scholarly journals The landscape of coadaptation in Vibrio parahaemolyticus

2018 ◽  
Author(s):  
Yujun Cui ◽  
Chao Yang ◽  
Hongling Qiu ◽  
Hui Wang ◽  
Ruifu Yang ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Vibrio Parahaemolyticus ◽  
Natural Populations ◽  
Bacterial Pathogen ◽  
Ecological Strategies ◽  
Bacterial Growth Rate ◽  
Cell Wall Biogenesis ◽  
Genome Wide ◽  
A Genome

AbstractInvestigating fitness interactions in natural populations remains a considerable challenge. We take advantage of the unique population structure of Vibrio parahaemolyticus, a bacterial pathogen of humans and shrimp, to perform a genome-wide screen for coadapted genetic elements. We identified 90 interaction groups involving 1,560 coding genes. 82 of these interaction groups are between accessory genes, many of which have functions related to carbohydrate transport and metabolism. Only 8 interaction groups involve both core and accessory genomes. The largest includes 1,540 SNPs in 82 genes and 338 accessory genome elements, many involved in lateral flagella and cell wall biogenesis. The interactions have a complex hierarchical structure encoding at least four distinct ecological strategies. Preliminary experiments imply that the strategies influence biofilm formation and bacterial growth rate in vitro. One strategy involves a divergent profile in multiple genome regions, implying that strains have irreversibly specialized, while the others involve fewer genes and are more plastic. Our results imply that most genetic alliances are ephemeral but that increasingly complex strategies can evolve and eventually cause speciation.

scholarly journals The landscape of coadaptation in Vibrio parahaemolyticus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yujun Cui ◽  
Chao Yang ◽  
Hongling Qiu ◽  
Hui Wang ◽  
Ruifu Yang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Population Structure ◽  
Vibrio Parahaemolyticus ◽  
Natural Populations ◽  
Bacterial Pathogen ◽  
Ecological Strategies ◽  
Cell Wall Biogenesis ◽  
Genome Wide ◽  
A Genome ◽  
Carbohydrate Transport

Investigating fitness interactions in natural populations remains a considerable challenge. We take advantage of the unique population structure of Vibrio parahaemolyticus, a bacterial pathogen of humans and shrimp, to perform a genome-wide screen for coadapted genetic elements. We identified 90 interaction groups (IGs) involving 1,560 coding genes. 82 IGs are between accessory genes, many of which have functions related to carbohydrate transport and metabolism. Only 8 involve both core and accessory genomes. The largest includes 1,540 SNPs in 82 genes and 338 accessory genome elements, many involved in lateral flagella and cell wall biogenesis. The interactions have a complex hierarchical structure encoding at least four distinct ecological strategies. One strategy involves a divergent profile in multiple genome regions, while the others involve fewer genes and are more plastic. Our results imply that most genetic alliances are ephemeral but that increasingly complex strategies can evolve and eventually cause speciation.

scholarly journals Genome-wide screen for genes involved in eDNA release during biofilm formation byStaphylococcus aureus

2017 ◽  
Vol 114 (29) ◽  
pp. E5969-E5978 ◽  
Author(s):  
Alicia S. DeFrancesco ◽  
Nadezda Masloboeva ◽  
Adnan K. Syed ◽  
Aaron DeLoughery ◽  
Niels Bradshaw ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Extracellular Dna ◽  
Sequencing Analysis ◽  
Reduced Representation ◽  
Genome Wide ◽  
A Genome ◽  
The Matrix ◽  
Genes Encoding ◽  
Mutant Phenotypes

