Genes

20 pages, 3706 KiB

Open AccessArticle

Comparative Genomics and Description of Putative Virulence Factors of Melissococcus plutonius, the Causative Agent of European Foulbrood Disease in Honey Bees

by Marvin Djukic, Silvio Erler, Andreas Leimbach, Daniela Grossar, Jean-Daniel Charrière, Laurent Gauthier, Denise Hartken, Sascha Dietrich, Heiko Nacke, Rolf Daniel and Anja Poehlein

Genes 2018, 9(8), 419; https://doi.org/10.3390/genes9080419 - 20 Aug 2018

Cited by 32 | Viewed by 6867

Abstract

In Europe, approximately 84% of cultivated crop species depend on insect pollinators, mainly bees. Apis mellifera (the Western honey bee) is the most important commercial pollinator worldwide. The Gram-positive bacterium Melissococcus plutonius is the causative agent of European foulbrood (EFB), a global honey [...] Read more.

In Europe, approximately 84% of cultivated crop species depend on insect pollinators, mainly bees. Apis mellifera (the Western honey bee) is the most important commercial pollinator worldwide. The Gram-positive bacterium Melissococcus plutonius is the causative agent of European foulbrood (EFB), a global honey bee brood disease. In order to detect putative virulence factors, we sequenced and analyzed the genomes of 14 M. plutonius strains, including two reference isolates. The isolates do not show a high diversity in genome size or number of predicted protein-encoding genes, ranging from 2.021 to 2.101 Mbp and 1589 to 1686, respectively. Comparative genomics detected genes that might play a role in EFB pathogenesis and ultimately in the death of the honey bee larvae. These include bacteriocins, bacteria cell surface- and host cell adhesion-associated proteins, an enterococcal polysaccharide antigen, an epsilon toxin, proteolytic enzymes, and capsule-associated proteins. In vivo expression of three putative virulence factors (endo-alpha-N-acetylgalactosaminidase, enhancin and epsilon toxin) was verified using naturally infected larvae. With our strain collection, we show for the first time that genomic differences exist between non-virulent and virulent typical strains, as well as a highly virulent atypical strain, that may contribute to the virulence of M. plutonius. Finally, we also detected a high number of conserved pseudogenes (75 to 156) per genome, which indicates genomic reduction during evolutionary host adaptation. Full article

(This article belongs to the Section Microbial Genetics and Genomics)

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12 pages, 2979 KiB

Open AccessArticle

Pathogen Species Identification from Metagenomes in Ancient Remains: The Challenge of Identifying Human Pathogenic Species of Trypanosomatidae via Bioinformatic Tools

by Denis Sereno, Franck Dorkeld, Mohammad Akhoundi and Pascale Perrin

Genes 2018, 9(8), 418; https://doi.org/10.3390/genes9080418 - 20 Aug 2018

Cited by 5 | Viewed by 5134

Abstract

Accurate species identification from ancient DNA samples is a difficult task that would shed light on the evolutionary history of pathogenic microorganisms. The field of palaeomicrobiology has undoubtedly benefited from the advent of untargeted metagenomic approaches that use next-generation sequencing methodologies. Nevertheless, assigning [...] Read more.

Accurate species identification from ancient DNA samples is a difficult task that would shed light on the evolutionary history of pathogenic microorganisms. The field of palaeomicrobiology has undoubtedly benefited from the advent of untargeted metagenomic approaches that use next-generation sequencing methodologies. Nevertheless, assigning ancient DNA at the species level is a challenging process. Recently, the gut microbiome analysis of three pre-Columbian Andean mummies (Santiago-Rodriguez et al., 2016) has called into question the identification of Leishmania in South America. The accurate assignment would be important because it will provide some key elements that are linked to the evolutionary scenario for visceral leishmaniasis agents in South America. Here, we recovered the metagenomic data filed in the metagenomics RAST server (MG-RAST) to identify the different members of the Trypanosomatidae family that have infected these ancient remains. For this purpose, we used the ultrafast metagenomic sequence classifier, based on an exact alignment of k-mers (Kraken) and Bowtie2, an ultrafast and memory-efficient tool for aligning sequencing reads to long reference sequences. The analyses, which have been conducted on the most exhaustive genomic database possible on Trypanosomatidae, show that species assignments could be biased by a lack of some genomic sequences of Trypanosomatidae species (strains). Nevertheless, our work raises the issue of possible co-infections by multiple members of the Trypanosomatidae family in these three pre-Columbian mummies. In the three mummies, we show the presence of DNA that is reminiscent of a probable co-infection with Leptomonas seymouri, a parasite of insect’s gut, and Lotmaria. Full article

(This article belongs to the Special Issue Microbial Paleogenomics: The Role of Microbes on Evolutionary Trends and Future Discoveries)

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6 pages, 1001 KiB

Open AccessConcept Paper

Membrane Surface Features of Blastocystis Subtypes

by John Anthony Yason and Kevin Shyong Wei Tan

Genes 2018, 9(8), 417; https://doi.org/10.3390/genes9080417 - 17 Aug 2018

Cited by 11 | Viewed by 4298

Abstract

Blastocystis is a common intestinal protistan parasite with global distribution. Blastocystis is a species complex composed of several isolates with biological and morphological differences. The surface coats of Blastocystis from three different isolates representing three subtypes were analyzed using scanning electron microscopy. This [...] Read more.

Blastocystis is a common intestinal protistan parasite with global distribution. Blastocystis is a species complex composed of several isolates with biological and morphological differences. The surface coats of Blastocystis from three different isolates representing three subtypes were analyzed using scanning electron microscopy. This structure contains carbohydrate components that are also present in surface glycoconjugates in other parasitic protozoa. Electron micrographs show variations in the surface coats from the three Blastocystis isolates. These differences could be associated with the differences in the pathogenic potential of Blastocystis subtypes. Apart from the surface coat, a plasma membrane-associated surface antigen has been described for Blastocystis ST7 and is associated with programmed cell death features of the parasite. Full article

(This article belongs to the Special Issue Membrane Proteins in Parasitic Protozoa)

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28 pages, 9171 KiB

Open AccessFeature PaperReview

Maneuvers on PCNA Rings during DNA Replication and Repair

by Dea Slade

Genes 2018, 9(8), 416; https://doi.org/10.3390/genes9080416 - 17 Aug 2018

Cited by 62 | Viewed by 14937

Abstract

DNA replication and repair are essential cellular processes that ensure genome duplication and safeguard the genome from deleterious mutations. Both processes utilize an abundance of enzymatic functions that need to be tightly regulated to ensure dynamic exchange of DNA replication and repair factors. [...] Read more.

