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  • Innate immune signaling in Drosophila shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis to support immune function
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-23
    Brittany A. Martínez; Rosalie G. Hoyle; Scott Yeudall; Mitchell E. Granade; Thurl E. Harris; J. David Castle; Norbert Leitinger; Michelle L. Bland

    During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize and kill invading pathogens. In Drosophila, these effectors are antimicrobial peptides (AMPs) that are produced in the fat body, an organ that also serves as a major lipid storage depot. Here we asked how activation of Toll signaling in the

    更新日期:2020-11-25
  • Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-23
    Yunpeng Wang; Ron Nudel; Michael E. Benros; Kristin Skogstrand; Simon Fishilevich; iPSYCH-BROAD; Doron Lancet; Jiangming Sun; David M. Hougaard; Ole A. Andreassen; Preben Bo Mortensen; Alfonso Buil; Thomas F. Hansen; Wesley K. Thompson; Thomas Werge

    Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic

    更新日期:2020-11-25
  • A phenome-wide association study of 26 mendelian genes reveals phenotypic expressivity of common and rare variants within the general population
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-23
    Catherine Tcheandjieu; Matthew Aguirre; Stefan Gustafsson; Priyanka Saha; Praneetha Potiny; Melissa Haendel; Erik Ingelsson; Manuel A. Rivas; James R. Priest

    The clinical evaluation of a genetic syndrome relies upon recognition of a characteristic pattern of signs or symptoms to guide targeted genetic testing for confirmation of the diagnosis. However, individuals displaying a single phenotype of a complex syndrome may not meet criteria for clinical diagnosis or genetic testing. Here, we present a phenome-wide association study (PheWAS) approach to systematically

    更新日期:2020-11-25
  • Rare genetic variation at transcription factor binding sites modulates local DNA methylation profiles
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-20
    Alejandro Martin-Trujillo; Nihir Patel; Felix Richter; Bharati Jadhav; Paras Garg; Sarah U. Morton; David M. McKean; Steven R. DePalma; Elizabeth Goldmuntz; Dorota Gruber; Richard Kim; Jane W. Newburger; George A. Porter Jr.; Alessandro Giardini; Daniel Bernstein; Martin Tristani-Firouzi; Jonathan G. Seidman; Christine E. Seidman; Wendy K. Chung; Bruce D. Gelb; Andrew J. Sharp

    Although DNA methylation is the best characterized epigenetic mark, the mechanism by which it is targeted to specific regions in the genome remains unclear. Recent studies have revealed that local DNA methylation profiles might be dictated by cis-regulatory DNA sequences that mainly operate via DNA-binding factors. Consistent with this finding, we have recently shown that disruption of CTCF-binding

    更新日期:2020-11-21
  • No association between SCN9A and monogenic human epilepsy disorders
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-20
    James Fasham; Joseph S. Leslie; Jamie W. Harrison; James Deline; Katie B. Williams; Ashley Kuhl; Jessica Scott Schwoerer; Harold E. Cross; Andrew H. Crosby; Emma L. Baple

    Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile

    更新日期:2020-11-21
  • Unique genetic signatures of local adaptation over space and time for diapause, an ecologically relevant complex trait, in Drosophila melanogaster
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-20
    Priscilla A. Erickson; Cory A. Weller; Daniel Y. Song; Alyssa S. Bangerter; Paul Schmidt; Alan O. Bergland

    Organisms living in seasonally variable environments utilize cues such as light and temperature to induce plastic responses, enabling them to exploit favorable seasons and avoid unfavorable ones. Local adapation can result in variation in seasonal responses, but the genetic basis and evolutionary history of this variation remains elusive. Many insects, including Drosophila melanogaster, are able to

    更新日期:2020-11-21
  • Mms19 promotes spindle microtubule assembly in Drosophila neural stem cells
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-19
    Rohan Chippalkatti; Boris Egger; Beat Suter

    Mitotic divisions depend on the timely assembly and proper orientation of the mitotic spindle. Malfunctioning of these processes can considerably delay mitosis, thereby compromising tissue growth and homeostasis, and leading to chromosomal instability. Loss of functional Mms19 drastically affects the growth and development of mitotic tissues in Drosophila larvae and we now demonstrate that Mms19 is

