM in budding yeast. Here, we show that in Schizosaccharomyces pombe the Cfr1 and Bch1 proteins constitute the simplest form of an exomer. Cfr1 co-immunoprecipitates with Assembly Polypeptide adaptor 1 (AP-1), AP-2, and Golgi-localized, gamma-adaptin ear domain homology, ARF-binding (GGA) subunits, and cfr1+ interacts genetically with AP-1 and GGA gen...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Hoya, M., Yanguas, F., Moro, S., Prescianotto-Baschong, C., Doncel, C., de Leon, N., Curto, M.- A., Spang, A., Valdivieso, M.- H. Tags: Cellular Genetics Source Type: research
Meiotic Centromere Coupling and Pairing Function by Two Separate Mechanisms in Saccharomyces cerevisiae [Cellular Genetics]
In meiosis I, chromosomes become paired with their homologous partners and then are pulled toward opposite poles of the spindle. In the budding yeast, Saccharomyces cerevisiae, in early meiotic prophase, centromeres are observed to associate in pairs in a homology-independent manner; a process called centromere coupling. Later, as homologous chromosomes align, their centromeres associate in a process called centromere pairing. The synaptonemal complex protein Zip1 is necessary for both types of centromere association. We aimed to test the role of centromere coupling in modulating recombination at centromeres, and to test w...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Kurdzo, E. L., Obeso, D., Chuong, H., Dawson, D. S. Tags: Cellular Genetics Source Type: research
General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization [Gene Expression]
Nitrogen catabolite repression (NCR), the ability of Saccharomyces cerevisiae to use good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcription activators Gln3 and Gat1. In nitrogen-replete conditions, the GATA factors are cytoplasmic and NCR-sensitive transcription minimal. When only poor nitrogen sources are available, Gln3 is nuclear, dramatically increasing GATA factor-mediated transcription. This regulation was originally attributed to mechanistic Tor protein kinase complex 1 (mTorC1)-mediated control of Gln3. However, we recently showed that two regu...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Tate, J. J., Buford, D., Rai, R., Cooper, T. G. Tags: Gene Expression Source Type: research
Multiple Transcriptional and Post-transcriptional Pathways Collaborate to Control Sense and Antisense RNAs of Tf2 Retroelements in Fission Yeast [Gene Expression]
Retrotransposons are mobile genetic elements that colonize eukaryotic genomes by replicating through an RNA intermediate. As retrotransposons can move within the host genome, defense mechanisms have evolved to repress their potential mutagenic activities. In the fission yeast Schizosaccharomyces pombe, the mRNA of Tf2 long terminal repeat retrotransposons is targeted for degradation by the 3'–5' exonucleolytic activity of the exosome-associated protein Rrp6. Here, we show that the nuclear poly(A)-binding protein Pab2 functions with Rrp6 to negatively control Tf2 mRNA accumulation. Furthermore, we found that Pab2/Rrp6...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Mallet, P.-L., Larochelle, M., Bachand, F. Tags: Gene Expression Source Type: research
Stable Binding of the Conserved Transcription Factor Grainy Head to its Target Genes Throughout Drosophila melanogaster Development [Gene Expression]
It has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct ...
Source: Genetics - February 1, 2017 Category: Genetics & Stem Cells Authors: Nevil, M., Bondra, E. R., Schulz, K. N., Kaplan, T., Harrison, M. M. Tags: Gene Expression Source Type: research
