Genome, Helminth

  • 文章类型: Journal Article
    染色体(SMC)复合物的结构维持-粘附素和凝集素-对于细胞分裂过程中的染色体分离和压缩至关重要。在中间阶段,哺乳动物粘附素还将基因组折叠成环和域。在这里我们展示,在秀丽隐杆线虫中,具有全中心染色体的物种,凝集素I是主要的,远程环路挤出机。凝缩素I及其X特异性变体的丢失,凝集素IDC,导致全基因组分解,X特异性拓扑关联域的染色体混合和消失,同时加强精细尺度的表观基因组区室。此外,凝缩素I/IDC失活导致X连锁基因的上调,并揭示了将凝缩素IDC的X靶向负载复合物的结合位点聚集在一起的核体。C.elegans凝集素I/IDC因此独特地组织全中心间期染色体,类似于哺乳动物中的粘菌素,以及调节X染色体基因表达。
    The structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin IDC, leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/IDC inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin IDC. C. elegans condensin I/IDC thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.
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  • 文章类型: Journal Article
    Dirofilariaimmitis是一种具有兽医学意义的丝虫寄生线虫。随着耐药菌株在美国的出现,必须确定在世界其他地区发生抵抗的可能性。一种方法是在广泛的地理范围内进行群体遗传研究,并对单个蠕虫的基因组进行测序,以了解与抗性相关的全基因组遗传变异。与从宿主心脏中提取成年阶段相比,在宿主血液中发现的D.immitis的未成熟生命阶段对样品更容易接近且侵入性较小。为了评估未成熟生命阶段在群体遗传分析中的使用,我们对从狗血中分离的9个(n=9)个个体D.immitismicrofilaria样本进行了全基因组扩增和全基因组测序。平均而言,与每个D.immitis基因组(核,线粒体,和Wolbachia内共生体)。对于狗的基因组,平均超过99%的映射读段与核基因组对齐,不到1%与线粒体基因组对齐。所有D.immitis基因组和狗核基因组的平均覆盖率小于1,而狗线粒体基因组的平均覆盖率为2.87。映射到狗宿主基因组的测序读段的压倒性比例可归因于微丝虫样品中残留的狗血细胞。这些结果证明了对个体未成熟寄生虫生命阶段进行全基因组研究的挑战,特别是在外来宿主DNA的存在下。
    Dirofilaria immitis is a filarial parasitic nematode of veterinary significance. With the emergence of drug-resistant isolates in the USA, it is imperative to determine the likelihood of resistance occurring in other regions of the world. One approach is to conduct population genetic studies across an extensive geographical range, and to sequence the genomes of individual worms to understand genome-wide genetic variation associated with resistance. The immature life stages of D. immitis found in the host blood are more accessible and less invasive to sample compared to extracting adult stages from the host heart. To assess the use of immature life stages for population genetic analyses, we have performed whole genome amplification and whole-genome sequencing on nine (n = 9) individual D. immitis microfilaria samples isolated from dog blood. On average, less than 1% of mapped reads aligned to each D. immitis genome (nuclear, mitochondrial, and Wolbachia endosymbiont). For the dog genome, an average of over 99% of mapped reads aligned to the nuclear genome and less than 1% aligned to the mitochondrial genome. The average coverage for all D. immitis genomes and the dog nuclear genome was less than 1, while the dog mitochondrial genome had an average coverage of 2.87. The overwhelming proportion of sequencing reads mapping to the dog host genome can be attributed to residual dog blood cells in the microfilariae samples. These results demonstrate the challenges of conducting genome-wide studies on individual immature parasite life stages, particularly in the presence of extraneous host DNA.
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  • 文章类型: Journal Article
    吸虫感染是经常被忽视的热带疾病之一,尽管它们在全球范围内普遍存在,并且具有寄生多种宿主物种和组织的显着能力。此外,这些寄生虫拥有重要的社会经济,medical,兽医和农业影响。在过去的几十年里,在弥合各种“omic”工具的信息差距方面已经取得了长足的进步,如蛋白质组学和基因组学,在这个领域。在这本书的版本中,我们重点介绍了有关吸虫的基因组学和蛋白质组学的最新进展,并特别关注了过去5年的进展。此外,我们提供了对研究吸虫生物学所采用的尖端技术的见解,并阐明了探索这种特殊寄生蠕虫的分子方面的可用资源。
    Trematode infections stand out as one of the frequently overlooked tropical diseases, despite their wide global prevalence and remarkable capacity to parasitize diverse host species and tissues. Furthermore, these parasites hold significant socio-economic, medical, veterinary and agricultural implications. Over the past decades, substantial strides have been taken to bridge the information gap concerning various \"omic\" tools, such as proteomics and genomics, in this field. In this edition of the book, we highlight recent progress in genomics and proteomics concerning trematodes with a particular focus on the advances made in the past 5 years. Additionally, we present insights into cutting-edge technologies employed in studying trematode biology and shed light on the available resources for exploring the molecular facets of this particular group of parasitic helminths.