    更新日期:2020-11-21
  • Stability of SARS-CoV-2 phylogenies
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-18
    Yatish Turakhia; Nicola De Maio; Bryan Thornlow; Landen Gozashti; Robert Lanfear; Conor R. Walker; Angie S. Hinrichs; Jason D. Fernandes; Rui Borges; Greg Slodkowicz; Lukas Weilguny; David Haussler; Nick Goldman; Russell Corbett-Detig

    The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort

    更新日期:2020-11-19
  • The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-18
    Ana Martínez-Marchal; Yan Huang; Maria Teresa Guillot-Ferriols; Mònica Ferrer-Roda; Anna Guixé; Montserrat Garcia-Caldés; Ignasi Roig

    Mammalian oogonia proliferate without completing cytokinesis, forming cysts. Within these, oocytes differentiate and initiate meiosis, promoting double-strand break (DSBs) formation, which are repaired by homologous recombination (HR) causing the pairing and synapsis of the homologs. Errors in these processes activate checkpoint mechanisms, leading to apoptosis. At the end of prophase I, in contrast

    更新日期:2020-11-19
  • Multivariable G-E interplay in the prediction of educational achievement
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-17
    Andrea G. Allegrini; Ville Karhunen; Jonathan R. I. Coleman; Saskia Selzam; Kaili Rimfeld; Sophie von Stumm; Jean-Baptiste Pingault; Robert Plomin

    Polygenic scores are increasingly powerful predictors of educational achievement. It is unclear, however, how sets of polygenic scores, which partly capture environmental effects, perform jointly with sets of environmental measures, which are themselves heritable, in prediction models of educational achievement. Here, for the first time, we systematically investigate gene-environment correlation (rGE)

    更新日期:2020-11-17
  • Inhibition of the de novo pyrimidine biosynthesis pathway limits ribosomal RNA transcription causing nucleolar stress in glioblastoma cells
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-17
    M. Carmen Lafita-Navarro; Niranjan Venkateswaran; Jessica A. Kilgore; Suman Kanji; Jungsoo Han; Spencer Barnes; Noelle S. Williams; Michael Buszczak; Sandeep Burma; Maralice Conacci-Sorrell

    Glioblastoma is the most common and aggressive type of cancer in the brain; its poor prognosis is often marked by reoccurrence due to resistance to the chemotherapeutic agent temozolomide, which is triggered by an increase in the expression of DNA repair enzymes such as MGMT. The poor prognosis and limited therapeutic options led to studies targeted at understanding specific vulnerabilities of glioblastoma

    更新日期:2020-11-17
  • Identity-by-descent with uncertainty characterises connectivity of Plasmodium falciparum populations on the Colombian-Pacific coast
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-16
    Aimee R. Taylor; Diego F. Echeverry; Timothy J. C. Anderson; Daniel E. Neafsey; Caroline O. Buckee

    Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for. IBD-based

    更新日期:2020-11-17
  • Genotype imputation using the Positional Burrows Wheeler Transform
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-16
    Simone Rubinacci; Olivier Delaneau; Jonathan Marchini

    Genotype imputation is the process of predicting unobserved genotypes in a sample of individuals using a reference panel of haplotypes. In the last 10 years reference panels have increased in size by more than 100 fold. Increasing reference panel size improves accuracy of markers with low minor allele frequencies but poses ever increasing computational challenges for imputation methods. Here we present

    更新日期:2020-11-17
  • Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-13
    Li Chen; Xiaorong Gu; Xuetao Huang; Rui Liu; Jinxiu Li; Yiqing Hu; Guoqin Li; Tao Zeng; Yong Tian; Xiaoxiang Hu; Lizhi Lu; Ning Li

    Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G. Transcription factor

    更新日期:2020-11-15
  • New insights into the function of mammalian Argonaute2
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-12
    Marek Marzec

    Uncovering the mechanisms that recognise a microRNA (miRNA) target is 1 of the biggest challenges because the Ago–miRNA complex is able to overcome different derogations of complementarity when binding targets. However, the recently solved crystallographic structure of Argonaute2 (Ago2) and a high-throughput analysis that used repurposed sequencing techniques has brought us closer to achieving this