Staphylococcus aureusis a leading cause of both nosocomial and community-acquired infection. Biofilm formation at the site of infection reduces antimicrobial susceptibility and can lead to chronic infection. During biofilm formation, a subset of cells liberate cytoplasmic proteins and DNA, which are repurposed to form the extracellular matrix that binds the remaining cells together in large clusters. Using a strain that forms robust biofilms in vitro during growth under glucose supplementation, we carried out a genome-wide screen for genes involved in the release of extracellular DNA (eDNA). A high-density transposon insertion library was grown under biofilm-inducing conditions, and the relative frequency of insertions was compared between genomic DNA (gDNA) collected from cells in the biofilm and eDNA from the matrix. Transposon insertions into genes encoding functions necessary for eDNA release were identified by reduced representation in the eDNA. On direct testing, mutants of some of these genes exhibited markedly reduced levels of eDNA and a concomitant reduction in cell clustering. Among the genes with robust mutant phenotypes weregdpP, which encodes a phosphodiesterase that degrades the second messenger cyclic-di-AMP, andxdrA, the gene for a transcription factor that, as revealed by RNA-sequencing analysis, influences the expression of multiple genes, including many involved in cell wall homeostasis. Finally, we report that growth in biofilm-inducing medium lowers cyclic-di-AMP levels and does so in a manner that depends on thegdpPphosphodiesterase gene.

scholarly journals The Genetic Architecture of Ovariole Number in Drosophila melanogaster: Genes with Major, Quantitative, and Pleiotropic Effects

2017 ◽  
Vol 7 (7) ◽  
pp. 2391-2403 ◽  
Author(s):  
Amanda S Lobell ◽  
Rachel R Kaspari ◽  
Yazmin L Serrano Negron ◽  
Susan T Harbison
Keyword(s):  
Candidate Genes ◽  
Genome Wide Association Study ◽  
Natural Populations ◽  
Direct Role ◽  
Genome Wide ◽  
A Genome ◽  
Fitness Trait ◽  
Sleep Parameters ◽  
Activity Behavior ◽  
Ovariole Number

Abstract Ovariole number has a direct role in the number of eggs produced by an insect, suggesting that it is a key morphological fitness trait. Many studies have documented the variability of ovariole number and its relationship to other fitness and life-history traits in natural populations of Drosophila. However, the genes contributing to this variability are largely unknown. Here, we conducted a genome-wide association study of ovariole number in a natural population of flies. Using mutations and RNAi-mediated knockdown, we confirmed the effects of 24 candidate genes on ovariole number, including a novel gene, anneboleyn (formerly CG32000), that impacts both ovariole morphology and numbers of offspring produced. We also identified pleiotropic genes between ovariole number traits and sleep and activity behavior. While few polymorphisms overlapped between sleep parameters and ovariole number, 39 candidate genes were nevertheless in common. We verified the effects of seven genes on both ovariole number and sleep: bin3, blot, CG42389, kirre, slim, VAChT, and zfh1. Linkage disequilibrium among the polymorphisms in these common genes was low, suggesting that these polymorphisms may evolve independently.

scholarly journals Transcriptome analysis ofSchistosoma mansonilarval development using serial analysis of gene expression (SAGE)

Parasitology ◽  
2009 ◽  
Vol 136 (5) ◽  
pp. 469-485 ◽  
Author(s):  
A. S. TAFT ◽  
J. J. VERMEIRE ◽  
J. BERNIER ◽  
S. R. BIRKELAND ◽  
M. J. CIPRIANO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sequence Data ◽  
Subsequent Development ◽  
Differentially Expressed ◽  
Cdna Libraries ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Expression ◽  
Cell Conditioned Medium

SUMMARYInfection of the snail,Biomphalaria glabrata, by the free-swimming miracidial stage of the human blood fluke,Schistosoma mansoni, and its subsequent development to the parasitic sporocyst stage is critical to establishment of viable infections and continued human transmission. We performed a genome-wide expression analysis of theS. mansonimiracidia and developing sporocyst using Long Serial Analysis of Gene Expression (LongSAGE). Five cDNA libraries were constructed from miracidia andin vitrocultured 6- and 20-day-old sporocysts maintained in sporocyst medium (SM) or in SM conditioned by previous cultivation with cells of theB. glabrataembryonic (Bge) cell line. We generated 21 440 SAGE tags and mapped 13 381 to theS. mansonigene predictions (v4.0e) either by estimating theoretical 3′ UTR lengths or using existing 3′ EST sequence data. Overall, 432 transcripts were found to be differentially expressed amongst all 5 libraries. In total, 172 tags were differentially expressed between miracidia and 6-day conditioned sporocysts and 152 were differentially expressed between miracidia and 6-day unconditioned sporocysts. In addition, 53 and 45 tags, respectively, were differentially expressed in 6-day and 20-day cultured sporocysts, due to the effects of exposure to Bge cell-conditioned medium.

