RESUMEN
This corrects the article DOI: 10.1038/nature21370.
RESUMEN
Chenopodium quinoa (quinoa) is a highly nutritious grain identified as an important crop to improve world food security. Unfortunately, few resources are available to facilitate its genetic improvement. Here we report the assembly of a high-quality, chromosome-scale reference genome sequence for quinoa, which was produced using single-molecule real-time sequencing in combination with optical, chromosome-contact and genetic maps. We also report the sequencing of two diploids from the ancestral gene pools of quinoa, which enables the identification of sub-genomes in quinoa, and reduced-coverage genome sequences for 22 other samples of the allotetraploid goosefoot complex. The genome sequence facilitated the identification of the transcription factor likely to control the production of anti-nutritional triterpenoid saponins found in quinoa seeds, including a mutation that appears to cause alternative splicing and a premature stop codon in sweet quinoa strains. These genomic resources are an important first step towards the genetic improvement of quinoa.
Asunto(s)
Chenopodium quinoa/genética , Genoma de Planta/genética , Empalme Alternativo/genética , Diploidia , Evolución Molecular , Pool de Genes , Anotación de Secuencia Molecular , Mutación , Poliploidía , Saponinas/biosíntesis , Análisis de Secuencia de ADN , Factores de Transcripción/metabolismoRESUMEN
The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
Asunto(s)
Proteínas Portadoras/genética , Eritrocitos/parasitología , Plasmodium knowlesi/genética , Plasmodium knowlesi/patogenicidad , Proteínas Protozoarias/genética , Animales , Células Cultivadas , Humanos , Macaca fascicularis , Macaca mulatta , Malaria , Polimorfismo de Nucleótido Simple , ZoonosisRESUMEN
Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.
Asunto(s)
Aedes/genética , Brugia Malayi , Exoma , Sitios Genéticos , Transcriptoma , Aedes/inmunología , Animales , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.
Asunto(s)
Adaptación Biológica/fisiología , Técnicas de Cultivo/métodos , Eritrocitos/parasitología , Plasmodium knowlesi/crecimiento & desarrollo , Plasmodium knowlesi/genética , Adaptación Biológica/genética , Animales , Secuencia de Bases , Clonación Molecular , Criopreservación , Cartilla de ADN/genética , Genotipo , Humanos , Macaca fascicularis , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
BACKGROUND: Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31(+) and CD31â» naive T cells to immune reconstitution and viral persistence is unknown. METHODS: In a cross-sectional (n = 94) and longitudinal (n = 10) study of human immunodeficiency virus (HIV)-infected patients before and after ART, we examined the ratio of CD31(+) to CD31â» naive CD4(+) T cells. In the longitudinal cohort we then quantified the concentration of HIV-1 DNA in each cell subset and performed single-genome amplification of virus from memory and naive T cells. RESULTS: Patients receiving ART had a higher proportion of CD31(+) CD4(+) T cells than HIV-1-infected individuals naive to ART and uninfected control subjects (P < .001 and .007, respectively). After 24 months of ART, the proportion of CD31(+) naive CD4(+) T cells did not change, the concentration of HIV-1 DNA in memory CD4(+) T cells significantly decreased over time (P < .001), and there was no change in the concentration of HIV-1 DNA in CD31(+) or CD31â» naive CD4(+) T cells (P = .751 and .251, respectively). Single-genome amplification showed no evidence of virus compartmentalization in memory and naive T cell subsets before or after ART. CONCLUSIONS: After ART, both CD31(+) and CD31â» naive CD4(+) T cells expand, and both subsets represent a stable, persistent reservoir of HIV-1.
Asunto(s)
Antirretrovirales/farmacología , Linfocitos T CD4-Positivos/efectos de los fármacos , Infecciones por VIH/sangre , VIH-1/efectos de los fármacos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios Transversales , Femenino , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Estudios Longitudinales , Masculino , Reacción en Cadena de la Polimerasa , Análisis de Regresión , Singapur , VictoriaRESUMEN
BACKGROUND: Post-translational modifications have a substantial influence on the structure and functions of protein. Post-translational phosphorylation is one of the most common modification that occur in intracellular proteins. Accurate prediction of protein phosphorylation sites is of great importance for the understanding of diverse cellular signalling processes in both the human body and in animals. In this study, we propose a new machine learning based protein phosphorylation site predictor, SiteSeek. SiteSeek is trained using a novel compact evolutionary and hydrophobicity profile to detect possible protein phosphorylation sites for a target sequence. The newly proposed method proves to be more accurate and exhibits a much stable predictive performance than currently existing phosphorylation site predictors. RESULTS: The performance of the proposed model was compared to nine existing different machine learning models and four widely known phosphorylation site predictors with the newly proposed PS-Benchmark_1 dataset to contrast their accuracy, sensitivity, specificity and correlation coefficient. SiteSeek showed better predictive performance with 86.6% accuracy, 83.8% sensitivity, 92.5% specificity and 0.77 correlation-coefficient on the four main kinase families (CDK, CK2, PKA, and PKC). CONCLUSION: Our newly proposed methods used in SiteSeek were shown to be useful for the identification of protein phosphorylation sites as it performed much better than widely known predictors on the newly built PS-Benchmark_1 dataset.