    更新日期:2020-11-13
  • Meiosis reveals the early steps in the evolution of a neo-XY sex chromosome pair in the African pygmy mouse Mus minutoides
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-12
    Ana Gil-Fernández; Paul A. Saunders; Marta Martín-Ruiz; Marta Ribagorda; Pablo López-Jiménez; Daniel L. Jeffries; María Teresa Parra; Alberto Viera; Julio S. Rufas; Nicolas Perrin; Frederic Veyrunes; Jesús Page

    Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are thought to have evolved through an addition-attrition cycle involving the addition of autosomal segments to sex chromosomes and their subsequent differentiation. The events that drive this process are difficult to investigate because sex

    更新日期:2020-11-13
  • Microutrophin expression in dystrophic mice displays myofiber type differences in therapeutic effects
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Glen B. Banks; Jeffrey S. Chamberlain; Guy L. Odom

    Gene therapy approaches for DMD using recombinant adeno-associated viral (rAAV) vectors to deliver miniaturized (or micro) dystrophin genes to striated muscles have shown significant progress. However, concerns remain about the potential for immune responses against dystrophin in some patients. Utrophin, a developmental paralogue of dystrophin, may provide a viable treatment option. Here we examine

    更新日期:2020-11-12
  • The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Gloria Gonzalez Curto; Audrey Der Vartanian; Youcef El-Mokhtar Frarma; Line Manceau; Lorenzo Baldi; Selene Prisco; Nabila Elarouci; Frédéric Causeret; Daniil Korenkov; Muriel Rigolet; Frédéric Aurade; Aurélien De Reynies; Vincent Contremoulins; Frédéric Relaix; Orestis Faklaris; James Briscoe; Pascale Gilardi-Hebenstreit; Vanessa Ribes

    The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason

    更新日期:2020-11-12
  • Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Zhexu Dong; Lei Dai; Yong Zhang; Chao Fang; Gang Shi; Ye Chen; Junshu Li; Qin Wang; Jiamei Fu; Yan Yu; Wenshuang Wang; Lin Cheng; Yi Liu; Yi Lin; Yuan Wang; Qingnan Wang; Huiling Wang; Hantao Zhang; Yujing Zhang; Xiaolan Su; Shuang Zhang; Feng Wang; Meng Qiu; Zongguang Zhou; Hongxin Deng

    Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation

    更新日期:2020-11-12
  • Dual use and selection of GmSWEET39 for oil and protein improvement in soybean
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Hengyou Zhang; Wolfgang Goettel; Qijian Song; He Jiang; Zhenbin Hu; Ming Li Wang; Yong-qiang Charles An

    Soybean [Glycine max (L.) Merr.] was domesticated from wild soybean (G. soja Sieb. and Zucc.) and has been further improved as a dual-use seed crop to provide highly valuable oil and protein for food, feed, and industrial applications. However, the underlying genetic and molecular basis remains less understood. Having combined high-confidence bi-parental linkage mapping with high-resolution association

    更新日期:2020-11-12
  • LabWAS: Novel findings and study design recommendations from a meta-analysis of clinical labs in two independent biobanks
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Jeffery A. Goldstein; Joshua S. Weinstock; Lisa A. Bastarache; Daniel B. Larach; Lars G. Fritsche; Ellen M. Schmidt; Chad M. Brummett; Sachin Kheterpal; Goncalo R. Abecasis; Joshua C. Denny; Matthew Zawistowski

    Phenotypes extracted from Electronic Health Records (EHRs) are increasingly prevalent in genetic studies. EHRs contain hundreds of distinct clinical laboratory test results, providing a trove of health data beyond diagnoses. Such lab data is complex and lacks a ubiquitous coding scheme, making it more challenging than diagnosis data. Here we describe the first large-scale cross-health system genome-wide

    更新日期:2020-11-12
  • Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Kathryn S. Evans; Stefan Zdraljevic; Lewis Stevens; Kimberly Collins; Robyn E. Tanny; Erik C. Andersen

    Zinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required for cellular growth and development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to cell death. To avoid such fates, cells have evolved mechanisms to handle both an excess and a deficiency of zinc. Zinc homeostasis is largely maintained

    更新日期:2020-11-12
  • Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-11
    Aya Sato-Carlton; Chihiro Nakamura-Tabuchi; Xuan Li; Hendrik Boog; Madison K. Lehmer; Scott C. Rosenberg; Consuelo Barroso; Enrique Martinez-Perez; Kevin D. Corbett; Peter Mark Carlton

    In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found

    更新日期:2020-11-12
  • A novel role for kynurenine 3-monooxygenase in mitochondrial dynamics
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-10
    Daniel C. Maddison; Mónica Alfonso-Núñez; Aisha M. Swaih; Carlo Breda; Susanna Campesan; Natalie Allcock; Anna Straatman-Iwanowska; Charalambos P. Kyriacou; Flaviano Giorgini

    The enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. As the KP has been implicated in the pathogenesis of several human diseases, KMO and other enzymes that control metabolic flux through the pathway are potential therapeutic targets for these disorders. While KMO is localized to the outer mitochondrial

    更新日期:2020-11-12
  • A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-09
    Benjamin L. S. Furman; Caroline M. S. Cauret; Martin Knytl; Xue-Ying Song; Tharindu Premachandra; Caleb Ofori-Boateng; Danielle C. Jordan; Marko E. Horb; Ben J. Evans

    In many species, sexual differentiation is a vital prelude to reproduction, and disruption of this process can have severe fitness effects, including sterility. It is thus interesting that genetic systems governing sexual differentiation vary among—and even within—species. To understand these systems more, we investigated a rare example of a frog with three sex chromosomes: the Western clawed frog

    更新日期:2020-11-12
  • The Bric-à-Brac BTB/POZ transcription factors are necessary in niche cells for germline stem cells establishment and homeostasis through control of BMP/DPP signaling in the Drosophila melanogaster ovary
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-05
    Laurine Miscopein Saler; Virginie Hauser; Mathieu Bartoletti; Charlotte Mallart; Marianne Malartre; Laura Lebrun; Anne-Marie Pret; Laurent Théodore; Fabienne Chalvet; Sophie Netter

    Many studies have focused on the mechanisms of stem cell maintenance via their interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. Adult Drosophila melanogaster ovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack

    更新日期:2020-11-05
  • A complementary study approach unravels novel players in the pathoetiology of Hirschsprung disease
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-05
    Tanja Mederer; Stefanie Schmitteckert; Julia Volz; Cristina Martínez; Ralph Röth; Thomas Thumberger; Volker Eckstein; Jutta Scheuerer; Cornelia Thöni; Felix Lasitschka; Leonie Carstensen; Patrick Günther; Stefan Holland-Cunz; Robert Hofstra; Erwin Brosens; Jill A. Rosenfeld; Christian P. Schaaf; Duco Schriemer; Isabella Ceccherini; Marta Rusmini; Joseph Tilghman; Berta Luzón-Toro; Ana Torroglosa; Salud

    Hirschsprung disease (HSCR, OMIM 142623) involves congenital intestinal obstruction caused by dysfunction of neural crest cells and their progeny during enteric nervous system (ENS) development. HSCR is a multifactorial disorder; pathogenetic variants accounting for disease phenotype are identified only in a minority of cases, and the identification of novel disease-relevant genes remains challenging

    更新日期:2020-11-05
  • The RSC (Remodels the Structure of Chromatin) complex of Candida albicans shows compositional divergence with distinct roles in regulating pathogenic traits
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-05
    Vinutha K. Balachandra; Jiyoti Verma; Madhu Shankar; Timothy M. Tucey; Ana Traven; Ralf B. Schittenhelm; Santanu K. Ghosh

    Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members

    更新日期:2020-11-05
  • A genetic variant controls interferon-β gene expression in human myeloid cells by preventing C/EBP-β binding on a conserved enhancer
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-04
    Anaïs Assouvie; Maxime Rotival; Juliette Hamroune; Didier Busso; Paul-Henri Romeo; Lluis Quintana-Murci; Germain Rousselet

