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1.
Mol Genet Genomics ; 295(2): 505-514, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31897801

RESUMO

α-thalassemia is an inherited blood disorder commonly caused by deletions or point mutations involving one or both α-globin genes. Recent studies shed new light on the critical role of upstream enhancers multi-species conserved sequences (MCSs) in the ordered regulation of α-globin gene expression. Herein, we reported two unrelated probands with deletions in α-globin genes and MCSs, respectively. The proband from Family A is a compound heterozygote carrying a known α+ mutation (-α3.7) and a novel 60.2 kb deletion causing the absence of both α-globin genes. The proband from Family B, on the other hand, is a compound heterozygote with a known α0 mutation (--SEA) and a novel deletion involving only upstream regulatory elements MCS-R1, R2 and R3, while the α-globin genes remain intact. Notably, both these two patients suffered varied extent of anemia, indicating that the loss of enhancer elements could equally lead to reduced synthesis of α-globin. Upon these observations, we then confirmed the exact breakpoints of these two novel deletions using a targeted next-generation sequencing (NGS) previously established by our group, which may enable further elucidation of the rearrangement mechanisms on these deletions and functional dissection of MCSs. Taken together, our study reports a reliable NGS-based molecular screening approach for accurate identification of copy number variations (CNVs) in the α-globin cluster and the genetic diagnosis of these two probands may help to extend the spectrum of α-thalassemia mutations in Chinese population.


Assuntos
Elementos Alu/genética , Anemia/genética , alfa-Globinas/genética , Talassemia alfa/genética , Adulto , Anemia/sangue , Anemia/patologia , Variações do Número de Cópias de DNA/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica/genética , Linhagem , Mutação Puntual/genética , Deleção de Sequência/genética , Talassemia alfa/sangue , Talassemia alfa/patologia
2.
J Basic Microbiol ; 60(1): 82-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650621

RESUMO

Involvement of LaeA in various biological processes of filamentous fungi has been demonstrated. However, its role in Penicillium digitatum, the causal agent of citrus postharvest green mold, remains unclear. In this study, a ΔPdLaeA mutant was constructed using homologous recombination. The production of conidia by the ΔPdLaeA mutant was reduced by half compared with that of the wild-type strain. The sensitivity of the ΔPdLaeA mutant increased under alkaline conditions. The virulence assay revealed that PdLaeA was dispensable for the virulence of P. digitatum. Comparative transcriptome analysis revealed that the function loss of PdLaeA resulted in the reduced expression of several secondary metabolite gene clusters. In addition, expression of several key regulators of conidiation (BrlA, FlbA, FlbC, FlbD, and FluG) was also downregulated in the ΔPdLaeA mutant. In summary, the present work demonstrated that PdLaeA was involved in the regulation of SM biosynthesis, as well as the development and environmental adaptation of P. digitatum.


Assuntos
Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Penicillium/genética , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Citrus/microbiologia , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Família Multigênica/genética , Penicillium/crescimento & desenvolvimento , Penicillium/metabolismo , Penicillium/fisiologia , Deleção de Sequência , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/fisiologia , Fatores de Transcrição/genética , Virulência/genética
3.
J Surg Res ; 246: 113-122, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563831

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment. MATERIALS AND METHODS: Male C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3'-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes. RESULTS: Differentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization. CONCLUSIONS: Transcriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Microglia/patologia , Doenças do Sistema Nervoso/patologia , Transdução de Sinais/genética , Animais , Lesões Encefálicas Traumáticas/complicações , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Família Multigênica/genética , Doenças do Sistema Nervoso/etiologia , Plasticidade Neuronal/genética , Fatores de Tempo , Regulação para Cima
4.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 91-96, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31833535

RESUMO

Distamycin (DST) is a well-characterized DNA minor groove binder with antivirus activity and antitumor potency. Two separate gene clusters (a 28-kb cluster and a 7-kb cluster) have recently been identified to coordinately encode the biosynthetic machinery of DST in Streptomyces netropsis. Here we report a gene cassette, which is linked to the aforementioned smaller dst gene cluster and plays an important role in the self-resistance to DST in S. netropsis. This cassette consists of three uncharacterized genes that might be implicated in DNA replication/repair. Knockout of the cassette led to the decrease in the production of DST, while heterologous expression of part of the cassette in S. lividans made it become resistant to both DST and mitomycin C, another DNA-binding agent. More interestingly, homologs of these three genes were found in genomes of other actinomyces that produce DNA-binding antibiotics, suggesting that a novel common mechanism in addition to pumping may enable these strains to resist the cytotoxic metabolites they produced.


