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1.
Medicine (Baltimore) ; 100(6): e24355, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578531

RESUMEN

BACKGROUND: Genetic polymorphisms in the 15q25 region have been associated with the risk of lung cancer (LC). However, studies have yielded conflicting results. METHODS: Searches were conducted in databases, including PubMed, EMbase, Web of Science, CNKI, and Wanfang, for case-control studies up to August 1, 2019. After retrieving eligible studies and data extraction, we calculated pooled odds ratios with 95% confidence intervals. In the meta-analysis, we included 32 publications with a total of 52,795 patients with LC and 97,493 control cases to evaluate the polymorphisms in the CHRNA5/A3/B4 gene cluster in the 15q25 region. RESULTS: Data of the meta-analysis showed a significantly increased risk of LC in the presence of genetic polymorphisms (rs1051730, rs16969968, rs8034191). In the smoking subgroup, the CHRNA3 rs1051730 polymorphism was found to contribute to LC risk using following 5 models: the allelic model, the homozygous model, the heterozygous model, the dominant model, and the recessive model. Thus, the rs1051730 polymorphism may modify LC susceptibility under the condition of smoking. Stratification studies for CHRNA5-rs8034191 showed that Caucasian groups with the wild-type genotype (C/C) may be susceptible to LC in all 5 models. No significant relationship between CHRNA3 rs6495309 or rs3743073 and LC susceptibility was found. However, Asians with the rs3743037 B-allele showed an obviously higher risk of LC susceptibility than the Caucasian population, observed via allelic, heterozygous, and dominant models. CONCLUSIONS: The 3 polymorphisms of rs1051730, rs16969968 and rs8034191 in the CHRNA5/A3/B4 gene cluster in the 15q25 region were associated with LC risk, which might be influenced by ethnicity and smoking status.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Neoplasias Pulmonares/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Nicotínicos/genética , Humanos , Neoplasias Pulmonares/etiología , Familia de Multigenes/genética , Factores de Riesgo
2.
Planta ; 253(3): 72, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33606144

RESUMEN

MAIN CONCLUSION: Comprehensive characterization of Gramineae HATs and HDACs reveals their conservation and variation. The recent WGD/SD gene pairs in the CBP and RPD/HDA1 gene family may confer specific adaptive evolutionary changes. Expression of OsHAT and OsHDAC genes provides a new vision in different aspects of development and response to diverse stress. The histone acetylase (HAT) and histone deacetylase (HDAC) have been proven to be tightly linked to play a crucial role in plant growth, development and response to abiotic stress by regulating histone acetylation levels. However, the evolutionary dynamics and functional differentiation of HATs and HDACs in Gramineae remain largely unclear. In the present study, we identified 37 HAT genes and 110 HDAC genes in seven Gramineae genomes by a detailed analysis. Phylogenetic trees of these HAT and HDAC proteins were constructed to illustrate evolutionary relationship in Gramineae. Gene structure, protein property and protein motif composition illustrated the conservation and variation of HATs and HDACs in Gramineae. Gene duplication analysis suggested that recent whole genome duplication (WGD)/segmental duplication (SD) events contributed to the diversification of the CBP and RPD3/HDA1 gene family in Gramineae. Furthermore, promoter cis-element prediction indicated that OsHATs and OsHDACs were likely functional proteins and involved in various signaling pathways. Expression analysis by RNA-seq data showed that all OsHAT and OsHDAC genes were expressed in different tissues or development stages, revealing that they were ubiquitously expressed. In addition, we found that their expression patterns were altered in response to cold, drought, salt, light, abscisic acid (ABA), and indole-3-acetic acid (IAA) treatments. These findings provide the basis for further identification of candidate OsHAT and OsHDAC genes that may be utilized in regulating growth and development and improving crop tolerance to abiotic stress.


Asunto(s)
Histona Acetiltransferasas/genética , Histona Desacetilasas/genética , Oryza/genética , Poaceae/genética , Estrés Fisiológico , Evolución Molecular , Duplicación de Gen , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Oryza/metabolismo , Filogenia , Proteínas de Plantas/genética
3.
Nat Commun ; 12(1): 685, 2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33514704

RESUMEN

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.