    Interferon β (IFN-β) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells

    更新日期:2020-11-05
  • Loss of hepatocyte cell division leads to liver inflammation and fibrosis
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-04
    Matthew R. Dewhurst; Jin Rong Ow; Gözde Zafer; Noémi K. M. van Hul; Heike Wollmann; Xavier Bisteau; David Brough; Hyungwon Choi; Philipp Kaldis

    The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate whether blocking hepatocyte division using two different mouse models affects physiology

    更新日期:2020-11-05
  • A C. elegans Zona Pellucida domain protein functions via its ZPc domain
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-03
    Jennifer D. Cohen; Jessica G. Bermudez; Matthew C. Good; Meera V. Sundaram

    Zona Pellucida domain (ZP) proteins are critical components of the body’s external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model

    更新日期:2020-11-04
  • Mutations in PIH proteins MOT48, TWI1 and PF13 define common and unique steps for preassembly of each, different ciliary dynein
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-03
    Ryosuke Yamamoto; Shiho Yanagi; Masahito Nagao; Yuya Yamasaki; Yui Tanaka; Winfield S. Sale; Toshiki Yagi; Takahide Kon

    Ciliary dyneins are preassembled in the cytoplasm before being transported into cilia, and a family of proteins containing the PIH1 domain, PIH proteins, are involved in the assembly process. However, the functional differences and relationships between members of this family of proteins remain largely unknown. Using Chlamydomonas reinhardtii as a model, we isolated and characterized two novel Chlamydomonas

    更新日期:2020-11-04
  • A spectrum of verticality across genes
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Falk S. P. Nagies; Julia Brueckner; Fernando D. K. Tria; William F. Martin

    Lateral gene transfer (LGT) has impacted prokaryotic genome evolution, yet the extent to which LGT compromises vertical evolution across individual genes and individual phyla is unknown, as are the factors that govern LGT frequency across genes. Estimating LGT frequency from tree comparisons is problematic when thousands of genomes are compared, because LGT becomes difficult to distinguish from phylogenetic

    更新日期:2020-11-03
  • Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Audrey Gerstel; Jordi Zamarreño Beas; Yohann Duverger; Emmanuelle Bouveret; Frédéric Barras; Béatrice Py

    The level of antibiotic resistance exhibited by bacteria can vary as a function of environmental conditions. Here, we report that phenazine-methosulfate (PMS), a redox-cycling compound (RCC) enhances resistance to fluoroquinolone (FQ) norfloxacin. Genetic analysis showed that E. coli adapts to PMS stress by making Fe-S clusters with the SUF machinery instead of the ISC one. Based upon phenotypic analysis

    更新日期:2020-11-03
  • NIGT1 family proteins exhibit dual mode DNA recognition to regulate nutrient response-associated genes in Arabidopsis
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Yoshiaki Ueda; Shohei Nosaki; Yasuhito Sakuraba; Takuya Miyakawa; Takatoshi Kiba; Masaru Tanokura; Shuichi Yanagisawa

    Fine-tuning of nutrient uptake and response is indispensable for maintenance of nutrient homeostasis in plants, but the details of underlying mechanisms remain to be elucidated. NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1 (NIGT1) family proteins are plant-specific transcriptional repressors that function as an important hub in the nutrient signaling network associated with the acquisition

    更新日期:2020-11-03
  • TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Emese Pataki; LubFtablea Simhaev; Hamutal Engel; Adiel Cohen; Martin Kupiec; Ronit Weisman

    The Target of rapamycin (TOR) protein kinase forms part of TOR complex 1 (TORC1) and TOR complex 2 (TORC2), two multi-subunit protein complexes that regulate growth, proliferation, survival and developmental processes by phosphorylation and activation of AGC-family kinases. In the fission yeast, Schizosaccharomyces pombe, TORC2 and its target, the AGC kinase Gad8 (an orthologue of human AKT or SGK1)

    更新日期:2020-11-03
  • Gtsf1 is essential for proper female sex determination and transposon silencing in the silkworm, Bombyx mori
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Kai Chen; Ye Yu; Dehong Yang; Xu Yang; Linmeng Tang; Yujia Liu; Xingyu Luo; James R. Walter; Zulian Liu; Jun Xu; Yongping Huang