DNA replication and repair are essential cellular processes that ensure genome duplication and safeguard the genome from deleterious mutations. Both processes utilize an abundance of enzymatic functions that need to be tightly regulated to ensure dynamic exchange of DNA replication and repair factors. Proliferating cell nuclear antigen (PCNA) is the major coordinator of faithful and processive replication and DNA repair at replication forks. Post-translational modifications of PCNA, ubiquitination and acetylation in particular, regulate the dynamics of PCNA-protein interactions. Proliferating cell nuclear antigen (PCNA) monoubiquitination elicits ‘polymerase switching’, whereby stalled replicative polymerase is replaced with a specialized polymerase, while PCNA acetylation may reduce the processivity of replicative polymerases to promote homologous recombination-dependent repair. While regulatory functions of PCNA ubiquitination and acetylation have been well established, the regulation of PCNA-binding proteins remains underexplored. Considering the vast number of PCNA-binding proteins, many of which have similar PCNA binding affinities, the question arises as to the regulation of the strength and sequence of their binding to PCNA. Here I provide an overview of post-translational modifications on both PCNA and PCNA-interacting proteins and discuss their relevance for the regulation of the dynamic processes of DNA replication and repair. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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14 pages, 698 KiB

Open AccessArticle

Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size

by Yury A. Barbitoff, Elena A. Serebryakova, Yulia A. Nasykhova, Alexander V. Predeus, Dmitrii E. Polev, Anna R. Shuvalova, Evgenii V. Vasiliev, Stanislav P. Urazov, Andrey M. Sarana, Sergey G. Scherbak, Dmitrii V. Gladyshev, Maria S. Pokrovskaya, Oksana V. Sivakova, Aleksey N. Meshkov, Oxana M. Drapkina, Oleg S. Glotov and Andrey S. Glotov

Genes 2018, 9(8), 415; https://doi.org/10.3390/genes9080415 - 17 Aug 2018

Cited by 23 | Viewed by 6389

Abstract

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate [...] Read more.

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10⁻⁵), rs112984085 in VAV3 (p = 4.8 × 10⁻⁴) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10⁻⁴), rs34042554 in PCDHA1 (p = 1 × 10⁻⁴), and rs144183813 in PLEKHA5 (p = 1.7 × 10⁻⁴) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10⁻⁵), and rs685523 in ADAMTS13 (p = 1 × 10⁻⁶) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations. Full article

(This article belongs to the Special Issue Computational Approaches for Disease Gene Identification)

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12 pages, 3243 KiB

Open AccessArticle

Genome-Wide Quantification of the Effect of Gene Overexpression on Escherichia coli Growth

by Hao Chen, Sumana Venkat, Jessica Wilson, Paige McGuire, Abigail L. Chang, Qinglei Gan and Chenguang Fan

Genes 2018, 9(8), 414; https://doi.org/10.3390/genes9080414 - 16 Aug 2018

Cited by 11 | Viewed by 4400

Abstract

Recombinant protein production plays an essential role in both biological studies and pharmaceutical production. Escherichia coli is one of the most favorable hosts for this purpose. Although a number of strategies for optimizing protein production have been developed, the effect of gene overexpression [...] Read more.

Recombinant protein production plays an essential role in both biological studies and pharmaceutical production. Escherichia coli is one of the most favorable hosts for this purpose. Although a number of strategies for optimizing protein production have been developed, the effect of gene overexpression on host cell growth has been much less studied. Here, we performed high-throughput tests on the E. coli a complete set of E. coli K-12 ORF archive (ASKA) collection to quantify the effects of overexpressing individual E. coli genes on its growth. The results indicated that overexpressing membrane-associated proteins or proteins with high abundances of branched-chain amino acids tended to impair cell growth, the latter of which could be remedied by amino acid supplementation. Through this study, we expect to provide an index for a fast pre-study estimate of host cell growth in order to choose proper rescuing approaches when working with different proteins. Full article

(This article belongs to the Special Issue Synthetic DNA and RNA Programming)

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29 pages, 3918 KiB

Open AccessArticle

Proteome-Wide Analysis of Trypanosoma cruzi Exponential and Stationary Growth Phases Reveals a Subcellular Compartment-Specific Regulation

by Carla Cristi Avila, Simon Ngao Mule, Livia Rosa-Fernandes, Rosa Viner, María Julia Barisón, André Guillherme Costa-Martins, Gilberto Santos De Oliveira, Marta Maria Geraldes Teixeira, Claudio Romero Farias Marinho, Ariel Mariano Silber and Giuseppe Palmisano

Genes 2018, 9(8), 413; https://doi.org/10.3390/genes9080413 - 15 Aug 2018

Cited by 24 | Viewed by 5675

Abstract

Trypanosoma cruzi, the etiologic agent of Chagas disease, cycles through different life stages characterized by defined molecular traits associated with the proliferative or differentiation state. In particular, T. cruzi epimastigotes are the replicative forms that colonize the intestine of the Triatomine insect [...] Read more.

Trypanosoma cruzi, the etiologic agent of Chagas disease, cycles through different life stages characterized by defined molecular traits associated with the proliferative or differentiation state. In particular, T. cruzi epimastigotes are the replicative forms that colonize the intestine of the Triatomine insect vector before entering the stationary phase that is crucial for differentiation into metacyclic trypomastigotes, which are the infective forms of mammalian hosts. The transition from proliferative exponential phase to quiescent stationary phase represents an important step that recapitulates the early molecular events of metacyclogenesis, opening new possibilities for understanding this process. In this study, we report a quantitative shotgun proteomic analysis of the T. cruzi epimastigote in the exponential and stationary growth phases. More than 3000 proteins were detected and quantified, highlighting the regulation of proteins involved in different subcellular compartments. Ribosomal proteins were upregulated in the exponential phase, supporting the higher replication rate of this growth phase. Autophagy-related proteins were upregulated in the stationary growth phase, indicating the onset of the metacyclogenesis process. Moreover, this study reports the regulation of N-terminally acetylated proteins during growth phase transitioning, adding a new layer of regulation to this process. Taken together, this study reports a proteome-wide rewiring during T. cruzi transit from the replicative exponential phase to the stationary growth phase, which is the preparatory phase for differentiation. Full article

(This article belongs to the Special Issue Membrane Proteins in Parasitic Protozoa)

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Graphical abstract

19 pages, 1304 KiB

Open AccessReview

Protein Import into the Endosymbiotic Organelles of Apicomplexan Parasites

by Natalia Mallo, Justin Fellows, Carla Johnson and Lilach Sheiner

Genes 2018, 9(8), 412; https://doi.org/10.3390/genes9080412 - 14 Aug 2018

Cited by 14 | Viewed by 7453

Abstract

The organelles of endosymbiotic origin, plastids, and mitochondria, evolved through the serial acquisition of endosymbionts by a host cell. These events were accompanied by gene transfer from the symbionts to the host, resulting in most of the organellar proteins being encoded in the [...] Read more.