Asunto(s)
Abietanos/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Evolución Molecular , Proteínas de Plantas/genética , Salvia miltiorrhiza/enzimología , Abietanos/química , Ciclización , Sistema Enzimático del Citocromo P-450/metabolismo , Medicamentos Herbarios Chinos/química , Genes de Plantas/genética , Genoma de Planta , Familia de Multigenes/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Salvia miltiorrhiza/química , Salvia miltiorrhiza/genética
4.
Nat Commun ; 12(1): 678, 2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33514753

RESUMEN

Reprogramming complex cellular metabolism requires simultaneous regulation of multigene expression. Ex-situ cloning-based methods are commonly used, but the target gene number and combinatorial library size are severely limited by cloning and transformation efficiencies. In-situ methods such as multiplex automated genome engineering (MAGE) depends on high-efficiency transformation and incorporation of heterologous DNA donors, which are limited to few microorganisms. Here, we describe a Base Editor-Targeted and Template-free Expression Regulation (BETTER) method for simultaneously diversifying multigene expression. BETTER repurposes CRISPR-guided base editors and in-situ generates large numbers of genetic combinations of diverse ribosome binding sites, 5' untranslated regions, or promoters, without library construction, transformation, and incorporation of DNA donors. We apply BETTER to simultaneously regulate expression of up to ten genes in industrial and model microorganisms Corynebacterium glutamicum and Bacillus subtilis. Variants with improved xylose catabolism, glycerol catabolism, or lycopene biosynthesis are respectively obtained. This technology will be useful for large-scale fine-tuning of multigene expression in both genetically tractable and intractable microorganisms.


Asunto(s)
Edición Génica/métodos , Microbiología Industrial/métodos , Ingeniería Metabólica/métodos , Familia de Multigenes/genética , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sistemas CRISPR-Cas/genética , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , ADN Bacteriano/genética , Escherichia coli/genética , Genes Bacterianos/genética , Glicerol/metabolismo , Licopeno/metabolismo , Redes y Vías Metabólicas/genética , Transformación Bacteriana , Xilosa/metabolismo
5.
Food Chem ; 343: 128410, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33406573

RESUMEN

Monascus, which is traditionally used in various Asian industries, produces several secondary metabolites during the fermentation process, including citrinin, a toxin whose impact limits the development of the Monascus industry. We have previously found that the addition of 2.0 g/L genistein to Monascus medium reduces citrinin production by approximately 80%. Here, we explored the molecular mechanisms whereby genistein affects citrinin production. We sequenced the Monascus genome and performed transcriptome analysis on genistein-treated and -untreated groups. Comparison between the two groups showed 378 downregulated and 564 upregulated genes. Among the latter, we further examined the genes related to citrinin biosynthesis and quantified them using quantitative real-time polymerase chain reaction (qRT-PCR). Genes orf5, pksCT, orf3, orf1, orf6, and ctnE were significantly downregulated, demonstrating that genistein addition indeed affects citrinin synthesis. Our results may lay the groundwork for substantial improvements in the Monascus fermentation industry.


Asunto(s)
Citrinina/biosíntesis , Genisteína/farmacología , Monascus/química , Transcriptoma/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ontología de Genes , Genes Fúngicos , Monascus/genética , Monascus/metabolismo , Familia de Multigenes , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba/efectos de los fármacos
6.
Extremophiles ; 25(1): 61-76, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33415441

RESUMEN

The microbial H2-producing (hydrogenogenic) carbon monoxide (CO)-oxidizing activity by the membrane-associated CO dehydrogenase (CODH)/energy-converting hydrogenase (ECH) complex is an important metabolic process in the microbial community. However, the studies on hydrogenogenic carboxydotrophs had to rely on inherently cultivation and isolation methods due to their rare abundance, which was a bottleneck in ecological study. Here, we provided gene-targeted sequencing method for the diversity estimation of thermophilic hydrogenogenic carboxydotrophs. We designed six new degenerate primer pairs which effectively amplified the coding regions of CODH genes forming gene clusters with ECH genes (CODHech genes) in Firmicutes which includes major thermophilic hydrogenogenic carboxydotrophs in terrestrial thermal habitats. Amplicon sequencing by these primers using DNAs from terrestrial hydrothermal sediments and CO-gas-incubated samples specifically detected multiple CODH genes which were identical or phylogenetically related to the CODHech genes in Firmictes. Furthermore, we found that phylogenetically distinct CODHech genes were enriched in CO-gas-incubated samples, suggesting that our primers detected uncultured hydrogenogenic carboxydotrophs as well. The new CODH-targeted primers provided us with a fine-grained (~ 97.9% in nucleotide sequence identity) diversity analysis of thermophilic hydrogenogenic carboxydotrophs by amplicon sequencing and will bolster the ecological study of these microorganisms.