    Sex determination pathways are astoundingly diverse in insects. For instance, the silk moth Bombyx mori uniquely use various components of the piRNA pathway to produce the Fem signal for specification of the female fate. In this study, we identified BmGTSF1 as a novel piRNA factor which participates in B. mori sex determination. We found that BmGtsf1 has a distinct expression pattern compared to Drosophila

    更新日期:2020-11-03
  • Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Lene Clausen; Amelie Stein; Martin Grønbæk-Thygesen; Lasse Nygaard; Cecilie L. Søltoft; Sofie V. Nielsen; Michael Lisby; Tommer Ravid; Kresten Lindorff-Larsen; Rasmus Hartmann-Petersen

    Germline mutations in the folliculin (FLCN) tumor suppressor gene are linked to Birt-Hogg-Dubé (BHD) syndrome, a dominantly inherited genetic disease characterized by predisposition to fibrofolliculomas, lung cysts, and renal cancer. Most BHD-linked FLCN variants include large deletions and splice site aberrations predicted to cause loss of function. The mechanisms by which missense variants and short

    更新日期:2020-11-03
  • Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearum
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Hang Jiang; Aliang Xia; Meng Ye; Jingyi Ren; Dongao Li; Huiquan Liu; Qinhu Wang; Ping Lu; Chunlan Wu; Jin-Rong Xu; Cong Jiang

    Histone acetylation, balanced by histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes, affects dynamic transitions of chromatin structure to regulate transcriptional accessibility. However, little is known about the interplay between HAT and HDAC complexes in Fusarium graminearum, a causal agent of Fusarium Head Blight (FHB) that uniquely contains chromosomal regions enriched for

    更新日期:2020-11-03
  • Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Damien Garrido; Mohammed Bourouh; Éric Bonneil; Pierre Thibault; Andrew Swan; Vincent Archambault

    In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its co-activator Cdc20. The identity of the kinase(s) responsible for APC/C

    更新日期:2020-11-03
  • The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Franck Chesnel; Anne Couturier; Adrien Alusse; Jean-Philippe Gagné; Guy G. Poirier; Dominique Jean; François-Michel Boisvert; Pauline Hascoet; Luc Paillard; Yannick Arlot-Bonnemains; Xavier Le Goff

    Loss of von Hippel-Lindau protein pVHL function promotes VHL diseases, including sporadic and inherited clear cell Renal Cell Carcinoma (ccRCC). Mechanisms controlling pVHL function and regulation, including folding and stability, remain elusive. Here, we have identified the conserved cochaperone prefoldin complex in a screen for pVHL interactors. The prefoldin complex delivers non-native proteins

    更新日期:2020-11-03
  • Differential transcript usage in the Parkinson’s disease brain
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Fiona Dick; Gonzalo S. Nido; Guido Werner Alves; Ole-Bjørn Tysnes; Gry Hilde Nilsen; Christian Dölle; Charalampos Tzoulis

    Studies of differential gene expression have identified several molecular signatures and pathways associated with Parkinson’s disease (PD). The role of isoform switches and differential transcript usage (DTU) remains, however, unexplored. Here, we report the first genome-wide study of DTU in PD. We performed RNA sequencing following ribosomal RNA depletion in prefrontal cortex samples of 49 individuals

    更新日期:2020-11-03
  • Genetic engineering of sex chromosomes for batch cultivation of non-transgenic, sex-sorted males
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Siba R. Das; Maciej Maselko; Ambuj Upadhyay; Michael J. Smanski

    The field performance of Sterile Insect Technique (SIT) is improved by sex-sorting and releasing only sterile males. This can be accomplished by resource-intensive separation of males from females by morphology. Alternatively, sex-ratio biasing genetic constructs can be used to selectively remove one sex without the need for manual or automated sorting, but the resulting genetically engineered (GE)

    更新日期:2020-11-03
  • Dual genome-wide CRISPR knockout and CRISPR activation screens identify mechanisms that regulate the resistance to multiple ATR inhibitors
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Emily M. Schleicher; Ashna Dhoonmoon; Lindsey M. Jackson; Kristen E. Clements; Coryn L. Stump; Claudia M. Nicolae; George-Lucian Moldovan