The organelles of endosymbiotic origin, plastids, and mitochondria, evolved through the serial acquisition of endosymbionts by a host cell. These events were accompanied by gene transfer from the symbionts to the host, resulting in most of the organellar proteins being encoded in the cell nuclear genome and trafficked into the organelle via a series of translocation complexes. Much of what is known about organelle protein translocation mechanisms is based on studies performed in common model organisms; e.g., yeast and humans or Arabidopsis. However, studies performed in divergent organisms are gradually accumulating. These studies provide insights into universally conserved traits, while discovering traits that are specific to organisms or clades. Apicomplexan parasites feature two organelles of endosymbiotic origin: a secondary plastid named the apicoplast and a mitochondrion. In the context of the diseases caused by apicomplexan parasites, the essential roles and divergent features of both organelles make them prime targets for drug discovery. This potential and the amenability of the apicomplexan Toxoplasma gondii to genetic manipulation motivated research about the mechanisms controlling both organelles’ biogenesis. Here we provide an overview of what is known about apicomplexan organelle protein import. We focus on work done mainly in T. gondii and provide a comparison to model organisms. Full article

(This article belongs to the Special Issue Membrane Proteins in Parasitic Protozoa)

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13 pages, 1493 KiB

Open AccessArticle

Pervasive Modulation of Obesity Risk by the Environment and Genomic Background

by Sini Nagpal, Greg Gibson and Urko M. Marigorta

Genes 2018, 9(8), 411; https://doi.org/10.3390/genes9080411 - 14 Aug 2018

Cited by 16 | Viewed by 5825

Abstract

The prevalence of the so-called diseases of affluence, such as type 2 diabetes or hypertension, has increased dramatically in the last two generations. Although genome-wide association studies (GWAS) have discovered hundreds of genes involved in disease etiology, the sudden increase in disease incidence [...] Read more.

The prevalence of the so-called diseases of affluence, such as type 2 diabetes or hypertension, has increased dramatically in the last two generations. Although genome-wide association studies (GWAS) have discovered hundreds of genes involved in disease etiology, the sudden increase in disease incidence suggests a major role for environmental risk factors. Obesity constitutes a case example of a modern trait shaped by contemporary environment, although with considerable debates about the extent to which gene-by-environment (G×E) interactions accentuate obesity risk in individuals following obesogenic lifestyles. Although interaction effects have been robustly confirmed at the FTO locus, accumulating evidence at the genome-wide level implicates a role for polygenic risk-by-environment interactions. Through a variety of analyses using the UK Biobank, we confirm that the genomic background plays a major role in shaping the expressivity of alleles that increase body mass index (BMI). Full article

(This article belongs to the Special Issue Evolutionary Medicine)

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9 pages, 358 KiB

Open AccessBrief Report

Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

by Daniel Castellano-Castillo, Isabel Moreno-Indias, Jose Carlos Fernandez-Garcia, Mercedes Clemente-Postigo, Manuel Castro-Cabezas, Francisco José Tinahones, María Isabel Queipo-Ortuño and Fernando Cardona

Genes 2018, 9(8), 410; https://doi.org/10.3390/genes9080410 - 13 Aug 2018

Cited by 14 | Viewed by 4683

Abstract

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns [...] Read more.

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism. Full article

(This article belongs to the Special Issue Advances in Genetics of Regeneration in Metabesity)

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12 pages, 2028 KiB

Open AccessReview

Using the Mutation-Selection Framework to Characterize Selection on Protein Sequences

by Ashley I. Teufel, Andrew M. Ritchie, Claus O. Wilke and David A. Liberles

Genes 2018, 9(8), 409; https://doi.org/10.3390/genes9080409 - 13 Aug 2018

Cited by 10 | Viewed by 4164

Abstract

When mutational pressure is weak, the generative process of protein evolution involves explicit probabilities of mutations of different types coupled to their conditional probabilities of fixation dependent on selection. Establishing this mechanistic modeling framework for the detection of selection has been a goal [...] Read more.

When mutational pressure is weak, the generative process of protein evolution involves explicit probabilities of mutations of different types coupled to their conditional probabilities of fixation dependent on selection. Establishing this mechanistic modeling framework for the detection of selection has been a goal in the field of molecular evolution. Building on a mathematical framework proposed more than a decade ago, numerous methods have been introduced in an attempt to detect and measure selection on protein sequences. In this review, we discuss the structure of the original model, subsequent advances, and the series of assumptions that these models operate under. Full article

(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)

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12 pages, 1072 KiB

Open AccessArticle

Authenticity Testing and Detection of Eurycoma longifolia in Commercial Herbal Products Using Bar-High Resolution Melting Analysis

by Nur Fadhila Fadzil, Alina Wagiran, Faezah Mohd Salleh, Shamsiah Abdullah and Nur Hazwani Mohd Izham

Genes 2018, 9(8), 408; https://doi.org/10.3390/genes9080408 - 12 Aug 2018

Cited by 19 | Viewed by 4326

Abstract

The present study demonstrated High Resolution Melting (HRM) analysis combined with DNA barcode (Bar-HRM) as a fast and highly sensitive technique for detecting adulterants in Eurycoma longifolia commercial herbal products. Targeting the DNA barcoding of the chloroplastic region-ribulose biphosphate carboxylase large chain (rbcL) [...] Read more.

The present study demonstrated High Resolution Melting (HRM) analysis combined with DNA barcode (Bar-HRM) as a fast and highly sensitive technique for detecting adulterants in Eurycoma longifolia commercial herbal products. Targeting the DNA barcoding of the chloroplastic region-ribulose biphosphate carboxylase large chain (rbcL) and the nuclear ribosomal region- internal transcribed spacer 2 (ITS2), PCR amplification and HRM analysis using saturated Eva green dye as the source of fluorescence signals, was accomplished by employing a real-time cycler. The results were further validated by sequencing to identify unknown sequence from Genbank database and to generate phylogenetic tree using neighbour joint (NJ) analysis. Both of the DNA markers exhibited a distinguishable melting temperature and shape of the normalised curve between the reference and the adulterants. In the case of species identification, ITS2 was more successful in differentiating between species. Additionally, detection of admixture sample containing small traces of targeted E. longifolia DNA (w/v) can be detected as low as 5% for rbcL and less than 1% for ITS2, proving the sensitivity and versatility of the HRM analysis. In conclusion, the Bar-HRM analysis is a fast and reliable technique that can effectively detect adulterants in herbal products. Therefore, this will be beneficial for regulatory agencies in order to regulate food safety issues. Full article

(This article belongs to the Special Issue DNA Barcoding and Metabarcoding of Complex Matrices)

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18 pages, 2378 KiB

Open AccessArticle

Seasonal and Sexual Differences in the Microbiota of the Hoopoe Uropygial Secretion

by Sonia M. Rodríguez-Ruano, Manuel Martín-Vivaldi, Juan M. Peralta-Sánchez, Ana B. García-Martín, Ángela Martínez-García, Juan J. Soler, Eva Valdivia and Manuel Martínez-Bueno

Genes 2018, 9(8), 407; https://doi.org/10.3390/genes9080407 - 11 Aug 2018

Cited by 14 | Viewed by 4228

Abstract

The uropygial gland of hoopoe nestlings and nesting females hosts bacterial symbionts that cause changes in the characteristics of its secretion, including an increase of its antimicrobial activity. These changes occur only in nesting individuals during the breeding season, possibly associated with the [...] Read more.