Assuntos
Antibacterianos/farmacologia , Reparo do DNA/genética , Replicação do DNA/genética , Distamicinas/farmacologia , Farmacorresistência Bacteriana/genética , Genes Bacterianos/genética , Streptomyces/genética , Antibacterianos/biossíntese , Células Cultivadas , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/farmacologia , Distamicinas/biossíntese , Escherichia coli/genética , Técnicas de Inativação de Genes , Mitomicina/farmacologia , Família Multigênica/genética , Streptomyces/efeitos dos fármacos , Streptomyces lividans/efeitos dos fármacos
5.
Sheng Wu Gong Cheng Xue Bao ; 35(10): 1889-1900, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31668036

RESUMO

Novel natural products have always been the most important sources for discovery of new drugs. Since the end of the 20th century, advances in genomics technology have contributed to decode and analyze numerous genomes, revealing remarkable potential for production of new natural products in organisms. However, this potential is hampered by laboratory culture conditions. Therefore, the integration of all these new advances is necessary to unveil these treasures, addressing the rise in resistance to antibiotics. In this review, we discuss the strategies of genome mining, inducing the expression of silent biosynthetic gene clusters and construction of biological chassis.


Assuntos
Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Genômica , Animais , Genoma/genética , Família Multigênica/genética
6.
Mol Immunol ; 116: 174-179, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31704500

RESUMO

We considered the possibility that the greater the distance between an immune receptor V and J, the more likely the V usage. Such a hypothesis is supported by results from mouse experiments. And, such a hypothesis is consistent with the fundamental nature of recombination and genomic distance: the further the distance, the greater the chance of a DNA break. Thus, we exploited the vast dataset of V and J recombination reads available for the human TRA gene, particularly from cancer and blood specimens, to assess the frequency of TRAV usage with respect to distance from the TRAJ cluster. Results indicated that, indeed, over the entire TRAV cluster, there is a greater chance of V usage the further the distance from the J cluster. These results do not address causation, and are not consistent for certain individual V gene segments, but the results do indicate that overall, the larger the distance between the V and J gene segment cluster, the more likely the appearance of at least a subset of TRAV segments, particularly among tumor infiltrating lymphocytes. With a similar approach, the distal TRAV gene segments were also found to be more commonly associated with a subset of distal TRAJ segments. These results have implications for restrictions on the apparent TRA repertoire in disease settings.


Assuntos
Família Multigênica/genética , Neoplasias/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Humanos , Linfócitos do Interstício Tumoral/imunologia , Família Multigênica/imunologia , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
7.
World J Microbiol Biotechnol ; 35(12): 189, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748890

RESUMO

Fossil fuels consumption impacts the greenhouse gas emissions. Biofuels are considered as alternative renewable energy sources to reduce the fossil fuels dependency. Bioethanol produced by recombinant microorganisms is a widely suggested alternative to increase the yield in fermentation processes. However, ethanol and acetate accumulation under the fermentation process had been described as important stressors for the metabolic capabilities of the microorganisms, stopping the fermentation process and affecting the ethanol yield. Ethanol tolerance is a determining factor in the improvement of fermentative properties of microorganisms; however understanding of ethanol tolerance is limited. The engineered Escherichia coli KO11 strain has been studied in detail and used as an ethanologenic bacteria model. The strain is capable of using glucose and xylose for an efficient ethanol yield. In the current work, the effect of the iron-sulfur cluster (ISC) over-expression in the KO11 strain, on its tolerance and ethanol yield, was evaluated. Fatty acids profiles of membrane phospholipids in the E. coli KO11 were modified under ethanol addition, but not due to the hscA mutation. The hscA mutation provoked a decrease in ethanol tolerance in the Kmp strain when was grown with 2% ethanol, in comparison to KO11 parent strain. Ethanol tolerance was improved in the mutant Kmp complemented with the recombinant isc gene cluster (pJC10 plasmid) from LD50 2.16% to LD50 3.8% ethanol. In batch fermentation on 1 L bioreactor using mineral medium with glucose (120 g/L), the KO11 strain showed ethanol production efficiencies of ~ 76.9%, while the hscA mutant (Kmp) ~ 75.4% and the transformed strain Kmp(pJC10) showed ~ 92.4% efficiency. Ethanol amount increase in the engineered Kmp(pJC10) strain was correlated with less organic acids (such as acetate and lactate) production in the fermentation medium (2.3 g/L), compared to that in the KO11 (17.05 g/L) and the Kmp (16.62 g/L). Alcohol dehydrogenase (ADH) activity was increased ~ 350% in the transformed Kmp(pJC10) strain, whereas in the Kmp mutant, the phosphoglycerate kinase (PGK), pyruvate kinase (PYK), and ADH activities were diminished, comparing to KO11. The results suggest that the isc system over-expression in the ethanologenic E. coli KO11 strain, increases ethanol yield mainly by improving ethanol tolerance and ADH activity, and by redirecting the metabolic flux from acetate synthesis to ethanol.