    The ataxia telangiectasia and Rad3-related (ATR) protein kinase is a key regulator of the cellular response to DNA damage. Due to increased amount of replication stress, cancer cells heavily rely on ATR to complete DNA replication and cell cycle progression. Thus, ATR inhibition is an emerging target in cancer therapy, with multiple ATR inhibitors currently undergoing clinical trials. Here, we describe

    更新日期:2020-11-03
  • Suppression of retinal degeneration by two novel ERAD ubiquitin E3 ligases SORDD1/2 in Drosophila
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Jaiwei Xu; Haifang Zhao; Tao Wang

    Mutations in the gene rhodopsin are one of the major causes of autosomal dominant retinitis pigmentosa (adRP). Mutant forms of Rhodopsin frequently accumulate in the endoplasmic reticulum (ER), cause ER stress, and trigger photoreceptor cell degeneration. Here, we performed a genome-wide screen to identify suppressors of retinal degeneration in a Drosophila model of adRP, carrying a point mutation

    更新日期:2020-11-03
  • In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Hui Hong; Shun Yao; Yuanyuan Zhang; Yi Ye; Cheng Li; Liang Hu; Yihua Sun; Hsin-Yi Huang; Hongbin Ji

    MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human

    更新日期:2020-11-03
  • A pair of ascending neurons in the subesophageal zone mediates aversive sensory inputs-evoked backward locomotion in Drosophila larvae
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Natsuko Omamiuda-Ishikawa; Moeka Sakai; Kazuo Emoto

    Animals typically avoid unwanted situations with stereotyped escape behavior. For instance, Drosophila larvae often escape from aversive stimuli to the head, such as mechanical stimuli and blue light irradiation, by backward locomotion. Responses to these aversive stimuli are mediated by a variety of sensory neurons including mechanosensory class III da (C3da) sensory neurons and blue-light responsive

    更新日期:2020-11-03
  • Inferring causal direction between two traits in the presence of horizontal pleiotropy with GWAS summary data
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Haoran Xue; Wei Pan

    Orienting the causal relationship between pairs of traits is a fundamental task in scientific research with significant implications in practice, such as in prioritizing molecular targets and modifiable risk factors for developing therapeutic and interventional strategies for complex diseases. A recent method, called Steiger’s method, using a single SNP as an instrument variable (IV) in the framework

    更新日期:2020-11-03
  • A proteomic survey of microtubule-associated proteins in a R402H TUBA1A mutant mouse
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Ines Leca; Alexander Phillips; Iris Hofer; Lukas Landler; Lyubov Ushakova; Thomas David Cushion; Gerhard Dürnberger; Karel Stejskal; Karl Mechtler; David Anthony Keays

    Microtubules play a critical role in multiple aspects of neurodevelopment, including the generation, migration and differentiation of neurons. A recurrent mutation (R402H) in the α-tubulin gene TUBA1A is known to cause lissencephaly with cerebellar and striatal phenotypes. Previous work has shown that this mutation does not perturb the chaperone-mediated folding of tubulin heterodimers, which are able

    更新日期:2020-11-03
  • Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency
    PLOS Genet. (IF 5.174) Pub Date : 2020-11-02
    Federica Diofano; Karolina Weinmann; Isabelle Schneider; Kevin D. Thiessen; Wolfgang Rottbauer; Steffen Just

    Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found

    更新日期:2020-11-03
  • CenH3 distribution reveals extended centromeres in the model beetle Tribolium castaneum
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-30
    Tena Gržan; Evelin Despot-Slade; Nevenka Meštrović; Miroslav Plohl; Brankica Mravinac

    Centromeres are chromosomal domains essential for kinetochore assembly and correct chromosome segregation. Inconsistent in their underlying DNA sequences, centromeres are defined epigenetically by the presence of the centromere-specific histone H3 variant CenH3. Most of the analyzed eukaryotes have monocentric chromosomes in which CenH3 proteins deposit into a single, primary constriction visible at