The uropygial gland of hoopoe nestlings and nesting females hosts bacterial symbionts that cause changes in the characteristics of its secretion, including an increase of its antimicrobial activity. These changes occur only in nesting individuals during the breeding season, possibly associated with the high infection risk experienced during the stay in the hole-nests. However, the knowledge on hoopoes uropygial gland microbial community dynamics is quite limited and based so far on culture-dependent and molecular fingerprinting studies. In this work, we sampled wild and captive hoopoes of different sex, age, and reproductive status, and studied their microbiota using quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH) and pyrosequencing. Surprisingly, we found a complex bacterial community in all individuals (including non-nesting ones) during the breeding season. Nevertheless, dark secretions from nesting hoopoes harbored significantly higher bacterial density than white secretions from breeding males and both sexes in winter. We hypothesize that bacterial proliferation may be host-regulated in phases of high infection risk (i.e., nesting). We also highlight the importance of specific antimicrobial-producing bacteria present only in dark secretions that may be key in this defensive symbiosis. Finally, we discuss the possible role of environmental conditions in shaping the uropygial microbiota, based on differences found between wild and captive hoopoes. Full article

(This article belongs to the Special Issue Coevolution of Hosts and their Microbiome)

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18 pages, 3131 KiB

Open AccessArticle

Nitrogen Supply and Leaf Age Affect the Expression of TaGS1 or TaGS2 Driven by a Constitutive Promoter in Transgenic Tobacco

by Yihao Wei, Aibo Shi, Xiting Jia, Zhiyong Zhang, Xinming Ma, Mingxin Gu, Xiaodan Meng and Xiaochun Wang

Genes 2018, 9(8), 406; https://doi.org/10.3390/genes9080406 - 10 Aug 2018

Cited by 23 | Viewed by 4378

Abstract

Glutamine synthetase (GS) plays a key role in nitrogen metabolism. Here, two types of tobacco transformants, overexpressing Triticum aestivum GS1 (TaGS1) or GS2 (TaGS2), were analysed. Four independent transformed lines, GS1-TR1, GS1-TR2, GS2-TR1 and GS2-TR2, were used for the nitrogen treatment. Under nitrogen-sufficient [...] Read more.

Glutamine synthetase (GS) plays a key role in nitrogen metabolism. Here, two types of tobacco transformants, overexpressing Triticum aestivum GS1 (TaGS1) or GS2 (TaGS2), were analysed. Four independent transformed lines, GS1-TR1, GS1-TR2, GS2-TR1 and GS2-TR2, were used for the nitrogen treatment. Under nitrogen-sufficient conditions, the leaves of GS2-TR showed high accumulation of the TaGS2 transcript, while those of GS1-TR showed a low TaGS1 transcript levels. However, compared with nitrogen-sufficient conditions, the TaGS1 transcript level increased in the leaves under nitrogen starvation, but the TaGS2 transcript level decreased. In addition, the TaGS1 and TaGS2 transcript levels were highest in the middle leaves under nitrogen-sufficient and starvation conditions. These results show that nitrogen supply and leaf age regulate TaGS expression, even when they are driven by a super-promoter. Additionally, in regard to nitrogen metabolism level, the lower leaves of the GS1-TR exhibited lower NH₄⁺ and higher amino acid contents, while the upper leaves exhibited higher amino acid, soluble protein and chlorophyll contents. The leaves of the GS2-TR exhibited lower NH₄⁺ but higher amino acid, soluble protein and chlorophyll contents. Given the role that GS isoforms play in nitrogen metabolism, these data suggest that TaGS1 overexpression may improve nitrogen transport, and that TaGS2 overexpression may improve nitrogen assimilation under nitrogen stress. Full article

(This article belongs to the Special Issue Improving Plant Nutrient Use efficiency)

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14 pages, 812 KiB

Open AccessArticle

Sequencing of Supernumerary Chromosomes of Red Fox and Raccoon Dog Confirms a Non-Random Gene Acquisition by B Chromosomes

by Alexey I. Makunin, Svetlana A. Romanenko, Violetta R. Beklemisheva, Polina L. Perelman, Anna S. Druzhkova, Kristina O. Petrova, Dmitry Yu. Prokopov, Ekaterina N. Chernyaeva, Jennifer L. Johnson, Anna V. Kukekova, Fengtang Yang, Malcolm A. Ferguson-Smith, Alexander S. Graphodatsky and Vladimir A. Trifonov

Genes 2018, 9(8), 405; https://doi.org/10.3390/genes9080405 - 10 Aug 2018

Cited by 22 | Viewed by 5782

Abstract

B chromosomes (Bs) represent a variable addition to the main karyotype in some lineages of animals and plants. Bs accumulate through non-Mendelian inheritance and become widespread in populations. Despite the presence of multiple genes, most Bs lack specific phenotypic effects, although their influence [...] Read more.

B chromosomes (Bs) represent a variable addition to the main karyotype in some lineages of animals and plants. Bs accumulate through non-Mendelian inheritance and become widespread in populations. Despite the presence of multiple genes, most Bs lack specific phenotypic effects, although their influence on host genome epigenetic status and gene expression are recorded. Previously, using sequencing of isolated Bs of ruminants and rodents, we demonstrated that Bs originate as segmental duplications of specific genomic regions, and subsequently experience pseudogenization and repeat accumulation. Here, we used a similar approach to characterize Bs of the red fox (Vulpes vulpes L.) and the Chinese raccoon dog (Nyctereutes procyonoides procyonoides Gray). We confirm the previous findings of the KIT gene on Bs of both species, but demostrate an independent origin of Bs in these species, with two reused regions. Comparison of gene ensembles in Bs of canids, ruminants, and rodents once again indicates enrichment with cell-cycle genes, development-related genes, and genes functioning in the neuron synapse. The presence of B-chromosomal copies of genes involved in cell-cycle regulation and tissue differentiation may indicate importance of these genes for B chromosome establishment. Full article

(This article belongs to the Special Issue Evolution, Composition and Regulation of Supernumerary B Chromosomes)

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13 pages, 658 KiB

Open AccessReview

Membrane-Associated Proteins in Giardia lamblia

by María C. Touz, Constanza Feliziani and Andrea S. Rópolo

Genes 2018, 9(8), 404; https://doi.org/10.3390/genes9080404 - 10 Aug 2018

Cited by 9 | Viewed by 5924

Abstract

The manner in which membrane-associated proteins interact with the membrane defines their subcellular fate and function. This interaction relies on the characteristics of the proteins, their journey after synthesis, and their interaction with other proteins or enzymes. Understanding these properties may help to [...] Read more.