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  • 文章类型: Journal Article
    旋毛虫属线虫是人类和动物的重要病原体。本研究旨在增强假螺旋藻(非包封表型)和螺旋藻(包封表型)的基因组和转录组资源,并探索转录谱。首先,我们改进了假螺旋藻(代码ISS13)和螺旋藻(代码ISS534)基因组的组装,实现56.6Mb的基因组大小(320个支架,N50为1.02Mb)和63.5Mb(568个脚手架,N50值为0.44Mb),分别。然后,对于每个物种,我们产生了三个关键发育阶段的RNA序列数据(第一阶段肌肉幼虫[L1s],成年人,和新生幼虫[NBLs];每个阶段重复三次),分析了阶段之间的差异转录,探索物种之间丰富的路径和过程。阶段特异性上调与细胞过程有关,新陈代谢,和宿主-寄生虫相互作用,和途径富集分析显示了物种之间独特的生物过程和细胞定位。的确,分泌的分子钙调蛋白,钙网蛋白,和calsyntenin-可能在调节宿主免疫反应和促进寄生虫存活中起作用-是假螺旋藻特有的,在螺旋藻中未检测到。这些对旋毛虫与宿主相互作用的分子机制的见解可能为开发针对旋毛虫病的新干预措施提供可能的途径。
    Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host-parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin-with possible roles in modulating host immune responses and facilitating parasite survival-were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella-host interactions might offer possible avenues for developing new interventions against trichinellosis.
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  • 文章类型: Journal Article
    桔梗,也被称为扁虫,是一个因其寄生代表而臭名昭著的双边无脊椎动物门。Cestoda班,Monogenea,而雷马塔包括寄生蠕虫,居住在多个寄主中,包括鱼类,人类,牲畜,并对人类健康造成巨大的经济损失和负担。和其他动物一样,扁虫的基因组有各种各样的旁系同源物,通过复制相关的基因,其起源可以在整个门的进化过程中绘制。通过硅分析,我们研究了inparalogs,即,特定物种的重复,专注于它们的生物学功能,表达式更改,和进化率。这些基因被认为是物种适应每个特定生态位的关键参与者。我们的结果表明,与特定功能术语相关的基因,比如对压力的反应,转移酶活性,氧化还原酶活性,和肽酶,在inparalogs中代表过多。这种趋势在不同类别的物种之间是保守的,包括自由生活的物种。来自曼氏血吸虫的可用表达数据,吸虫类的寄生虫,表现出内在同源物之间表达模式的高度保守性,但除了值得注意的例外,这也显示了快速进化的证据。我们讨论了自然选择如何操作以维持这些基因以及更适合观察的特定复制模型。我们的工作支持基因复制在扁虫进化中的关键作用,代表了该组中在全基因组水平上对同源物进化的首次研究。
    Platyhelminthes, also known as flatworms, is a phylum of bilaterian invertebrates infamous for their parasitic representatives. The classes Cestoda, Monogenea, and Trematoda comprise parasitic helminths inhabiting multiple hosts, including fishes, humans, and livestock, and are responsible for considerable economic damage and burden on human health. As in other animals, the genomes of flatworms have a wide variety of paralogs, genes related via duplication, whose origins could be mapped throughout the evolution of the phylum. Through in-silico analysis, we studied inparalogs, i.e., species-specific duplications, focusing on their biological functions, expression changes, and evolutionary rate. These genes are thought to be key players in the adaptation process of species to each particular niche. Our results showed that genes related with specific functional terms, such as response to stress, transferase activity, oxidoreductase activity, and peptidases, are overrepresented among inparalogs. This trend is conserved among species from different classes, including free-living species. Available expression data from Schistosoma mansoni, a parasite from the trematode class, demonstrated high conservation of expression patterns between inparalogs, but with notable exceptions, which also display evidence of rapid evolution. We discuss how natural selection may operate to maintain these genes and the particular duplication models that fit better to the observations. Our work supports the critical role of gene duplication in the evolution of flatworms, representing the first study of inparalogs evolution at the genome-wide level in this group.