    更新日期:2020-11-02
  • DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-30
    Alexandre Duprey; Eduardo A. Groisman

    DNA supercoiling is essential for all living cells because it controls all processes involving DNA. In bacteria, global DNA supercoiling results from the opposing activities of topoisomerase I, which relaxes DNA, and DNA gyrase, which compacts DNA. These enzymes are widely conserved, sharing >91% amino acid identity between the closely related species Escherichia coli and Salmonella enterica serovar

    更新日期:2020-11-02
  • Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-30
    Brendan Evano; Diljeet Gill; Irene Hernando-Herraez; Glenda Comai; Thomas M. Stubbs; Pierre-Henri Commere; Wolf Reik; Shahragim Tajbakhsh

    Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants

    更新日期:2020-11-02
  • Evolution of linkage and genome expansion in protocells: The origin of chromosomes
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-29
    András Szilágyi; Viktor Péter Kovács; Eörs Szathmáry; Mauro Santos

    Chromosomes are likely to have assembled from unlinked genes in early evolution. Genetic linkage reduces the assortment load and intragenomic conflict in reproducing protocell models to the extent that chromosomes can go to fixation even if chromosomes suffer from a replicative disadvantage, relative to unlinked genes, proportional to their length. Here we numerically show that chromosomes spread within

    更新日期:2020-10-30
  • Extensive trimming of short single-stranded DNA oligonucleotides during replication-coupled gene editing in mammalian cells
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-29
    Thomas W. van Ravesteyn; Marcos Arranz Dols; Wietske Pieters; Marleen Dekker; Hein te Riele

    Through transfection of short single-stranded oligodeoxyribonucleotides (ssODNs) small genomic alterations can be introduced into mammalian cells with high precision. ssODNs integrate into the genome during DNA replication, but the resulting heteroduplex is prone to detection by DNA mismatch repair (MMR), which prevents effective gene modification. We have previously demonstrated that the suppressive

    更新日期:2020-10-30
  • Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-28
    Koji Ishikawa; Akari Ishihara; Hisao Moriya

    Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables

    更新日期:2020-10-30
  • Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-28
    Marco Galardini; Olivier Clermont; Alexandra Baron; Bede Busby; Sara Dion; Sören Schubert; Pedro Beltrao; Erick Denamur

    The genus Escherichia is composed of several species and cryptic clades, including E. coli, which behaves as a vertebrate gut commensal, but also as an opportunistic pathogen involved in both diarrheic and extra-intestinal diseases. To characterize the genetic determinants of extra-intestinal virulence within the genus, we carried out an unbiased genome-wide association study (GWAS) on 370 commensal

    更新日期:2020-10-30
  • Developmental constraint shaped genome evolution and erythrocyte loss in Antarctic fishes following paleoclimate change
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-27
    Jacob M. Daane; Juliette Auvinet; Alicia Stoebenau; Donald Yergeau; Matthew P. Harris; H. William Detrich III

    In the frigid, oxygen-rich Southern Ocean (SO), Antarctic icefishes (Channichthyidae; Notothenioidei) evolved the ability to survive without producing erythrocytes and hemoglobin, the oxygen-transport system of virtually all vertebrates. Here, we integrate paleoclimate records with an extensive phylogenomic dataset of notothenioid fishes to understand the evolution of trait loss associated with climate

    更新日期:2020-10-30
  • Auxin apical dominance governed by the OsAsp1-OsTIF1 complex determines distinctive rice caryopses development on different branches
    PLOS Genet. (IF 5.174) Pub Date : 2020-10-27
    Shu Chang; Yixing Chen; Shenghua Jia; Yihao Li; Kun Liu; Zhouhua Lin; Hanmeng Wang; Zhilin Chu; Jin Liu; Chao Xi; Heping Zhao; Shengcheng Han; Yingdian Wang

    In rice (Oryza sativa), caryopses located on proximal secondary branches (CSBs) have smaller grain size and poorer grain filling than those located on apical primary branches (CPBs), greatly limiting grain yield. However, the molecular mechanism responsible for developmental differences between CPBs and CSBs remains elusive. In this transcriptome-wide expression study, we identified the gene Aspartic

    更新日期:2020-10-30