Asunto(s)
Aldehído Oxidorreductasas/genética , Monóxido de Carbono/metabolismo , Firmicutes/genética , Complejos Multienzimáticos/genética , Cartilla de ADN , Firmicutes/enzimología , Familia de Multigenes
7.
Nat Commun ; 12(1): 611, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33504776

RESUMEN

Genome sequences have been determined for many model organisms; however, repetitive regions such as centromeres, telomeres, and subtelomeres have not yet been sequenced completely. Here, we report the complete sequences of subtelomeric homologous (SH) regions of the fission yeast Schizosaccharomyces pombe. We overcame technical difficulties to obtain subtelomeric repetitive sequences by constructing strains that possess single SH regions of a standard laboratory strain. In addition, some natural isolates of S. pombe were analyzed using previous sequencing data. Whole sequences of SH regions revealed that each SH region consists of two distinct parts with mosaics of multiple common segments or blocks showing high variation among subtelomeres and strains. Subtelomere regions show relatively high frequency of nucleotide variations among strains compared with the other chromosomal regions. Furthermore, we identified subtelomeric RecQ-type helicase genes, tlh3 and tlh4, which add to the already known tlh1 and tlh2, and found that the tlh1-4 genes show high sequence variation with missense mutations, insertions, and deletions but no severe effects on their RNA expression. Our results indicate that SH sequences are highly polymorphic and hot spots for genome variation. These features of subtelomeres may have contributed to genome diversity and, conversely, various diseases.


Asunto(s)
Variación Genética , Genoma Fúngico , Schizosaccharomyces/genética , Telómero/genética , Secuencia de Bases , Mutación INDEL/genética , Mosaicismo , Familia de Multigenes , Nucleótidos/genética , Filogenia , ARN de Hongos/genética , RecQ Helicasas/genética , Schizosaccharomyces/aislamiento & purificación
8.
Nat Commun ; 12(1): 459, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33469030

RESUMEN

Some Bacteroidetes and other human colonic bacteria can degrade arabinoxylans, common polysaccharides found in dietary fiber. Previous work has identified gene clusters (polysaccharide-utilization loci, PULs) for degradation of simple arabinoxylans. However, the degradation of complex arabinoxylans (containing side chains such as ferulic acid, a phenolic compound) is poorly understood. Here, we identify a PUL that encodes multiple esterases for degradation of complex arabinoxylans in Bacteroides species. The PUL is specifically upregulated in the presence of complex arabinoxylans. We characterize some of the esterases biochemically and structurally, and show that they release ferulic acid from complex arabinoxylans. Growth of four different colonic Bacteroidetes members, including Bacteroides intestinalis, on complex arabinoxylans results in accumulation of ferulic acid, a compound known to have antioxidative and immunomodulatory properties.


Asunto(s)
Proteínas Bacterianas/metabolismo , Bacteroides/enzimología , Esterasas/metabolismo , Microbioma Gastrointestinal/fisiología , Xilanos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/ultraestructura , Bacteroides/genética , Colon/microbiología , Ácidos Cumáricos/metabolismo , Cristalografía por Rayos X , Fibras de la Dieta/metabolismo , Pruebas de Enzimas , Esterasas/genética , Esterasas/aislamiento & purificación , Esterasas/ultraestructura , Humanos , Mucosa Intestinal/microbiología , Simulación de Dinámica Molecular , Familia de Multigenes/genética , Especificidad por Sustrato , Xilanos/química
9.
Cell Prolif ; 54(2): e12978, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33393114

RESUMEN

OBJECTIVES: The final stage of liver development is the production of hepatocytes and cholangiocytes (biliary epithelial cells) from bipotent hepatic progenitor cells. We used HepaRG cells, which are bipotent and able to differentiate into both hepatocytes and cholangiocytes, as a model to study the action of a novel lncRNA (lnc-RHL) and its role in the regulation of bipotency leading to hepatocytes and cholangiocytes. MATERIALS AND METHODS: Differentiation of HepaRG cells was assessed by marker expression and morphology which revealed their ability to differentiate into hepatocytes and cholangiocytes (modelling the behaviour of hepatoblasts in vivo). Using a qRT-PCR and RACE, we cloned a novel lncRNA (lnc-RHL; regulator of hepatic lineages) that is upregulated upon HepaRG differentiation. Using inducible knockdown of lnc-RHL concurrently with differentiation, we show that lnc-RHL is required for proper HepaRG cell differentiation resulting in diminution of the hepatocyte lineage. RESULTS: Here, we report the discovery of lnc-RHL, a spliced and polyadenylated 670 base lncRNA expressed from the 11q23.3 apolipoprotein gene cluster. lnc-RHL expression is confined to hepatic lineages and is upregulated when bipotent HepaRG cells are caused to differentiate. HepaRG cells made deficient for lnc-RHL have reduced ability to differentiate into hepatocytes, but retain their ability to differentiate into cholangiocytes. CONCLUSIONS: Deficiency for lnc-RHL in HepaRG cells converts them from bipotent progenitor cells to unipotent progenitor cells with impaired ability to yield hepatocytes. We conclude that lnc-RHL is a key regulator of bipotency in HepaRG cells.