Assuntos
Ácidos/metabolismo , Tolerância a Medicamentos/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Etanol/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Família Multigênica/genética , Álcool Desidrogenase/genética , Técnicas de Cultura Celular por Lotes , Biocombustíveis , Reatores Biológicos , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Etanol/toxicidade , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Fermentação , Engenharia Genética , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas com Ferro-Enxofre/genética , Cinética , Redes e Vias Metabólicas/genética , Mutação , Xilose/metabolismo
8.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31570563

RESUMO

Bacteria use siderophores to scavenge iron from environmental or host sources. The iron acquisition systems of Chromobacterium violaceum, a ubiquitous environmental bacterium that can cause infections in humans, are still unknown. In this work, we demonstrated that C. violaceum produces putative distinct endogenous siderophores, here named chromobactin and viobactin, and showed that they are each required for iron uptake and virulence. An in silico analysis in the genome of C. violaceum revealed that genes related to synthesis and uptake of chromobactin (cba) and viobactin (vba) are located within two secondary-metabolite biosynthetic gene clusters. Using a combination of gene deletions and siderophore detection assays, we revealed that chromobactin and viobactin are catecholate siderophores synthesized from the common precursor 2,3-dihydroxybenzoate (2,3-DHB) on two nonribosomal peptide synthetase (NRPS) enzymes (CbaF and VbaF) and taken up by two TonB-dependent receptors (CbuA and VbuA). Infection assays in mice revealed that both the synthesis and the uptake of chromobactin or viobactin are required for the virulence of C. violaceum, since only the mutant strains that do not produce any siderophores or are unable to take up both of them were attenuated for virulence. In addition, the mutant strain unable to take up both siderophores showed a pronounced attenuation of virulence in vivo and reduced neutrophil extracellular trap (NET) formation in in vitro assays, suggesting that extracellularly accumulated siderophores modulate the host immune response. Overall, our results revealed that C. violaceum uses distinct endogenous siderophores for iron uptake and its establishment in the host.


Assuntos
Chromobacterium/genética , Chromobacterium/metabolismo , Ferro/metabolismo , Sideróforos/genética , Sideróforos/metabolismo , Animais , Transporte Biológico/fisiologia , Chromobacterium/patogenicidade , Armadilhas Extracelulares/metabolismo , Feminino , Hidroxibenzoatos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Família Multigênica/genética , Neutrófilos/metabolismo , Peptídeo Sintases/metabolismo
9.
Int J Mol Sci ; 20(20)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615135

RESUMO

The Dynamin gene family play a significance role in many physiological processes, especially ARC5 (Accumulation and replication of chloroplasts 5) in the process of plastid division. We performed a genome-wide analysis of the cassava Dynamin family based on the published cassava genome sequence and identified ARC5. 23 cassava Dynamins (MeDynamins) were identified and renamed. 23 MeDynamins were further divided into five major groups based on their structural and phylogenetic characteristics. The segmental duplication events have a significant impact on the expansion of MeDynamins. ARC5 expression analysis showed that there were differences between leaves and roots of cassava at different developmental stages. The tissue-specific expression analysis of the MeDynamins showed that most of MeDynamins were expressed in stem apical meristem and embryogenesis, whereas ARC5 was mainly expressed in leaves. The processing of IAA (Indole-3-acetic Acid) and MeJA (Methyl Jasmonate) verified the prediction results of cis-elements, and ACR5 was closely related to plant growth and positively correlated. It also indicated that high concentrations of MeJA treatment caused the cassava defense mechanism to function in advance. In conclusion, these findings provide basic insights for functional validation of the ARC5 genes in exogenous hormonal treatments.


Assuntos
Dinaminas/genética , Manihot/genética , Filogenia , Desenvolvimento Vegetal/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Cloroplastos/genética , Mapeamento Cromossômico , Regulação da Expressão Gênica de Plantas , Manihot/crescimento & desenvolvimento , Família Multigênica/genética , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento
10.
Nat Commun ; 10(1): 4574, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594929

RESUMO

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.