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  • 文章类型: Dataset
    作为经济上重要的植物寄生线虫(PPN),菲利皮耶维对小麦造成巨大损害,现在它在许多国家被广泛记录。虽然已经发表了PPN的多个基因组,尚未对H.filipjevi进行高质量的基因组组装和注释。这项研究提出了H.filipjevi的染色体尺度基因组组装和注释,利用Illumina短读的组合,PacBio长读,和Hi-C测序技术。基因组由9个假染色体组成,包含134.19Mb的序列,支架N50长度为11.88Mb。总的来说,10036个基因被注释,占预测的总蛋白质编码基因的75.20%。我们的研究为H.filipjevi提供了第一个染色体尺度的基因组,这也是谷物囊肿线虫(CCN)的首个高质量基因组。它为谷物囊肿线虫病的进一步生物学研究和病虫害管理提供了宝贵的基因组资源。
    As an economically important plant parasitic nematode (PPN), Heterodera filipjevi causes great damage on wheat, and now it was widely recorded in many countries. While multiple genomes of PPNs have been published, high-quality genome assembly and annotation on H. filipjevi have yet to be performed. This study presents a chromosome-scale genome assembly and annotation for H. filipjevi, utilizing a combination of Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. The genome consists of 9 pseudo-chromosomes that contain 134.19 Mb of sequence, with a scaffold N50 length of 11.88 Mb. In total, 10,036 genes were annotated, representing 75.20% of the total predicted protein-coding genes. Our study provides the first chromosome-scale genome for H. filipjevi, which is also the inaugural high-quality genome of cereal cyst nematodes (CCNs). It provides a valuable genomic resource for further biological research and pest management of cereal cyst nematodes disease.
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  • 文章类型: Journal Article
    我们介绍了同种多倍体根结线虫Meloidogynejavanica的染色体规模基因组组装。我们表明,javanica基因组主要是异源四倍体,包括两个亚基因组,A和B,这很可能源于两个祖先亲本物种的杂交。使用全长非嵌合转录本注释组装,与参考数据库的比较,和从头算预测技术,并且使用祖先k-mer光谱分析对亚基因组进行了分期。亚基因组B似乎显示出染色体重叠群的裂变,虽然亚基因组之间存在大量的同质性,我们还确定了缺乏同系性的区域,这些区域可能在杂交之前或之后在祖先基因组中已经分化。这种带注释和分阶段的基因组组装形成了理解这些全球重要植物病原体的起源和遗传学的重要资源。
    We present the chromosome-scale genome assembly of the allopolyploid root-knot nematode Meloidogyne javanica. We show that the M. javanica genome is predominantly allotetraploid, comprising two subgenomes, A and B, that most likely originated from hybridisation of two ancestral parental species. The assembly was annotated using full-length non-chimeric transcripts, comparison to reference databases, and ab initio prediction techniques, and the subgenomes were phased using ancestral k-mer spectral analysis. Subgenome B appears to show fission of chromosomal contigs, and while there is substantial synteny between subgenomes, we also identified regions lacking synteny that may have diverged in the ancestral genomes prior to or following hybridisation. This annotated and phased genome assembly forms a significant resource for understanding the origins and genetics of these globally important plant pathogens.
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  • 文章类型: Journal Article
    Spirocercalupi是一种寄生线虫,主要影响家犬。它会导致螺旋体病,一种通常是致命的疾病。组装的S.lupi基因组草案由13,627个预测的蛋白质编码基因组成,长度约为150Mb。几种已知的驱虫基因靶标,例如β-微管蛋白,谷氨酸,通过将秀丽隐杆线虫驱虫基因靶标的直系同源物以及直系同源物与已知的疫苗候选物进行比较,在Lupi中鉴定了GABA受体以及已知的疫苗基因靶标,例如半胱氨酸蛋白酶抑制剂和细胞因子。通过包含-排除策略预测新的驱虫药靶标,并通过免疫信息学方法预测新的疫苗靶标。新的驱虫靶标包括DNA指导的RNA聚合酶,几丁质合成酶,聚合酶,和其他酶。新的疫苗靶标包括角质层胶原蛋白。这些基因靶标为新药鉴定和疫苗设计提供了启动平台。
    Spirocerca lupi is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of S. lupi consists of 13,627 predicted protein-coding genes and is approximately 150 Mb in length. Several known anthelmintic gene targets such as for β-Tubulin, glutamate, and GABA receptors as well as known vaccine gene targets such as cysteine protease inhibitor and cytokines were identified in S. lupi by comparing orthologs of C. elegans anthelmintic gene targets as well as orthologs to known vaccine candidates. New anthelmintic targets were predicted through an inclusion-exclusion strategy and new vaccine targets were predicted through an immunoinformatics approach. New anthelminthic targets include DNA-directed RNA polymerases, chitin synthase, polymerases, and other enzymes. New vaccine targets include cuticle collagens. These gene targets provide a starting platform for new drug identification and vaccine design.