Asunto(s)
Diferenciación Celular/genética , Hepatocitos/metabolismo , ARN Largo no Codificante/metabolismo , Apolipoproteínas/genética , Apolipoproteínas/metabolismo , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula , Niño , Cromosomas Humanos Par 11 , Doxorrubicina/farmacología , Femenino , Células Hep G2 , Factor Nuclear 4 del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/metabolismo , Hepatocitos/citología , Humanos , Hígado/metabolismo , Masculino , Familia de Multigenes , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Células Madre/citología , Células Madre/metabolismo , Adulto Joven
10.
Plant Mol Biol ; 105(4-5): 527-541, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33387173

RESUMEN

KEY MESSAGE: This report shows detailed characterization of LOX gene family in sorghum and provides new insight of sorghum LOX genes in genetic structure and their roles in plant response to infestation by sugarcane aphids. Lipoxygenases (LOXs) are monomeric, nonheme iron-containing dioxygenases that initiate the fatty acid oxidation pathway creating oxylipins and plant hormone jasmonate both have a key role in plant development and defense. To date, a comprehensive and systematic analysis of sorghum LOXs is still deficient. Thus, we performed a genome-wide analysis of the sorghum LOXs genome and identified nine LOXs genes. Detailed examination of protein sequences and phylogenetic analysis categorized the sorghum LOXs into two subclasses, 9-LOXs (SbLOX1, SbLOX3, SbLOX4, SbLOXm, and SbLOXo), 13-LOXs (SbLOX9, SbLOX5, and SbLOX2), and the unclassified SbLOX8. This classification was further supported by sequence similarity/identity matrix and subcellular localization analysis. The lipoxygenase domains, motifs, and vital amino acids were highly conserved in all sorghum LOX genes. In silico analysis of the promoter region of SbLOXs identified different hormones responsive cis-elements. Furthermore, to explore the roles of sorghum LOXs during sugarcane aphid feeding and exogenous MeJA application, expression analysis was conducted for all the eight LOXs in resistant (Tx2783) and susceptible (Tx7000) sorghum lines, respectively. As detailed in this report, the data generated from both genome-wide identification and expression analysis of lipoxygenase genes suggest the putative functions of two 13-LOXs (SbLOX9 and SbLOX5) and three 9-LOXs (SbLOX1, SbLOX3, and SbLOXo) in biosynthesis of jasmonic acid, green leaf volatiles and death acids, and all of them are involved in defense-related functions in plants. Furthermore, this report represents the first genome-wide analysis of the LOX gene family in sorghum, which will facilitate future studies to characterize the roles of each individual LOXs gene in aphid resistance and defense responses to other stresses.


Asunto(s)
Genoma de Planta/genética , Estudio de Asociación del Genoma Completo/métodos , Lipooxigenasa/genética , Familia de Multigenes , Proteínas de Plantas/genética , Sorghum/genética , Secuencia de Aminoácidos , Animales , Áfidos/fisiología , Ciclopentanos/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Interacciones Huésped-Parásitos , Lipooxigenasa/clasificación , Lipooxigenasa/metabolismo , Oxilipinas/farmacología , Filogenia , Reguladores del Crecimiento de las Plantas/farmacología , Proteínas de Plantas/clasificación , Proteínas de Plantas/metabolismo , Sorghum/enzimología , Sorghum/parasitología
11.
Mol Genet Genomics ; 296(2): 299-312, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33386986

RESUMEN

Pseudomonas syringae pv. tabaci 6605 (Pta6605) is a causal agent of wildfire disease in host tobacco plants and is highly motile. Pta6605 has multiple clusters of chemotaxis genes including cheA, a gene encoding a histidine kinase, cheY, a gene encoding a response regulator, mcp, a gene for a methyl-accepting chemotaxis protein, as well as flagellar and pili biogenesis genes. However, only two major chemotaxis gene clusters, cluster I and cluster II, possess cheA and cheY. Deletion mutants of cheA or cheY were constructed to evaluate their possible role in Pta6605 chemotaxis and virulence. Motility tests and a chemotaxis assay to known attractant demonstrated that cheA2 and cheY2 mutants were unable to swarm and to perform chemotaxis, whereas cheA1 and cheY1 mutants retained chemotaxis ability almost equal to that of the wild-type (WT) strain. Although WT and cheY1 mutants of Pta6605 caused severe disease symptoms on host tobacco leaves, the cheA2 and cheY2 mutants did not, and symptom development with cheA1 depended on the inoculation method. These results indicate that chemotaxis genes located in cluster II are required for optimal chemotaxis and host plant infection by Pta6605 and that cluster I may partially contribute to these phenotypes.