The manner in which membrane-associated proteins interact with the membrane defines their subcellular fate and function. This interaction relies on the characteristics of the proteins, their journey after synthesis, and their interaction with other proteins or enzymes. Understanding these properties may help to define the function of a protein and also the role of an organelle. In the case of microorganisms like protozoa parasites, it may help to understand singular features that will eventually lead to the design of parasite-specific drugs. The protozoa parasite Giardia lamblia is an example of a widespread parasite that has been infecting humans and animals from ancestral times, adjusting itself to the changes of the environment inside and outside the host. Several membrane-associated proteins have been posted in the genome database GiardiaDB, although only a few of them have been characterized. This review discusses the data regarding membrane-associated proteins in relationship with lipids and specific organelles and their implication in the discovery of anti-giardial therapies. Full article

(This article belongs to the Special Issue Membrane Proteins in Parasitic Protozoa)

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21 pages, 3470 KiB

Open AccessArticle

Habitat Fragmentation Reduces Genetic Diversity and Connectivity of the Mexican Spotted Owl: A Simulation Study Using Empirical Resistance Models

by Ho Yi Wan, Samuel A. Cushman and Joseph L. Ganey

Genes 2018, 9(8), 403; https://doi.org/10.3390/genes9080403 - 10 Aug 2018

Cited by 31 | Viewed by 6793

Abstract

We evaluated how differences between two empirical resistance models for the same geographic area affected predictions of gene flow processes and genetic diversity for the Mexican spotted owl (Strix occidentalis lucida). The two resistance models represented the landscape under low- and [...] Read more.

We evaluated how differences between two empirical resistance models for the same geographic area affected predictions of gene flow processes and genetic diversity for the Mexican spotted owl (Strix occidentalis lucida). The two resistance models represented the landscape under low- and high-fragmentation parameters. Under low fragmentation, the landscape had larger but highly concentrated habitat patches, whereas under high fragmentation, the landscape had smaller habitat patches that scattered across a broader area. Overall habitat amount differed little between resistance models. We tested eight scenarios reflecting a factorial design of three factors: resistance model (low vs. high fragmentation), isolation hypothesis (isolation-by-distance, IBD, vs. isolation-by-resistance, IBR), and dispersal limit of species (200 km vs. 300 km). Higher dispersal limit generally had a positive but small influence on genetic diversity. Genetic distance increased with both geographic distance and landscape resistance, but landscape resistance displayed a stronger influence. Connectivity was positively related to genetic diversity under IBR but was less important under IBD. Fragmentation had a strong negative influence on the spatial patterns of genetic diversity and effective population size (Ns). Despite habitats being more concentrated and less widely distributed, the low-fragmentation landscape had greater genetic diversity than the high-fragmentation landscape, suggesting that highly concentrated but larger habitat patches may provide a genetic refuge for the Mexican spotted owl. Full article

(This article belongs to the Special Issue Landscape Genetics)

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42 pages, 2820 KiB

Open AccessArticle

Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers

by Ankit Hirpara, Mathew Bloomfield and Peter Duesberg

Genes 2018, 9(8), 402; https://doi.org/10.3390/genes9080402 - 9 Aug 2018

Cited by 9 | Viewed by 6013

Abstract

It has been known for over 100 years that cancers have individual karyotypes and arise only years to decades after initiating carcinogens. However, there is still no coherent theory to explain these definitive characteristics of cancer. The prevailing mutation theory holds that cancers [...] Read more.

It has been known for over 100 years that cancers have individual karyotypes and arise only years to decades after initiating carcinogens. However, there is still no coherent theory to explain these definitive characteristics of cancer. The prevailing mutation theory holds that cancers are late because the primary cell must accumulate 3–8 causative mutations to become carcinogenic and that mutations, which induce chromosomal instability (CIN), generate the individual karyotypes of cancers. However, since there is still no proven set of mutations that transforms a normal to a cancer cell, we have recently advanced the theory that carcinogenesis is a form of speciation. This theory predicts carcinogens initiate cancer by inducing aneuploidy, which automatically unbalances thousands of genes and thus catalyzes chain-reactions of progressive aneuploidizations. Over time, these aneuploidizations have two endpoints, either non-viable karyotypes or very rarely karyotypes of new autonomous and immortal cancers. Cancer karyotypes are immortalized despite destabilizing congenital aneuploidy by clonal selections for autonomy—similar to those of conventional species. This theory predicts that the very low probability of converting the karyotype of a normal cell to that of a new autonomous cancer species by random aneuploidizations is the reason for the karyotypic individuality of new cancers and for the long latencies from carcinogens to cancers. In testing this theory, we observed: (1) Addition of mutagenic and non-mutagenic carcinogens to normal human and rat cells generated progressive aneuploidizations months before neoplastic transformation. (2) Sub-cloning of a neoplastic rat clone revealed heritable individual karyotypes, rather than the non-heritable karyotypes predicted by the CIN theory. (3) Analyses of neoplastic and preneoplastic karyotypes unexpectedly identified karyotypes with sets of 3–12 new marker chromosomes without detectable intermediates, consistent with single-step origins. We conclude that the speciation theory explains logically the long latencies from carcinogen exposure and the individuality of cancers. In addition, the theory supports the single-step origins of cancers, because karyotypic autonomy is all-or-nothing. Accordingly, we propose that preneoplastic aneuploidy and clonal neoplastic karyotypes provide more reliable therapeutic indications than current analyses of thousands of mutations. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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11 pages, 9550 KiB

Open AccessFeature PaperArticle

Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans

by Ana Carolina Remondi Souza, Beth Burgwyn Fuchs, Viviane De Souza Alves, Elamparithi Jayamani, Arnaldo Lopes Colombo and Eleftherios Mylonakis

Genes 2018, 9(8), 401; https://doi.org/10.3390/genes9080401 - 8 Aug 2018

Cited by 16 | Viewed by 5143

Abstract

Caenorhabditis elegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candida parapsilosis infection model by using the fungi as a food source. Three species of [...] Read more.