Assuntos
Archaea/genética , Evolução Biológica , Fontes Termais/microbiologia , Metagenoma , Oxirredutases/genética , Alcanos/metabolismo , Archaea/enzimologia , Archaea/isolamento & purificação , China , Biologia Computacional , Genoma Arqueal , Temperatura Alta , Redes e Vias Metabólicas/genética , Metano/metabolismo , Família Multigênica/genética , Oxirredutases/metabolismo , Filogenia
11.
PLoS Genet ; 15(9): e1008369, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525193

RESUMO

The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that utilizes read sequencing depth information to estimate Y ampliconic gene copy number per family. We applied this tool to whole-genome sequencing data of 149 men with matched testis expression data whose samples are part of the Genotype-Tissue Expression (GTEx) project. We found that the Y ampliconic gene families with low copy number in humans were deleted or pseudogenized in non-human great apes, suggesting relaxation of functional constraints. Among the Y ampliconic gene families, higher copy number leads to higher expression. Within the Y ampliconic gene families, copy number does not influence gene expression, rather a high tolerance for variation in gene expression was observed in testis of presumably healthy men. No differences in gene expression levels were found among major Y haplogroups. Age positively correlated with expression levels of the HSFY and PRY gene families in the African subhaplogroup E1b, but not in the European subhaplogroups R1b and I1. We also found that expression of five Y ampliconic gene families is coordinated with that of their non-Y (i.e. X or autosomal) homologs. Indeed, five ampliconic gene families had consistently lower expression levels when compared to their non-Y homologs suggesting dosage regulation, while the HSFY family had higher expression levels than its X homolog and thus lacked dosage regulation.


Assuntos
Cromossomos Humanos Y/genética , Genes Ligados ao Cromossomo Y/genética , Análise de Sequência de DNA/métodos , Animais , Cromossomos Humanos Y/fisiologia , Variações do Número de Cópias de DNA/genética , Bases de Dados Genéticas , Compensação de Dosagem (Genética)/genética , Compensação de Dosagem (Genética)/fisiologia , Epigênese Genética/genética , Dosagem de Genes/genética , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Genes Ligados ao Cromossomo Y/fisiologia , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Humanos , Masculino , Família Multigênica/genética , Testículo/metabolismo
12.
PLoS Genet ; 15(9): e1008400, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31553720

RESUMO

Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition. Auxin Response Factors (ARFs) Transcription Factors (TFs) that mediate auxin-dependent transcriptional changes are divided into A, B and C evolutive classes in land plants. The origin and nature of the first ARF proteins in algae is still debated. Here, we identify the most 'ancient' ARF homologue to date in the early divergent charophyte algae Chlorokybus atmophyticus, CaARF. Structural modelling combined with biochemical studies showed that CaARF already shares many features with modern ARFs: it is capable of oligomerization, interacts with the TOPLESS co-repressor and specifically binds Auxin Response Elements as dimer. In addition, CaARF possesses a DNA-binding specificity that differs from class A and B ARFs and that was maintained in class C ARF along plants evolution. Phylogenetic evidence together with CaARF biochemical properties indicate that the different classes of ARFs likely arose from an ancestral proto-ARF protein with class C-like features. The foundation of auxin signalling would have thus happened from a pre-existing hormone-independent transcriptional regulation together with the emergence of a functional hormone perception complex.


Assuntos
Carofíceas/genética , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Receptores de Superfície Celular/genética , Proteínas de Ligação a DNA/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas/genética , Família Multigênica/genética , Filogenia , Reguladores de Crescimento de Planta/genética , Elementos de Resposta/genética , Fatores de Transcrição/genética
13.
Mar Drugs ; 17(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480589

RESUMO

Identification and analysis of the whole genome of the marine-derived fungus Penicillium brasilianum HBU-136 revealed the presence of an interesting biosynthetic gene cluster (BGC) for non-ribosomal peptide synthetases (NRPS), highly homologous to the BGCs of indole-diketopiperazine derivatives. With the aid of genomic analysis, eight indole-diketopiperazines (1-8), including three new compounds, spirotryprostatin G (1), and cyclotryprostatins F and G (2 and 3), were obtained by large-scale cultivation of the fungal strain HBU-136 using rice medium with 1.0% MgCl2. The absolute configurations of 1-3 were determined by comparison of their experimental electronic circular dichroism (ECD) with calculated ECD spectra. Selective cytotoxicities were observed for compounds 1 and 4 against HL-60 cell line with the IC50 values of 6.0 and 7.9 µM, respectively, whereas 2, 3, and 5 against MCF-7 cell line with the IC50 values of 7.6, 10.8, and 5.1 µM, respectively.