Asunto(s)
Histidina Quinasa/genética , Proteínas Quimiotácticas Aceptoras de Metilo/genética , Pseudomonas aeruginosa/fisiología , Pseudomonas syringae/fisiología , Tabaco/microbiología , Quimiotaxis , Resistencia a la Enfermedad , Eliminación de Gen , Histidina Quinasa/metabolismo , Proteínas Quimiotácticas Aceptoras de Metilo/metabolismo , Familia de Multigenes , Filogenia , Enfermedades de las Plantas/microbiología , Pseudomonas aeruginosa/patogenicidad , Pseudomonas syringae/patogenicidad , Virulencia
12.
Mol Genet Genomics ; 296(2): 355-368, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33438049

RESUMEN

Cellulose synthases (CesAs) are multi-subunit enzymes found on the plasma membrane of plant cells and play a pivotal role in cellulose production. The cotton fiber is mainly composed of cellulose, and the genetic relationships between CesA genes and cotton fiber yield and quality are not fully understood. Through a phylogenetic analysis, the CesA gene family in diploid Gossypium arboreum and Gossypium raimondii, as well as tetraploid Gossypium hirsutum ('TM-1') and Gossypium barbadense ('Hai-7124' and '3-79'), was divided into 6 groups and 15 sub-groups, with each group containing two to five homologous genes. Most CesA genes in the four species are highly collinear. Among the five cotton genomes, 440 and 1929 single nucleotide polymorphisms (SNPs) in the CesA gene family were identified in exons and introns, respectively, including 174 SNPs resulting in amino acid changes. In total, 484 homeologous SNPs between the A and D genomes were identified in diploids, while 142 SNPs were detected between the two tetraploids, with 32 and 82 SNPs existing within G. hirsutum and G. barbadense, respectively. Additionally, 74 quantitative trait loci near 18 GhCesA genes were associated with fiber quality. One to four GhCesA genes were differentially expressed (DE) in ovules at 0 and 3 days post anthesis (DPA) between two backcross inbred lines having different fiber lengths, but no DE genes were identified between these lines in developing fibers at 10 DPA. Twenty-seven SNPs in above DE CesA genes were detected among seven cotton lines, including one SNP in Ghi_A08G03061 that was detected in four G. hirsutum genotypes. This study provides the first comprehensive characterization of the cotton CesA gene family, which may play important roles in determining cotton fiber quality.


Asunto(s)
Glucosiltransferasas/genética , Gossypium/crecimiento & desarrollo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Mapeo Cromosómico , Fibra de Algodón , Diploidia , Regulación de la Expresión Génica de las Plantas , Genotipo , Gossypium/clasificación , Gossypium/genética , Familia de Multigenes , Filogenia , Fitomejoramiento , Proteínas de Plantas/genética , Poliploidía
13.
Mol Genet Genomics ; 296(2): 437-456, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33507381

RESUMEN

Wolbachia is an obligate intracellular bacterium that has undergone extensive genomic streamlining in its arthropod and nematode hosts. Because the gene encoding the bacterial DNA recombination/repair protein RecA is not essential in Escherichia coli, abundant expression of this protein in a mosquito cell line persistently infected with Wolbachia strain wStri was unexpected. However, RecA's role in the lytic cycle of bacteriophage lambda provides an explanation for retention of recA in strains known to encode lambda-like WO prophages. To examine DNA recombination/repair capacities in Wolbachia, a systematic examination of RecA and related proteins in complete or nearly complete Wolbachia genomes from supergroups A, B, C, D, E, F, J and S was undertaken. Genes encoding proteins including RecA, RecF, RecO, RecR, RecG and Holliday junction resolvases RuvA, RuvB and RuvC are uniformly absent from Wolbachia in supergroup C and have reduced representation in supergroups D and J, suggesting that recombination and repair activities are compromised in nematode-associated Wolbachia, relative to strains that infect arthropods. An exception is filarial Wolbachia strain wMhie, assigned to supergroup F, which occurs in a nematode host from a poikilothermic lizard. Genes encoding LexA and error-prone polymerases are absent from all Wolbachia genomes, suggesting that the SOS functions induced by RecA-mediated activation of LexA do not occur, despite retention of genes encoding a few proteins that respond to LexA induction in E. coli. Three independent E. coli accessions converge on a single Wolbachia UvrD helicase, which interacts with mismatch repair proteins MutS and MutL, encoded in nearly all Wolbachia genomes. With the exception of MutL, which has been mapped to a eukaryotic association module in Phage WO, proteins involved in recombination/repair are uniformly represented by single protein annotations. Putative phage-encoded MutL proteins are restricted to Wolbachia supergroups A and B and show higher amino acid identity than chromosomally encoded MutL orthologs. This analysis underscores differences between nematode and arthropod-associated Wolbachia and describes aspects of DNA metabolism that potentially impact development of procedures for transformation and genetic manipulation of Wolbachia.


