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Meghan Horne, Kaitlyn Krebushevski, Amelia Wells, Nahel Tunio, Casey Jarvis, Glen Francisco, Jane Geiss, Andrew Recknagel, David L Deitcher
Epilepsy is a neural disorder characterized by recurrent seizures. Bang-sensitive Drosophila represent an important model for studying epilepsy and neuronal excitability. Previous work identified the bang-sensitive gene slamdance (sda) as an allele of the aminopeptidase N gene. Here we show through extensive genetic analysis, including recombination frequency, deficiency mapping, transposon insertion complementation testing, RNA interference, and genetic rescue that the gene responsible for the seizure-sensitivity is julius seizure (jus), formerly CG14509, which encodes a novel transmembrane domain protein...
January 11, 2017: Genetics
Kristina Wehr Mathews, Margrith Cavegn, Monica Zwicky
Drosophila females are larger than males. In this paper, we describe how X chromosome dosage drives sexual dimorphism of body size through two means: first, through unbalanced expression of a key X-linked growth regulating gene and second, through female-specific activation of the sex-determination pathway. X-chromosome dosage determines phenotypic sex by regulating the genes of the sex-determining pathway. In the presence of two sets of X-chromosome signal elements (XSEs), Sex-lethal (Sxl) is activated in female (XX) but not male (XY) animals...
January 6, 2017: Genetics
David F McCleary, Jasper Rine
Calorie restriction extends lifespan in organisms as diverse as yeast and mammals through incompletely understood mechanism(s). The role of NAD(+)-dependent deacetylases, known as Sirtuins, in this process, particularly in the yeast S. cerevisiae is controversial. We measured chronological lifespan of wild-type and sir2Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2Δ extended lifespan in high-glucose complete minimal medium, and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie restriction response under these conditions...
January 6, 2017: Genetics
Clémentine Lasne, Carla M Sgrò, Tim Connallon
Models of sex chromosome and autosome evolution yield key predictions about the genomic basis of adaptive divergence, and such models have been important in guiding empirical research in comparative genomics and studies of speciation. In addition to the adaptive differentiation that occurs between species over time, selection also favors genetic divergence across geographic space, with subpopulations of single species evolving conspicuous differences in traits involved in adaptation to local environmental conditions...
January 6, 2017: Genetics
Guolian Kang, Wenjian Bi, Hang Zhang, Stanley Pounds, Cheng Cheng, Sanjay Shete, Fei Zou, Yanlong Zhao, Ji-Feng Zhang, Weihua Yue
In many case-control designs of genome-wide association (GWAS) or next generation sequencing (NGS) studies, extensive data on secondary traits that may correlate and share the common genetic variants with the primary disease are available. Investigating these secondary traits can provide critical insights into the disease etiology or pathology and enhance the GWAS or NGS results. Methods based on logistic regression (LG) were developed for this purpose. However, for the identification of rare variants (RVs), certain inadequacies in the LG models and algorithmic instability can cause severely inflated type I error and significant loss of power when the two traits are correlated and the RV is associated with the disease, especially at stringent significance levels...
December 30, 2016: Genetics
Chiara Merigliano, Antonio Marzio, Fioranna Renda, Maria Patrizia Somma, Maurizio Gatti, Fiammetta Vernì
The protein phosphatase 2A (PP2A) is a conserved heterotrimeric enzyme that regulates several cellular processes including the DNA damage response and mitosis. Consistent with these functions, PP2A is mutated in many types of cancer and acts as a tumor suppressor. In mammalian cells, PP2A inhibition results in DNA double strand breaks (DSBs) and chromosome aberrations (CABs). However, the mechanisms through which PP2A prevents DNA damage are still unclear. Here, we focus on the role of the Drosophila twins (tws) gene in the maintenance of chromosome integrity; tws encodes the B regulatory subunit (B/B55) of PP2A...
December 30, 2016: Genetics
Fengzhi Jin, Michael Bokros, Yanchang Wang
The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment that applies tension on kinetochores. Our previous data in budding yeast Saccharomyces cerevisiae show that Ipl1/Aurora B kinase and a centromere-associated protein Sgo1 are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete...
December 30, 2016: Genetics
NaTasha R Schiller, Christopher D Duchesneau, Latrisha S Lane, April R Reedy, Emily R Manzon, Pamela E Hoppe
We study the mechanisms that guide the formation and maintenance of the highly-ordered actin-myosin cytoskeleton in striated muscle. The UNC-82 kinase of Caenorhabditis elegans is orthologous to mammalian kinases ARK5/NUAK1 and SNARK/NUAK2. UNC-82 localizes to the M-line and is required for proper organization of thick filaments, but its substrate and mechanism of action are unknown. Antibody staining of three mutants with missense mutations in the UNC-82 catalytic domain revealed muscle structure that is less disorganized than in the null unc-82(0), but which contained distinctive ectopic accumulations not found in unc-82(0) These accumulations contain paramyosin and myosin B, but lack myosin A and myosin A-associated proteins as well as proteins of the integrin-associated complex...