scholarly journals The FAM171A2 gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases

2020 ◽  
Vol 6 (43) ◽  
pp. eabb3063
Author(s):  
Wei Xu ◽  
Si-Da Han ◽  
Can Zhang ◽  
Jie-Qiong Li ◽  
Yan-Jiang Wang ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Genome Wide Association Study ◽  
In Vitro Study ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Pathophysiological Role ◽  
Independent Cohort

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10−12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

scholarly journals Complete biosynthetic pathways of ascofuranone and ascochlorin inAcremonium egyptiacum

2019 ◽  
Vol 116 (17) ◽  
pp. 8269-8274 ◽  
Author(s):  
Yasuko Araki ◽  
Takayoshi Awakawa ◽  
Motomichi Matsuzaki ◽  
Rihe Cho ◽  
Yudai Matsuda ◽  
...  
Keyword(s):  
Differential Expression Analysis ◽  
Cost Effective ◽  
Drug Candidate ◽  
P450 Monooxygenase ◽  
Genome Wide ◽  
Common Precursor ◽  
A Genome ◽  
Membrane Bound ◽  
The Cost

Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, includingAcremonium egyptiacum(synonym:Acremonium sclerotigenum), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanosomiasis and a potential anticancer lead compound. These compounds are supposedly biosynthesized through farnesylation of orsellinic acid, but the details have not been established. In this study, we present all of the reactions and responsible genes for AF and AC biosyntheses inA. egyptiacum, identified by heterologous expression, in vitro reconstruction, and gene deletion experiments with the aid of a genome-wide differential expression analysis. Both pathways share the common precursor, ilicicolin A epoxide, which is processed by the membrane-bound terpene cyclase (TPC) AscF in AC biosynthesis. AF biosynthesis branches from the precursor by hydroxylation at C-16 by the P450 monooxygenase AscH, followed by cyclization by a membrane-bound TPC AscI. All genes required for AC biosynthesis (ascABCDEFG) and a transcriptional factor (ascR) form a functional gene cluster, whereas those involved in the late steps of AF biosynthesis (ascHIJ) are present in another distantly located cluster. AF is therefore a rare example of fungal secondary metabolites requiring multilocus biosynthetic clusters, which are likely to be controlled by the single regulator, AscR. Finally, we achieved the selective production of AF inA. egyptiacumby genetically blocking the AC biosynthetic pathway; further manipulation of the strain will lead to the cost-effective mass production required for the clinical use of AF.

In vitro-targeted gene identification in patients with hepatitis C using a genome-wide microarray technology

Hepatology ◽  
2008 ◽  
Vol 49 (2) ◽  
pp. 378-386 ◽  
Author(s):  
Susanne Hagist ◽  
Holger Sültmann ◽  
Gunda Millonig ◽  
Ulrike Hebling ◽  
Dörthe Kieslich ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Gene Identification ◽  
Microarray Technology ◽  
Genome Wide ◽  
A Genome

scholarly journals Predicting the Landscape of Recombination Using Deep Learning

2020 ◽  
Vol 37 (6) ◽  
pp. 1790-1808 ◽  
Author(s):  
Jeffrey R Adrion ◽  
Jared G Galloway ◽  
Andrew D Kern
Keyword(s):  
Deep Learning ◽  
Evolutionary History ◽  
Model Misspecification ◽  
Natural Populations ◽  
High Accuracy ◽  
Demographic Model ◽  
Recombination Rates ◽  
Genome Wide ◽  
A Genome ◽  
The Face