Assuntos
Organismos Aquáticos/química , Dicetopiperazinas/química , Fungos/química , Fungos/genética , Indóis/química , Penicillium/química , Penicillium/genética , Organismos Aquáticos/genética , Linhagem Celular Tumoral , Dicroísmo Circular , Genoma/genética , Genômica , Células HL-60 , Humanos , Células MCF-7 , Família Multigênica/genética , Peptídeo Sintases/genética
14.
BMC Genomics ; 20(1): 696, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481022

RESUMO

BACKGROUND: Biosynthetic gene clusters produce a wide range of metabolites with activities that are of interest to the pharmaceutical industry. Specific interest is shown towards those metabolites that exhibit antimicrobial activities against multidrug-resistant bacteria that have become a global health threat. Genera of the phylum Firmicutes are frequently identified as sources of such metabolites, but the biosynthetic potential of its Virgibacillus genus is not known. Here, we used comparative genomic analysis to determine whether Virgibacillus strains isolated from the Red Sea mangrove mud in Rabigh Harbor Lagoon, Saudi Arabia, may be an attractive source of such novel antimicrobial agents. RESULTS: A comparative genomics analysis based on Virgibacillus dokdonensis Bac330, Virgibacillus sp. Bac332 and Virgibacillus halodenitrificans Bac324 (isolated from the Red Sea) and six other previously reported Virgibacillus strains was performed. Orthology analysis was used to determine the core genomes as well as the accessory genome of the nine Virgibacillus strains. The analysis shows that the Red Sea strain Virgibacillus sp. Bac332 has the highest number of unique genes and genomic islands compared to other genomes included in this study. Focusing on biosynthetic gene clusters, we show how marine isolates, including those from the Red Sea, are more enriched with nonribosomal peptides compared to the other Virgibacillus species. We also found that most nonribosomal peptide synthases identified in the Virgibacillus strains are part of genomic regions that are potentially horizontally transferred. CONCLUSIONS: The Red Sea Virgibacillus strains have a large number of biosynthetic genes in clusters that are not assigned to known products, indicating significant potential for the discovery of novel bioactive compounds. Also, having more modular synthetase units suggests that these strains are good candidates for experimental characterization of previously identified bioactive compounds as well. Future efforts will be directed towards establishing the properties of the potentially novel compounds encoded by the Red Sea specific trans-AT PKS/NRPS cluster and the type III PKS/NRPS cluster.


Assuntos
Mineração de Dados , Genômica , Família Multigênica/genética , Virgibacillus/genética , Virgibacillus/metabolismo , Genoma Bacteriano/genética , Ilhas Genômicas/genética , Ribossomos/metabolismo
15.
Int J Food Microbiol ; 309: 108332, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494483

RESUMO

Vibrio parahaemolyticus is a major food-borne pathogen. V. parahaemolyticus infections are associated with various serotypes; to date, 71 K-serogroups of V. parahaemolyticus have been determined based on capsular polysaccharide (CPS) diversity. In this study, the capsular polysaccharide gene clusters (CPSgcs) of 55 K-serogroups were identified by whole-genome sequencing and analysis. These CPSgcs exhibit a high level of genetic diversity. A microsphere-based suspension array (MSA) was established for the detection and identification of 55 V. parahaemolyticus K-serogroups based on CPSgc-specific genes. To evaluate our array, a double-blind test with 120 clinical isolates was carried out. In addition, an in silico K-serotyping system was established based on V. parahaemolyticus CPSgc-specific genes. This system was then used to examine 845 publicly available V. parahaemolyticus genomes; the results demonstrated that 813 isolates belong to one of 43 K-serogroups. Taken together, these results demonstrate that the molecular system developed in this study is suitable for rapid serotyping of V. parahaemolyticus isolates from environmental and clinical samples. In addition, the system could be applied to epidemiological investigations of this important food-borne pathogen.


Assuntos
Cápsulas Bacterianas/genética , Doenças Transmitidas por Alimentos/diagnóstico , Polissacarídeos Bacterianos/genética , Sorotipagem/métodos , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/imunologia , Cápsulas Bacterianas/imunologia , Método Duplo-Cego , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Família Multigênica/genética , Polissacarídeos Bacterianos/imunologia , Sorogrupo , Vibrioses/diagnóstico , Vibrio parahaemolyticus/classificação
16.
J Microbiol Biotechnol ; 29(10): 1570-1579, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474098

RESUMO

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in gα1Δ, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.