Asunto(s)
Artrópodos/microbiología , Reparación del ADN , Nematodos/microbiología , Rec A Recombinasas/genética , Wolbachia/genética , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Especificidad del Huésped , Familia de Multigenes , Rec A Recombinasas/metabolismo , Recombinación Genética , Serina Endopeptidasas/genética , Especificidad de la Especie , Wolbachia/clasificación , Wolbachia/metabolismo
14.
J Autoimmun ; 117: 102595, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33453462

RESUMEN

BACKGROUND: Genetic variation at a multigene cluster at chromosome 3p21.31 and the ABO blood group have been associated with the risk of developing severe COVID-19, but the mechanism remains unclear. Complement activation has been associated with COVID-19 severity. OBJECTIVE: The aim of this study was to examine whether chromosome 3p21.31 and the ABO variants are linked to the activation of the complement cascade in COVID-19 patients. METHODS: We considered 72 unrelated European hospitalized patients with genetic data and evaluation of circulating C5a and soluble terminal complement complex C5b-9 (SC5b-9). Twenty-six (36.1%) patients carried the rs11385942 G>GA variant and 44 (66.1%) non-O blood group associated with increased risk of severe COVID-19. RESULTS: C5a and SC5-b9 plasma levels were higher in rs11385949 GA carriers than in non-carriers (P = 0.041 and P = 0.012, respectively), while C5a levels were higher in non-O group than in O group patients (P = 0.019). The association between rs11385949 and SC5b-9 remained significant after adjustment for ABO and disease severity (P = 0.004) and further correction for C5a (P = 0.018). There was a direct relationship between upper airways viral load and SC5b-9 in carriers of the rs11385949 risk allele (P = 0.032), which was not observed in non-carriers. CONCLUSIONS: The rs11385949 G>GA variant, tagging the chromosome 3 gene cluster variation and predisposing to severe COVID-19, is associated with enhanced complement activation, both with C5a and terminal complement complex, while non-O blood group with C5a levels. These findings provide a link between genetic susceptibility to more severe COVID-19 and complement activation.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Cromosomas Humanos Par 3/genética , Activación de Complemento/genética , Grupo de Ascendencia Continental Europea , Genotipo , Familia de Multigenes/genética , Anciano , Complemento C5a/genética , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Carga Viral
15.
Nucleic Acids Res ; 49(2): 986-1005, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33398323

RESUMEN

Extracytoplasmic function σ factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As a result, we identified an average of ∼10 ECFs per bacterial genome and 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands previous classification efforts ∼50-fold, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences and an openly accessible data repository called 'ECF Hub' (https://www.computational.bio.uni-giessen.de/ecfhub), will serve as a powerful hypothesis-generator to guide future research in the field.


Asunto(s)
Proteínas Bacterianas/química , Familia de Multigenes , Factor sigma/clasificación , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Secuencia de Consenso , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/metabolismo , Regulación Bacteriana de la Expresión Génica , Filogenia , Alineación de Secuencia , Factor sigma/genética , Transducción de Señal , Especificidad por Sustrato , Terminología como Asunto
16.
Ecotoxicol Environ Saf ; 208: 111661, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396171

RESUMEN

NRAMP family genes participate in the absorption and transport of heavy metals such as cadmium (Cd), zinc (Zn), copper (Cu), lead (Pb), iron (Fe) and manganese (Mn) and play an important role in the response to heavy metal stress. There is an abundance of research on these genes in bacteria, plants and fungi, although not in S. tuberosum. A total of 48 members(potato(5), Arabidopsis(7), Tomato(9), pepper(9), rice(12) and tobacco(6)) were identified from 6 species (potato (Solanum tuberosum), Arabidopsis thaliana, Tomato (Solanum lycopersicum), pepper (Capsicum annuum), rice (Oryza sativa) and tobacco (Nicotiana attenuate)) and were classified into four subgroups. Across NRAMP gene family members, there are 15 highly conserved motifs that have similar genetic structures and characteristics. In addition, a total of 16 pairs of colinear genes were found in eight species. Analysis of cis-elements indicated that, in response to abiotic stress, NRAMPs are mainly regulated by phytohormones and transcription factors. In addition, analysis of expression profiles indicated that StNRAMP4 is mainly expressed in the roots. According to a qRT-PCR-based analysis of the StNRAMP family, with the exception of Pb2+ stress, StNRAMPs positively responded to stress from Cu2+, Cd2+, Zn2+ and Ni2+ and The expression patterns is similar of StNRAMP2, under Pb2+, and Cu2+ treatment, the relative expression peaked at 24 h. the relative expression peaked at 12 h and was upregulated 428-fold in the roots under Ni2+ stress. Under Cd2+ stress, StNRAMP3 was upregulated 28-fold in the leaves. StNRAMP1, StNRAMP4 and StNRAMP5 showed significant upregulation under Cu2+, Cd2+ and Zn2+ stress, respectively. Expression of StNRAMPs could be specifically induced by heavy metals, implying their possible role in the transport and absorption of heavy metals. This research explains the colinear characteristics of NRAMPs in several food crop species, which is useful for providing important genetic resources for cultivating food crop that accumulate low amounts of heavy metals and for explaining the biological functions of NRAMPs in plants.