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  • 文章类型: Journal Article
    核激素受体(NHR)是针对线虫感染和抗性的新兴目标候选物。然而,在寄生线虫中缺乏NHR编码基因的全面信息。在这项研究中,我们为人类和动物的60种主要寄生线虫策划了nhr基因家族。与自由生活模式生物秀丽隐杆线虫相比,在寄生物种中发现了nhr家族的显着收缩,随着线虫分化体I(10-13)的遗传多样化和保护,III(16-42),IV(33-35)和V(25-64)。使用体外生物系统,我们证明了采血线虫中的40个nhr基因对宿主血清和一个nhr基因(即,nhr-64)始终受到驱虫药的刺激(即,伊维菌素,噻菌灵和左旋咪唑);使用高通量RNA干扰平台,我们击倒了43个扭曲H.contortus的nhr基因,并鉴定了至少两个生存力所需的基因(即,nhr-105)和发展(即,nhr-17)体外该寄生线虫的感染性幼虫。利用H.contortus的nhr基因的初步功能图谱将启动该基因家族在线虫遗传学中的生物学研究,感染,和宿主动物体内的驱虫代谢,以及有希望发现新的干预目标。
    Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the nhr gene family for 60 major parasitic nematodes from humans and animals. Compared with the free-living model organism Caenorhabditis elegans, a remarkable contraction of the nhr family was revealed in parasitic species, with genetic diversification and conservation unveiled among nematode Clades I (10-13), III (16-42), IV (33-35) and V (25-64). Using an in vitro biosystem, we demonstrated that 40 nhr genes in a blood-feeding nematode Haemonchus contortus (clade V; barber\'s pole worm) were responsive to host serum and one nhr gene (i.e., nhr-64) was consistently stimulated by anthelmintics (i.e., ivermectin, thiabendazole and levamisole); Using a high-throughput RNA interference platform, we knocked down 43 nhr genes of H. contortus and identified at least two genes that are required for the viability (i.e., nhr-105) and development (i.e., nhr-17) of the infective larvae of this parasitic nematode in vitro. Harnessing this preliminary functional atlas of nhr genes for H. contortus will prime the biological studies of this gene family in nematode genetics, infection, and anthelmintic metabolism within host animals, as well as the promising discovery of novel intervention targets.
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  • 文章类型: Journal Article
    钩虫是寄生虫,与线虫模型密切相关的秀丽隐杆线虫,这是全世界的重大经济和健康负担。主要有三种钩虫(Necatoramericanus,十二指肠囊肿,Ancylostomaceylanicum)感染人类。来自19属的另外100种钩虫感染灵长类动物,反刍动物,和食肉动物。这些物种中只有7种存在遗传数据。基因组序列只能从两个属中的四个物种获得,剩下96个(特别是那些寄生野生动物)没有任何基因组数据。最近的钩虫基因组发表于5年前,黄昏离开田野.然而,从单个钩虫组装基因组可能会带来新的曙光。在这里,我们总结了进展,挑战,以及研究这些被忽视但重要的寄生线虫的机会。
    Hookworms are parasites, closely related to the model nematode Caenorhabditis elegans, that are a major economic and health burden worldwide. Primarily three hookworm species (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) infect humans. Another 100 hookworm species from 19 genera infect primates, ruminants, and carnivores. Genetic data exist for only seven of these species. Genome sequences are available from only four of these species in two genera, leaving 96 others (particularly those parasitizing wildlife) without any genomic data. The most recent hookworm genomes were published 5 years ago, leaving the field in a dusk. However, assembling genomes from single hookworms may bring a new dawn. Here we summarize advances, challenges, and opportunities for studying these neglected but important parasitic nematodes.
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