Caenorhabditis elegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candida parapsilosis infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (C. parapsilosis (sensu stricto), Candida orthopsilosis and Candida metapsilosis) caused infection resulting in C. elegans killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in C. elegans-Candida infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall, the C. elegans-C. parapsilosis infection model can be used to model C. parapsilosis host-pathogen interactions. Full article

(This article belongs to the Special Issue Fungal Pathogenesis in Humans: The Growing Threat)

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17 pages, 11961 KiB

Open AccessArticle

Golgi Reassembly and Stacking Protein (GRASP) Participates in Vesicle-Mediated RNA Export in Cryptococcus neoformans

by Roberta Peres da Silva, Sharon De Toledo Martins, Juliana Rizzo, Flavia C. G. Dos Reis, Luna S. Joffe, Marilene Vainstein, Livia Kmetzsch, Débora L. Oliveira, Rosana Puccia, Samuel Goldenberg, Marcio L. Rodrigues and Lysangela R. Alves

Genes 2018, 9(8), 400; https://doi.org/10.3390/genes9080400 - 8 Aug 2018

Cited by 28 | Viewed by 4736

Abstract

Golgi reassembly and stacking protein (GRASP) is required for polysaccharide secretion and virulence in Cryptococcus neoformans. In fungal species, extracellular vesicles (EVs) participate in the export of polysaccharides, proteins and RNA. In the present work, we investigated if EV-mediated RNA export is [...] Read more.

Golgi reassembly and stacking protein (GRASP) is required for polysaccharide secretion and virulence in Cryptococcus neoformans. In fungal species, extracellular vesicles (EVs) participate in the export of polysaccharides, proteins and RNA. In the present work, we investigated if EV-mediated RNA export is functionally connected with GRASP in C. neoformans using a graspΔ mutant. Since GRASP-mediated unconventional secretion involves autophagosome formation in yeast, we included the atg7Δ mutant with defective autophagic mechanisms in our analysis. All fungal strains exported EVs but deletion of GRASP or ATG7 profoundly affected vesicular dimensions. The mRNA content of the graspΔ EVs differed substantially from that of the other two strains. The transcripts associated to the endoplasmic reticulum were highly abundant transcripts in graspΔ EVs. Among non-coding RNAs (ncRNAs), tRNA fragments were the most abundant in both mutant EVs but graspΔ EVs alone concentrated 22 exclusive sequences. In general, our results showed that the EV RNA content from atg7Δ and WT were more related than the RNA content of graspΔ, suggesting that GRASP, but not the autophagy regulator Atg7, is involved in the EV export of RNA. This is a previously unknown function for a key regulator of unconventional secretion in eukaryotic cells. Full article

(This article belongs to the Special Issue Fungal Pathogenesis in Humans: The Growing Threat)

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18 pages, 6035 KiB

Open AccessArticle

OFP1 Interaction with ATH1 Regulates Stem Growth, Flowering Time and Flower Basal Boundary Formation in Arabidopsis

by Liguo Zhang, Lili Sun, Xiaofei Zhang, Shuquan Zhang, Dongwei Xie, Chunbo Liang, Wengong Huang, Lijuan Fan, Yuyan Fang and Ying Chang

Genes 2018, 9(8), 399; https://doi.org/10.3390/genes9080399 - 6 Aug 2018

Cited by 21 | Viewed by 5160

Abstract

Ovate Family Protein1 (OFP1) is a regulator, and it is suspected to be involved in plant growth and development. Meanwhile, Arabidopsis Thaliana Homeobox (ATH1), a BEL1-like homeodomain (HD) transcription factor, is known to be involved in regulating stem growth, flowering time and flower [...] Read more.

Ovate Family Protein1 (OFP1) is a regulator, and it is suspected to be involved in plant growth and development. Meanwhile, Arabidopsis Thaliana Homeobox (ATH1), a BEL1-like homeodomain (HD) transcription factor, is known to be involved in regulating stem growth, flowering time and flower basal boundary development in Arabidopsis. Previous large-scale yeast two-hybrid studies suggest that ATH1 possibly interact with OFP1, but this interaction is yet unverified. In our study, the interaction of OFP1 with ATH1 was verified using a directional yeast two-hybrid system and bimolecular fluorescence complementation (BiFC). Our results also demonstrated that the OFP1-ATH1 interaction is mainly controlled by the HD domain of ATH1. Meanwhile, we found that ATH1 plays the role of transcriptional repressor to regulate plant development and that OFP1 can enhance ATH1 repression function. Regardless of the mechanism, a putative functional role of ATH1-OFP1 may be to regulate the expression of the both the GA20ox1 gene, which is involved in gibberellin (GA) biosynthesis and control of stem elongation, and the Flowering Locus C (FLC) gene, which inhibits transition to flowering. Ultimately, the regulatory functional mechanism of OFP1-ATH1 may be complicated and diverse according to our results, and this work lays groundwork for further understanding of a unique and important protein–protein interaction that influences flowering time, stem development, and flower basal boundary development in plants. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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18 pages, 2730 KiB

Open AccessArticle

Genome-Wide Characterization of DNA Demethylase Genes and Their Association with Salt Response in Pyrus

by Chunxiao Liu, Hui Li, Jing Lin, Ying Wang, Xiaoyang Xu, Zong-Ming (Max) Cheng and Yonghong Chang

Genes 2018, 9(8), 398; https://doi.org/10.3390/genes9080398 - 6 Aug 2018

Cited by 19 | Viewed by 4240

Abstract

DNA methylation plays important roles in genome protection and the regulation of gene expression and it is associated with plants’ responses to environments. DNA demethylases are very important proteins in DNA methylation regulation. In this study, we performed genome-wide and deep analysis of [...] Read more.

DNA methylation plays important roles in genome protection and the regulation of gene expression and it is associated with plants’ responses to environments. DNA demethylases are very important proteins in DNA methylation regulation. In this study, we performed genome-wide and deep analysis of putative demethylases (DMEs) in pear. Seven DME genes were found in the pear genome and were defined as PbDME1–7 based on their domain organization. Results were supported by the gene structural characteristics and phylogenetic analysis. The gene structure of the DME genes were relatively complex and the DME7 proteins didn’t contain the Perm_CXXC domain. The DME genes experienced a whole genome duplication event (WGD) that occurred in the ancestor genome of pear and apple before their divergence based on the Ks values. Expression results showed that high salinity stress could influence the expression level of DMEs and salt-responsive genes in Pyrus betulaefolia. Furthermore, the methylation levels of salt-responsive genes changed under salt stress treatment. Results suggested important roles of PbDME genes in response to salt stress and are useful for better understanding the complex functions of this DME genes, which will facilitate epigenetic studies in pear trees salt tolerance. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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13 pages, 1738 KiB

Open AccessArticle

An Integrated Approach for Identifying Molecular Subtypes in Human Colon Cancer Using Gene Expression Data

by Wen-Hui Wang, Ting-Yan Xie, Guang-Lei Xie, Zhong-Lu Ren and Jin-Ming Li

Genes 2018, 9(8), 397; https://doi.org/10.3390/genes9080397 - 2 Aug 2018

Cited by 5 | Viewed by 4591

Abstract

Identifying molecular subtypes of colorectal cancer (CRC) may allow for more rational, patient-specific treatment. Various studies have identified molecular subtypes for CRC using gene expression data, but they are inconsistent and further research is necessary. From a methodological point of view, a progressive [...] Read more.