Abstract Accurately inferring the genome-wide landscape of recombination rates in natural populations is a central aim in genomics, as patterns of linkage influence everything from genetic mapping to understanding evolutionary history. Here, we describe recombination landscape estimation using recurrent neural networks (ReLERNN), a deep learning method for estimating a genome-wide recombination map that is accurate even with small numbers of pooled or individually sequenced genomes. Rather than use summaries of linkage disequilibrium as its input, ReLERNN takes columns from a genotype alignment, which are then modeled as a sequence across the genome using a recurrent neural network. We demonstrate that ReLERNN improves accuracy and reduces bias relative to existing methods and maintains high accuracy in the face of demographic model misspecification, missing genotype calls, and genome inaccessibility. We apply ReLERNN to natural populations of African Drosophila melanogaster and show that genome-wide recombination landscapes, although largely correlated among populations, exhibit important population-specific differences. Lastly, we connect the inferred patterns of recombination with the frequencies of major inversions segregating in natural Drosophila populations.

scholarly journals A Genome-Wide Proteome Array Reveals a Limited Set of Immunogens in Natural Infections of Humans and White-Footed Mice with Borrelia burgdorferi

2008 ◽  
Vol 76 (8) ◽  
pp. 3374-3389 ◽  
Author(s):  
Alan G. Barbour ◽  
Algimantas Jasinskas ◽  
Matthew A. Kayala ◽  
D. Huw Davies ◽  
Allen C. Steere ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Lyme Borreliosis ◽  
Flagellar Apparatus ◽  
Reading Frame ◽  
High Ranking ◽  
Paralogous Family ◽  
Genome Wide ◽  
A Genome ◽  
Statistical Criteria

ABSTRACT Humans and other animals with Lyme borreliosis produce antibodies to a number of components of the agent Borrelia burgdorferi, but a full accounting of the immunogens during natural infections has not been achieved. Employing a protein array produced in vitro from 1,292 DNA fragments representing ∼80% of the genome, we compared the antibody reactivities of sera from patients with early or later Lyme borreliosis to the antibody reactivities of sera from controls. Overall, ∼15% of the open reading frame (ORF) products (Orfs) of B. burgdorferi in the array detectably elicited an antibody response in humans with natural infections. Among the immunogens, 103 stood out on the basis of statistical criteria. The majority of these Orfs were also immunogenic with sera obtained from naturally infected Peromyscus leucopus mice, a major reservoir. The high-ranking set included several B. burgdorferi proteins hitherto unrecognized as immunogens, as well as several proteins that have been established as antigens. The high-ranking immunogens were more likely than nonreactive Orfs to have the following characteristics: (i) plasmid-encoded rather than chromosome-encoded proteins, (ii) a predicted lipoprotein, and (iii) a member of a paralogous family of proteins, notably the Bdr and Erp proteins. The newly discovered antigens included Orfs encoded by several ORFs of the lp36 linear plasmid, such as BBK07 and BBK19, and proteins of the flagellar apparatus, such as FliL. These results indicate that the majority of deduced proteins of B. burgdorferi do not elicit antibody responses during infection and that the limited sets of immunogens are similar for two different host species.

Identifying biofilm regulators as novel targets for antimicrobial drug design

2020 ◽  
Author(s):  
Melanie Dostert ◽  
Corrie R Belanger ◽  
Travis M Blimkie ◽  
Reza Falsafi ◽  
Bhavjinder K Dhillon ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Immunocompromised Patients ◽  
Nosocomial Pathogen ◽  
Burn Wound ◽  
Antibiotic Resistant ◽  
Metabolic Genes ◽  
Genome Wide ◽  
A Genome ◽  
Novel Targets ◽  
Hypothetical Genes

<p>Antibiotic treatment regularly fails to cure patients suffering from infections caused by adaptively resistant microbial communities, referred to as biofilms. Even though at least two thirds of all clinical infections are associated with biofilms, there are no biofilm-specific therapies on the market or in clinical trials. <em>Pseudomonas aeruginosa</em> is a remarkably antibiotic resistant, nosocomial pathogen and biofilm-former that causes morbidity and mortality especially in cystic fibrosis and immunocompromised patients. This project aims to identify regulatory genes associated with drug resistance in <em>P. aeruginosa</em> biofilms to provide novel biofilm-specific targets for the design of potent drugs. A genome-wide screen of <em>P. aeruginosa</em> burn wound isolate UCBPP-PA14 identified 362 genes involved in biofilm formation, including dozens of regulatory and hypothetical genes. I will discuss regulatory as well as metabolic genes corresponding to the known resistome of antimicrobials.</p>

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