Asunto(s)
Metales Pesados/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum tuberosum/fisiología , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Genoma de Planta/genética , Familia de Multigenes , Elementos Reguladores de la Transcripción , Solanum tuberosum/genética , Solanum tuberosum/metabolismo
17.
Gene ; 770: 145348, 2021 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-33333230

RESUMEN

Heat shock factors (Hsfs) and heat shock proteins (Hsps) play a critical role in the molecular mechanisms such as plant development and defense against abiotic. As an important food crop, maize is vulnerable to adverse environment such as heat stress and water logging, which leads to a decline in yield and quality. To date, very little is known regarding the structure and function of Hsf and Hsp genes in maize. Although some Hsf and Hsp genes have been characterized in maize, analysis of the entire Hsf and Hsp70 gene families were not completed following Maize (B73) Genome Sequencing Project. Therefore, studying their molecular mechanism and revealing their biological function in plant stress resistance process will contribute to reveal important theoretical significance and application value for improving corn yield and quality. In this study, we have identified 25 ZmHsf and 22 ZmHsp70 genes in maize. The structural characteristics and phylogenetic relationships of the Hsf and Hsp70 gene families of Arabidopsis thaliana, rice and maize were compared. The final 25 ZmHsf proteins and 22 ZmHsp70 proteins were divided into three and four subfamilies, respectively. In addition, chromosomal localization indicated that the ZmHsf and ZmHsp70 genes were unevenly distributed on the chromosome, and the gene structure map revealed the characteristics of their structures. Finally, transcriptome analysis indicated that most of the ZmHsf and ZmHsp70 genes showed different expression patterns at different developmental stages of maize. Further, by semi-quantitative RT-PCR and quantitative real-time PCR analysis, all 25 ZmHsf and 22 ZmHsp70 genes were confirmed to respond to heat stress treatment, indicating that they have potential effects in heat stress response. The analyses performed by combining co-expression network with protein-protein interaction network among the members of the Hsf and Hsp70 gene families in maize further enabled us to recognize components involved in the regulatory network associated with hsfs and hsp70s complex. The predicted subcellular location revealed that maize Hsp70 proteins exhibited a various subcellular distribution, which may be associated with functional diversification in heat stress response. Taken together, our study provides comprehensive information on the members of Hsf and Hsp70 gene families and will help in elucidating their exact function in maize.


Asunto(s)
Cromosomas de las Plantas , Regulación de la Expresión Génica de las Plantas/fisiología , Proteínas HSP70 de Choque Térmico , Familia de Multigenes/fisiología , Proteínas de Plantas , Zea mays , Cromosomas de las Plantas/genética , Cromosomas de las Plantas/metabolismo , Estudio de Asociación del Genoma Completo , Proteínas HSP70 de Choque Térmico/biosíntesis , Proteínas HSP70 de Choque Térmico/genética , Proteínas de Plantas/biosíntesis , Proteínas de Plantas/genética , Zea mays/genética , Zea mays/metabolismo
18.
Gene ; 764: 145094, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32860898

RESUMEN

Long chain acyl-CoA synthetases (ACSLs), which drive the conversion of long chain fatty acid into acyl-CoA, an ingredient of lipid synthesis, have been well-acknowledged to exert an indispensable role in many metabolic processes in mammals, especially lipid metabolism. However, in chicken, the evolutionary characteristics, expression profiles and regulatory mechanisms of ACSL gene family are rarely understood. Here, we analyzed the genomic synteny, gene structure, evolutionary event and functional domains of the ACSL gene family members using bioinformatics methods. The spatiotemporal expression profiles of ACSL gene family, and their regulatory mechanism were investigated via bioinformatics analysis incorporated with in vivo and in vitro estrogen-treated experiments. Our results indicated that ACSL2 gene was indeed evolutionarily lost in the genome of chicken. Chicken ACSLs shared an AMP-binding functional domain, as well as highly conversed ATP/AMP and FACS signature motifs, and were clustered into two clades, ACSL1/5/6 and ACSL3/4, based on high sequence similarity, similar gene features and conversed motifs. Chicken ACSLs showed differential tissue expression distributions, wherein the significantly decreased expression level of ACSL1 and the significantly increased expression level of ACSL5 were found, respectively, the expression levels of the other ACSL members remained unchanged in the liver of peak-laying hens versus pre-laying hens. Moreover, the transcription activity of ACSL1, ACSL3 and ACSL4 was silenced and ACSL6 was activated by estrogen, but no response to ACSL5. In conclusion, though having highly conversed functional domains, chicken ACSL gene family is organized into two separate groups, ACSL1/5/6 and ACSL3/4, and exhibits varying expression profiles and estrogen effects. These results not only pave the way for better understanding the specific functions of ACSL genes in avian lipid metabolism, but also provide a valuable evidence for gene family characteristics.