Asunto(s)
Algoritmos , Proteínas/química , Proteínas/metabolismo , Procesamiento Postranscripcional del ARN/fisiología , Análisis de Secuencia de Proteína/métodos , Secuencia de Aminoácidos , Sitios de Unión , Datos de Secuencia Molecular , Fosforilación , Unión ProteicaRESUMEN
BACKGROUND: N-linked glycosylation is a major mechanism for minimizing virus neutralizing antibody response and is present on the Human Immunodeficiency Virus (HIV) envelope glycoprotein. Although it is known that glycosylation changes can dramatically influence virus recognition by the host antibody, the actual contribution of compartmental differences in N-linked glycosylation patterns remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: We amplified the env gp120 C2-V5 region and analyzed 305 clones derived from plasma and other compartments from 15 HIV-1 patients. Bioinformatics and Bayesian network analyses were used to examine N-linked glycosylation differences between compartments. We found evidence for cellspecific single amino acid changes particular to monocytes, and significant variation was found in the total number of N-linked glycosylation sites between patients. Further, significant differences in the number of glycosylation sites were observed between plasma and cellular compartments. Bayesian network analyses showed an interdependency between N-linked glycosylation sites found in our study, which may have immense functional relevance. CONCLUSION: Our analyses have identified single cell/compartment-specific amino acid changes and differences in N-linked glycosylation patterns between plasma and diverse blood leukocytes. Bayesian network analyses showed associations inferring alternative glycosylation pathways. We believe that these studies will provide crucial insights into the host immune response and its ability in controlling HIV replication in vivo. These findings could also have relevance in shielding and evasion of HIV-1 from neutralizing antibodies.
Asunto(s)
Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/metabolismo , Infecciones por VIH/virología , VIH-1/metabolismo , Leucocitos/virología , Plasma/virología , Aminoácidos/genética , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Teorema de Bayes , Variación Genética , Glicosilación , Infecciones por VIH/tratamiento farmacológico , Humanos , Monocitos/virología , FilogeniaRESUMEN
Solanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome assembly and annotation of S. pimpinellifolium 'LA0480.' Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit- and yield-related traits in S. pimpinellifolium compared with cultivated tomato. The 'LA0480' genome assembly size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the 'LA0480' protein-coding genes. Additionally, we used DEAP to compare protein function between S. pimpinellifolium and cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. To understand the genomic basis for these differences in S. pimpinellifolium and S. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show that S. pimpinellifolium has a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in 'LA0480.' Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential of S. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness.
RESUMEN
High-throughput phenotyping produces multiple measurements over time, which require new methods of analyses that are flexible in their quantification of plant growth and transpiration, yet are computationally economic. Here we develop such analyses and apply this to a rice population genotyped with a 700k SNP high-density array. Two rice diversity panels, indica and aus, containing a total of 553 genotypes, are phenotyped in waterlogged conditions. Using cubic smoothing splines to estimate plant growth and transpiration, we identify four time intervals that characterize the early responses of rice to salinity. Relative growth rate, transpiration rate and transpiration use efficiency (TUE) are analysed using a new association model that takes into account the interaction between treatment (control and salt) and genetic marker. This model allows the identification of previously undetected loci affecting TUE on chromosome 11, providing insights into the early responses of rice to salinity, in particular into the effects of salinity on plant growth and transpiration.
Asunto(s)
Oryza/genética , Salinidad , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Ensayos Analíticos de Alto Rendimiento , Oryza/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transpiración de PlantasRESUMEN
Even though the treatment of human immunodeficiency virus (HIV)-infected individuals with highly active antiretroviral therapy (HAART) provides a complete control of plasma viremia to below detectable levels (<40 copies/mL plasma), there is an unequal distribution of all antiretroviral drugs across diverse cellular and anatomic compartments in vivo. The main consequence of this is the acquisition of resistance by HIV to all known classes of currently prescribed antiretroviral drugs and the establishment of HIV reservoirs in vivo. HIV has a distinct advantage of surviving in the host via both pre-and postintegration latency. The postintegration latency is caused by inert and metabolically inactive provirus, which cannot be accessed either by the immune system or the therapeutics. This integrated provirus provides HIV with a safe haven in the host where it is incessantly challenged by its immune selection pressure and also by HAART. Thus, the provirus is one of the strategies for viral concealment in the host and the provirus can be rekindled, through unknown stimuli, to create progeny for productive infection of the host. Thus, the reservoir establishment remains the biggest impediment to HIV eradication from the host. This review provides an overview of HIV reservoir sites and discusses both the virtues and problems associated with therapies/strategies targeting these reservoir sites in vivo.