Identifying molecular subtypes of colorectal cancer (CRC) may allow for more rational, patient-specific treatment. Various studies have identified molecular subtypes for CRC using gene expression data, but they are inconsistent and further research is necessary. From a methodological point of view, a progressive approach is needed to identify molecular subtypes in human colon cancer using gene expression data. We propose an approach to identify the molecular subtypes of colon cancer that integrates denoising by the Bayesian robust principal component analysis (BRPCA) algorithm, hierarchical clustering by the directed bubble hierarchical tree (DBHT) algorithm, and feature gene selection by an improved differential evolution based feature selection method (DEFS_W) algorithm. In this approach, the normal samples being completely and exclusively clustered into one class is considered to be the standard of reasonable clustering subtypes, and the feature selection pays attention to imbalances of samples among subtypes. With this approach, we identified the molecular subtypes of colon cancer on the mRNA gene expression dataset of 153 colon cancer samples and 19 normal control samples of the Cancer Genome Atlas (TCGA) project. The colon cancer was clustered into 7 subtypes with 44 feature genes. Our approach could identify finer subtypes of colon cancer with fewer feature genes than the other two recent studies and exhibits a generic methodology that might be applied to identify the subtypes of other cancers. Full article

(This article belongs to the Special Issue Selected Papers from the Bioinformatics and Intelligent Information Processing Conference (BIIP2018))

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12 pages, 838 KiB

Open AccessArticle

Genomic Diversity of Listeria monocytogenes Isolated from Clinical and Non-Clinical Samples in Chile

by Viviana Toledo, Henk C. Den Bakker, Juan Carlos Hormazábal, Gerardo González-Rocha, Helia Bello-Toledo, Magaly Toro and Andrea I. Moreno-Switt

Genes 2018, 9(8), 396; https://doi.org/10.3390/genes9080396 - 2 Aug 2018

Cited by 28 | Viewed by 4987

Abstract

Listeria monocytogenes is the causative agent of listeriosis, which is an uncommon but severe infection associated with high mortality rates in humans especially in high-risk groups. This bacterium survives a variety of stress conditions (e.g., high osmolality, low pH), which allows it to [...] Read more.

Listeria monocytogenes is the causative agent of listeriosis, which is an uncommon but severe infection associated with high mortality rates in humans especially in high-risk groups. This bacterium survives a variety of stress conditions (e.g., high osmolality, low pH), which allows it to colonize different niches especially niches found in food processing environments. Additionally, a considerable heterogeneity in pathogenic potential has been observed in different strains. In this study, 38 isolates of L. monocytogenes collected in Chile from clinical samples (n = 22) and non-clinical samples (n = 16) were analyzed using whole genome sequencing (WGS) to determine their genomic diversity. A core genome Single Nucleotide Polymorphism (SNP) tree using 55 additional L. monocytogenes accessions classified the Chilean isolates in lineages I (n = 25) and II (n = 13). In silico, Multi-locus sequence typing (MLST) differentiated the isolates into 13 sequence types (ST) in which the most common were ST1 (15 isolates) and ST9 (6 isolates) and represented 55% of the isolates. Genomic elements associated with virulence (i.e., LIPI-1, LIPI-3, inlA, inlB, inlC, inlG, inlH, inlD, inlE, inlK, inlF, and inlJ) and stress survival (i.e., stress survival islet 1 and stress survival islet 2) were unevenly distributed among clinical and non-clinical isolates. In addition, one novel inlA premature stop codon (PMSC) was detected. Comparative analysis of L. monocytogenes circulating in Chile revealed the presence of globally distributed sequence types along with differences among the isolates analyzed at a genomic level specifically associated with virulence and stress survival. Full article

(This article belongs to the Special Issue Genetics and Genomics of Foodborne Pathogens)

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31 pages, 311 KiB

Open AccessArticle

Mitochondrial DNA Haplogroups and Breast Cancer Risk Factors in the Avon Longitudinal Study of Parents and Children (ALSPAC)

by Vivienne Riley, A Mesut Erzurumluoglu, Santiago Rodriguez and Carolina Bonilla

Genes 2018, 9(8), 395; https://doi.org/10.3390/genes9080395 - 1 Aug 2018

Cited by 8 | Viewed by 5094

Abstract

The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification [...] Read more.

The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry. Full article

(This article belongs to the Special Issue Evolutionary Medicine)

18 pages, 2858 KiB

Open AccessArticle

A Model Stacking Framework for Identifying DNA Binding Proteins by Orchestrating Multi-View Features and Classifiers

by Xiu-Juan Liu, Xiu-Jun Gong, Hua Yu and Jia-Hui Xu

Genes 2018, 9(8), 394; https://doi.org/10.3390/genes9080394 - 1 Aug 2018

Cited by 26 | Viewed by 4087

Abstract

Nowadays, various machine learning-based approaches using sequence information alone have been proposed for identifying DNA-binding proteins, which are crucial to many cellular processes, such as DNA replication, DNA repair and DNA modification. Among these methods, building a meaningful feature representation of the sequences [...] Read more.

Nowadays, various machine learning-based approaches using sequence information alone have been proposed for identifying DNA-binding proteins, which are crucial to many cellular processes, such as DNA replication, DNA repair and DNA modification. Among these methods, building a meaningful feature representation of the sequences and choosing an appropriate classifier are the most trivial tasks. Disclosing the significances and contributions of different feature spaces and classifiers to the final prediction is of the utmost importance, not only for the prediction performances, but also the practical clues of biological experiment designs. In this study, we propose a model stacking framework by orchestrating multi-view features and classifiers (MSFBinder) to investigate how to integrate and evaluate loosely-coupled models for predicting DNA-binding proteins. The framework integrates multi-view features including Local_DPP, 188D, Position-Specific Scoring Matrix (PSSM)_DWT and autocross-covariance of secondary structures(AC_Struc), which were extracted based on evolutionary information, sequence composition, physiochemical properties and predicted structural information, respectively. These features are fed into various loosely-coupled classifiers such as SVM and random forest. Then, a logistic regression model was applied to evaluate the contributions of these individual classifiers and to make the final prediction. When performing on the training dataset PDB1075, the proposed method achieves an accuracy of 83.53%. On the independent dataset PDB186, the method achieves an accuracy of 81.72%, which outperforms many existing methods. These results suggest that the framework is able to orchestrate various predicted models flexibly with good performances. Full article

(This article belongs to the Special Issue Selected Papers from the Bioinformatics and Intelligent Information Processing Conference (BIIP2018))

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18 pages, 1267 KiB

Open AccessFeature PaperArticle

A High-Quality, Long-Read De Novo Genome Assembly to Aid Conservation of Hawaiiʻs Last Remaining Crow Species

by Jolene T. Sutton, Martin Helmkampf, Cynthia C. Steiner, M. Renee Bellinger, Jonas Korlach, Richard Hall, Primo Baybayan, Jill Muehling, Jenny Gu, Sarah Kingan, Bryce M. Masuda and Oliver A. Ryder

Genes 2018, 9(8), 393; https://doi.org/10.3390/genes9080393 - 1 Aug 2018

Cited by 18 | Viewed by 9344

Abstract

Genome-level data can provide researchers with unprecedented precision to examine the causes and genetic consequences of population declines, which can inform conservation management. Here, we present a high-quality, long-read, de novo genome assembly for one of the world’s most endangered bird species, the [...] Read more.