Assuntos
Família Multigênica , Policetídeos/metabolismo , Xylariales/genética , Vias Biossintéticas , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Endófitos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Perfilação da Expressão Gênica , Família Multigênica/genética , Mutação , Paclitaxel/biossíntese , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Policetídeos/química , Xylariales/química , Xylariales/metabolismo
17.
Genes Genet Syst ; 94(4): 141-149, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31474650

RESUMO

The vomeronasal organ (VNO) plays a key role in sensing pheromonal cues, which elicit innate responses and induce social and sexual behaviors. The vomeronasal receptor 1 genes, V1Rs, encode members of a pheromone receptor family that are mainly expressed in the VNO. Previous studies have revealed that the V1R family shows extraordinary variety among mammalian species owing to successive gene gains and losses. Because species-specific pheromonal interaction may facilitate species-specific reproductive behaviors, understanding the evolution of V1Rs in terms of their origin, repertoire and phylogeny should provide insight into the mechanisms of animal diversification. Here I summarize recent studies about the V1R family from its initial discovery in the rat genome to extensive comparative analyses among vertebrates. I further introduce our recent findings for V1Rs in a broad range of vertebrates, which reveal unexpected diversity as well as shared features common among lineages.


Assuntos
Evolução Molecular , Receptores de Feromonas/genética , Vertebrados/genética , Órgão Vomeronasal/metabolismo , Animais , Regulação da Expressão Gênica , Genoma/genética , Família Multigênica/genética , Feromônios , Filogenia , Análise de Sequência de DNA , Especificidade da Espécie
18.
Nucleic Acids Res ; 47(18): e110, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400112

RESUMO

Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.


Assuntos
Vias Biossintéticas/genética , Biologia Computacional/métodos , Mineração de Dados/métodos , Família Multigênica/genética , Aprendizado Profundo , Genoma , Genoma Bacteriano/genética
19.
Biomed Res Int ; 2019: 2957821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380415

RESUMO

Background: Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear. Methods: Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC. Results: Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients. Conclusion: MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Metalotioneína/genética , Neoplasias Gástricas/genética , Metilação de DNA/genética , Progressão da Doença , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Família Multigênica/genética , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
20.
BMC Genomics ; 20(1): 629, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375088

RESUMO

BACKGROUND: Vocal learning, the ability to learn to produce vocalizations through imitation, relies on specialized brain circuitry known in songbirds as the song system. While the connectivity and various physiological properties of this system have been characterized, the molecular genetic basis of neuronal excitability in song nuclei remains understudied. We have focused our efforts on examining voltage-gated ion channels to gain insight into electrophysiological and functional features of vocal nuclei. A previous investigation of potassium channel genes in zebra finches (Taeniopygia guttata) revealed evolutionary modifications unique to songbirds, as well as transcriptional specializations in the song system [Lovell PV, Carleton JB, Mello CV. BMC Genomics 14:470 2013]. Here, we expand this approach to sodium, calcium, and chloride channels along with their modulatory subunits using comparative genomics and gene expression analysis encompassing microarrays and in situ hybridization. RESULTS: We found 23 sodium, 38 calcium, and 33 chloride channel genes (HGNC-based classification) in the zebra finch genome, several of which were previously unannotated. We determined 15 genes are missing relative to mammals, including several genes (CLCAs, BEST2) linked to olfactory transduction. The majority of sodium and calcium but few chloride channels showed differential expression in the song system, among them SCN8A and CACNA1E in the direct motor pathway, and CACNG4 and RYR2 in the anterior forebrain pathway. In several cases, we noted a seemingly coordinated pattern across multiple nuclei (SCN1B, SCN3B, SCN4B, CACNB4) or sparse expression (SCN1A, CACNG5, CACNA1B). CONCLUSION: The gene families examined are highly conserved between avian and mammalian lineages. Several cases of differential expression likely support high-frequency and burst firing in specific song nuclei, whereas cases of sparse patterns of expression may contribute to the unique electrophysiological signatures of distinct cell populations. These observations lay the groundwork for manipulations to determine how ion channels contribute to the neuronal excitability properties of vocal learning systems.


Assuntos
Tentilhões/genética , Tentilhões/fisiologia , Genômica , Aprendizagem , Neurônios/citologia , Vocalização Animal/fisiologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Canais Iônicos/genética , Família Multigênica/genética , Sintenia
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