December 30, 2016: Genetics
Pu Pu, Craig E Stone, Joshua T Burdick, John I Murray, Meera V Sundaram
Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the C. elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow, unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation...
December 30, 2016: Genetics
Aaron M Allen, Ina Anreiter, Megan C Neville, Marla B Sokolowski
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 for(0) null allele, and used recombineering to re-integrate a full copy of the gene, generating the {for(BAC)} rescue allele...
December 22, 2016: Genetics
Jennifer J Tate, David Buford, Rajendra Rai, Terrance G Cooper
Nitrogen Catabolite Repression (NCR), the ability of Saccharomyces cerevisiae to utilize good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcrip-tion 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 in-creasing GATA factor-mediated transcription. This regulation was originally attributed to mTorC1-mediated control of Gln3...
December 22, 2016: Genetics
Pierre-Luc Mallet, Marc Larochelle, François Bachand
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...
December 22, 2016: Genetics
Markus Nevil, Eliana R Bondra, Katharine N Schulz, Tommy Kaplan, Melissa M Harrison
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 is conserved from fungi to humans and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head gene, provide an excellent system to study this conserved factor...
December 22, 2016: Genetics
Mingzhi Lin, Edo Kussell
Inferring the rate of homologous recombination within a bacterial population remains a key challenge in quantifying the basic parameters of bacterial evolution. Due to the high sequence similarity within a clonal population, and unique aspects of bacterial DNA transfer processes, detecting recombination events based on phylogenetic reconstruction is often difficult, and estimating recombination rates using coalescent model-based methods is computationally expensive and often infeasible for large sequencing data sets...
December 22, 2016: Genetics
Fabienne Cleard, Daniel Wolle, Andrew M Taverner, Tsutomu Aoki, Girish Deshpande, Peter Andolfatto, Francois Karch, Paul Schedl
Chromatin boundary elements subdivide chromosomes in multicellular organisms into physically independent domains. In addition to this architectural function, these elements also play a critical role in gene regulation. Here we have investigated the evolution of a Drosophila Bithorax complex boundary element called Fab-7 which is required for the proper parasegment specific expression of the homeotic Abd-B gene. Using a "gene" replacement strategy, we show that Fab-7 boundaries from two closely related species D...
December 22, 2016: Genetics
Timothy G Vaughan, David Welch, Alexei J Drummond, Patrick J Biggs, Tessy George, Nigel P French
Homologous recombination is a central feature of bacterial evolution, yet confounds traditional phylogenetic methods. While a number of methods specific to bacterial evolution have been developed, none of these permit joint inference of a bacterial recombination graph and associated parameters. In this paper, we present a new method which addresses this shortcoming. Our method uses a novel Markov chain Monte Carlo algorithm to perform phylogenetic inference under the ClonalOrigin model of Didelot et al. (Genetics, 2010)...
December 22, 2016: Genetics
Philippa C Griffin, Sandra B Hangartner, Alexandre Fournier-Level, Ary A Hoffmann
Adaptation to environmental stress is critical for long-term species persistence. With climate change and other anthropogenic stressors compounding natural selective pressures, understanding the nature of adaptation is as important as ever in evolutionary biology. In particular, the number of alternative molecular trajectories available for an organism to reach the same adaptive phenotype remains poorly understood. Here we investigate this issue in a set of replicated Drosophila melanogaster lines selected for increased desiccation resistance, a classical physiological trait that has been closely linked to Drosophila species distributions...
December 22, 2016: Genetics
Abdurrahman Keskin, Emel Akdoğan, Cory D Dunn
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...
December 22, 2016: Genetics
Adrian J McNairn, Vera D Rinaldi, John C Schimenti
The mammalian Mcm-domain containing 2 (Mcmdc2) gene encodes a protein of unknown function that is homologous to the mini-chromosome maintenance family of DNA replication licensing and helicase factors. Drosophila melanogaster contains two separate genes, the "Mei-MCMs," that appear to have arisen from a single ancestral Mcmdc2 gene. The Mei-MCMs are involved in promoting meiotic crossovers by blocking the anti-crossover activity of BLM helicase, a function presumably performed by MSH4 and MSH5 in metazoans...
December 16, 2016: Genetics
Hao Chen, Yanyan Tang, Jianfeng Liu, Lubin Tan, Jiahuang Jiang, Mumu Wang, Zuofeng Zhu, Xianyou Sun, Chuanqing Sun
Grain number is an important factor in determining grain production of rice (Oryza sativa L.). The molecular genetic basis for grain number is complex. Discovering new genes involved in regulating rice grain number increases our knowledge regarding its molecular mechanisms and aids breeding programs. Here, we identified GRAINS NUMBER 2 (GN2), a novel gene that is responsible for rice grain number, from 'Yuanjiang' common wild rice (Oryza rufipogon Griff.). Transgenic plants over-expressing GN2 showed less grain number, reduced plant height, and later heading date than control plants...
December 16, 2016: Genetics
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