Genome-level data can provide researchers with unprecedented precision to examine the causes and genetic consequences of population declines, which can inform conservation management. Here, we present a high-quality, long-read, de novo genome assembly for one of the world’s most endangered bird species, the ʻAlalā (Corvus hawaiiensis; Hawaiian crow). As the only remaining native crow species in Hawaiʻi, the ʻAlalā survived solely in a captive-breeding program from 2002 until 2016, at which point a long-term reintroduction program was initiated. The high-quality genome assembly was generated to lay the foundation for both comparative genomics studies and the development of population-level genomic tools that will aid conservation and recovery efforts. We illustrate how the quality of this assembly places it amongst the very best avian genomes assembled to date, comparable to intensively studied model systems. We describe the genome architecture in terms of repetitive elements and runs of homozygosity, and we show that compared with more outbred species, the ʻAlalā genome is substantially more homozygous. We also provide annotations for a subset of immunity genes that are likely to be important in conservation management, and we discuss how this genome is currently being used as a roadmap for downstream conservation applications. Full article

(This article belongs to the Special Issue Conservation Genetics and Genomics)

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19 pages, 683 KiB

Open AccessArticle

RNA Structure Elements Conserved between Mouse and 59 Other Vertebrates

by Bernhard C. Thiel, Roman Ochsenreiter, Veerendra P. Gadekar, Andrea Tanzer and Ivo L. Hofacker

Genes 2018, 9(8), 392; https://doi.org/10.3390/genes9080392 - 1 Aug 2018

Cited by 15 | Viewed by 5566

Abstract

In this work, we present a computational screen conducted for functional RNA structures, resulting in over 100,000 conserved RNA structure elements found in alignments of mouse (mm10) against 59 other vertebrates. We explicitly included masked repeat regions to explore the potential of transposable [...] Read more.

In this work, we present a computational screen conducted for functional RNA structures, resulting in over 100,000 conserved RNA structure elements found in alignments of mouse (mm10) against 59 other vertebrates. We explicitly included masked repeat regions to explore the potential of transposable elements and low-complexity regions to give rise to regulatory RNA elements. In our analysis pipeline, we implemented a four-step procedure: (i) we screened genome-wide alignments for potential structure elements using RNAz-2, (ii) realigned and refined candidate loci with LocARNA-P, (iii) scored candidates again with RNAz-2 in structure alignment mode, and (iv) searched for additional homologous loci in mouse genome that were not covered by genome alignments. The 3’-untranslated regions (3’-UTRs) of protein-coding genes and small noncoding RNAs are enriched for structures, while coding sequences are depleted. Repeat-associated loci make up about 95% of the homologous loci identified and are, as expected, predominantly found in intronic and intergenic regions. Nevertheless, we report the structure elements enriched in specific genome elements, such as 3’-UTRs and long noncoding RNAs (lncRNAs). We provide full access to our results via a custom UCSC genome browser trackhub freely available on our website (http://rna.tbi.univie.ac.at/trackhubs/#RNAz). Full article

(This article belongs to the Special Issue Computational Analysis of RNA Structure and Function)

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12 pages, 5079 KiB

Open AccessArticle

PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility

by Faruk Hadziselimovic, Gieri Cathomas, Gilvydas Verkauskas, Darius Dasevicius and Michael B. Stadler

Genes 2018, 9(8), 391; https://doi.org/10.3390/genes9080391 - 1 Aug 2018

Cited by 10 | Viewed by 4117

Abstract

There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia [...] Read more.

There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia are absent in high infertility risk (HIR) patients, who are treated with a gonadotropin-releasing hormone agonist (GnRHa) to significantly lower the risk of infertility. Despite its prevalence, little is known about the molecular events involved in cryptorchidism. Previously, we compared the transcriptomes of LIR versus HIR patients treated with and without hormones. Here, we interpreted data regarding members of the positive regulatory domain-containing (PRDM) family; some of which encoded histone methyltransferases that are important for reproduction. We found there were lower levels of PRDM1, PRDM6, PRDM9, PRDM13, and PRDM14 mRNA in the testes of HIR patients compared with LIR patients, and that PRDM7, PRDM9, PRDM12, and PRDM16 were significantly induced after GnRHa treatment. Furthermore, we observed PRDM9 protein staining in the cytoplasm of germ cells in the testes from LIR and HIR patients, indicating that the mRNA and protein levels corresponded. This result indicated that the curative hormonal therapy for cryptorchidism involved conserved chromatin modification enzymes. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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14 pages, 2784 KiB

Open AccessArticle

Analysis of Candidate Idarubicin Drug Resistance Genes in MOLT-3 Cells Using Exome Nuclear DNA

by Tomoyoshi Komiyama, Atsushi Ogura, Takehito Kajiwara, Yoshinori Okada and Hiroyuki Kobayashi

Genes 2018, 9(8), 390; https://doi.org/10.3390/genes9080390 - 1 Aug 2018

Cited by 2 | Viewed by 3766

Abstract

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations [...] Read more.

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations in MOLT-3/IDR and MOLT-3 using both Genome Analysis Toolkit (GATK) and SnpEff program. We found 8839 genes with specific mutations in MOLT-3/IDR and 1162 genes with accompanying amino acid mutations. The 1162 genes were identified by exome analysis of polymerase-related genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and, among these, we identified genes with amino acid changes. In resistant strains, LIG and helicase plurality genes showed amino-acid-related changes. An amino acid mutation was also confirmed in polymerase-associated genes. Gene ontology (GO) enrichment testing was performed, and lipid-related genes were selected from the results. Fluorescent activated cell sorting (FACS) was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The results showed that an IDR concentration of 0.5 μg/mL resulted in slow permeability in MOLT-3/IDR. This slow IDR permeability may be due to the effects of amino acid changes in polymerase- and lipid-associated genes. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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