Asunto(s)
Pollos/genética , Coenzima A Ligasas/genética , Evolución Molecular , Metabolismo de los Lípidos/genética , Familia de Multigenes/genética , Acilcoenzima A/metabolismo , Animales , Células Cultivadas , Embrión de Pollo , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Coenzima A Ligasas/metabolismo , Biología Computacional , Estrógenos/metabolismo , Ácidos Grasos/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Hepatocitos , Cultivo Primario de Células , Dominios Proteicos/genética , Análisis Espacio-Temporal , Sintenía
19.
Gene ; 766: 145156, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32949696

RESUMEN

Plant Glycogen Synthase Kinase 3 (GSK3)/SHAGGY-like kinase (GSK) proteins play important roles in modulating growth, development, and stress responses in several plant species. However, little is known about the members of the potato GSK (StGSK) family. Here, nine StGSK genes were identified and phylogenetically grouped into four clades. Gene duplication analysis revealed that segmental duplication contributed to the expansion of the StGSK family. Gene structure and motif pattern analyses indicated that similar exon/intron and motif organizations were found in StGSKs from the same clade. Conserved motif and kinase activity analyses indicated that the StGSKs encode active protein kinases, and they were shown to be distributed throughout whole cells. Cis-acting regulatory element analysis revealed the presence of many growth-, hormone-, and stress-responsive elements within the promoter regions of the StGSKs, which is consistent with their expression in different organs, and their altered expression in response to hormone and stress treatments. Association network analysis indicated that various proteins, including two confirmed BES1 family transcription factors, potentially interact with StGSKs. Overexpression of StSK21 provides enhanced sensitivity to salt stress in Arabidopsis thaliana plants. Overall, these results reveal that StGSK proteins are active protein kinases with purported functions in regulating growth, development, and stress responses.


Asunto(s)
Regulación de la Expresión Génica de las Plantas/genética , Genes de Plantas/genética , Familia de Multigenes/genética , Proteínas de Plantas/genética , Estrés Salino/genética , Solanum tuberosum/genética , Estrés Fisiológico/genética , Arabidopsis/genética , Cromosomas de las Plantas/genética , Duplicación de Gen/genética , Perfilación de la Expresión Génica/métodos , Estudio de Asociación del Genoma Completo/métodos , Filogenia , Reguladores del Crecimiento de las Plantas/genética , Factores de Transcripción/genética
20.
Mol Phylogenet Evol ; 154: 106965, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32956800

RESUMEN

A new paradigm has slowly emerged regarding the diversification of bryophytes, with inferences from molecular data highlighting a dynamic evolution of their genome. However, comparative studies of expressed genes among closely related taxa is so far missing. Here we contrast the dimensions of the vegetative transcriptome of Funaria hygrometrica and Physcomitrium pyriforme against the genome of their relative, Physcomitrium (Physcomitrella) patens. These three species of Funariaceae share highly conserved vegetative bodies, and are partially sympatric, growing on mineral soil in mostly temperate regions. We analyzed the vegetative gametophytic transcriptome of F. hygrometrica and P. pyriforme and mapped short reads, transcripts, and proteins to the genome and gene space of P. patens. Only about half of the transcripts of F. hygrometrica map to their ortholog in P. patens, whereas at least 90% of those of P. pyriforme align to loci in P. patens. Such divergence is unexpected given the high morphological similarity of the gametophyte but reflects the estimated times of divergence of F. hygrometrica and P. pyriforme from P. patens, namely 55 and 20 mya, respectively. The newly sampled transcriptomes bear signatures of at least one, rather ancient, whole genome duplication (WGD), which may be shared with one reported for P. patens. The transcriptomes of F. hygrometrica and P. pyriforme reveal significant contractions or expansions of different gene families. While transcriptomes offer only an incomplete estimate of the gene space, the high number of transcripts obtained suggest a significant divergence in gene sequences, and gene number among the three species, indicative of a rather strong, dynamic genome evolution, shaped in part by whole, partial or localized genome duplication. The gene ontology of their specific and rapidly-evolving protein families, suggests that the evolution of the Funariaceae may have been driven by the diversification of metabolic genes that may optimize the adaptations to environmental conditions, a hypothesis well in line with ecological patterns in the genetic diversity and structure in seed plants.


Asunto(s)
Bryopsida/anatomía & histología , Bryopsida/genética , Filogenia , Evolución Molecular , Genoma de Planta , Familia de Multigenes , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma/genética
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