RESUMEN
Type 2 diabetes mellitus (T2D), a major cause of worldwide morbidity and mortality, is characterized by dysfunction of insulin-producing pancreatic islet ß cells1,2. T2D genome-wide association studies (GWAS) have identified hundreds of signals in non-coding and ß cell regulatory genomic regions, but deciphering their biological mechanisms remains challenging3-5. Here, to identify early disease-driving events, we performed traditional and multiplexed pancreatic tissue imaging, sorted-islet cell transcriptomics and islet functional analysis of early-stage T2D and control donors. By integrating diverse modalities, we show that early-stage T2D is characterized by ß cell-intrinsic defects that can be proportioned into gene regulatory modules with enrichment in signals of genetic risk. After identifying the ß cell hub gene and transcription factor RFX6 within one such module, we demonstrated multiple layers of genetic risk that converge on an RFX6-mediated network to reduce insulin secretion by ß cells. RFX6 perturbation in primary human islet cells alters ß cell chromatin architecture at regions enriched for T2D GWAS signals, and population-scale genetic analyses causally link genetically predicted reduced RFX6 expression with increased T2D risk. Understanding the molecular mechanisms of complex, systemic diseases necessitates integration of signals from multiple molecules, cells, organs and individuals, and thus we anticipate that this approach will be a useful template to identify and validate key regulatory networks and master hub genes for other diseases or traits using GWAS data.
Asunto(s)
Diabetes Mellitus Tipo 2 , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Islotes Pancreáticos , Humanos , Estudios de Casos y Controles , Separación Celular , Cromatina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Redes Reguladoras de Genes/genética , Estudio de Asociación del Genoma Completo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Reproducibilidad de los ResultadosRESUMEN
Multiplexed antibody-based imaging enables the detailed characterization of molecular and cellular organization in tissues. Advances in the field now allow high-parameter data collection (>60 targets); however, considerable expertise and capital are needed to construct the antibody panels employed by these methods. Organ mapping antibody panels are community-validated resources that save time and money, increase reproducibility, accelerate discovery and support the construction of a Human Reference Atlas.
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Anticuerpos , Recursos Comunitarios , Humanos , Reproducibilidad de los Resultados , Diagnóstico por ImagenRESUMEN
Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.
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Pandemias , Triticum , Triticum/genética , Fitomejoramiento , Enfermedades de las Plantas/microbiología , Genómica , HongosRESUMEN
Plant fungal parasites manipulate host metabolism to support their own survival. Among the many central metabolic pathways altered during infection, the glyoxylate cycle is frequently upregulated in both fungi and their host plants. Here, we examined the response of the glyoxylate cycle in bread wheat (Triticum aestivum) to infection by the obligate biotrophic fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Gene expression analysis revealed that wheat genes encoding the two unique enzymes of the glyoxylate cycle, isocitrate lyase (TaICL) and malate synthase, diverged in their expression between susceptible and resistant Pst interactions. Focusing on TaICL, we determined that the TaICL B homoeolog is specifically upregulated during early stages of a successful Pst infection. Furthermore, disruption of the B homoeolog alone was sufficient to significantly perturb Pst disease progression. Indeed, Pst infection of the TaICL-B disruption mutant (TaICL-BY400*) was inhibited early during initial penetration, with the TaICL-BY400* line also accumulating high levels of malic acid, citric acid, and aconitic acid. Exogenous application of malic acid or aconitic acid also suppressed Pst infection, with trans-aconitic acid treatment having the most pronounced effect by decreasing fungal biomass 15-fold. Thus, enhanced TaICL-B expression during Pst infection may lower accumulation of malic acid and aconitic acid to promote Pst proliferation. As exogenous application of aconitic acid and malic acid has previously been shown to inhibit other critical pests and pathogens, we propose TaICL as a potential target for disruption in resistance breeding that could have wide-reaching protective benefits for wheat and beyond.
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Glioxilatos , Isocitratoliasa , Malato Sintasa , Enfermedades de las Plantas , Puccinia , Triticum , Triticum/microbiología , Triticum/genética , Triticum/metabolismo , Triticum/enzimología , Isocitratoliasa/metabolismo , Isocitratoliasa/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Glioxilatos/metabolismo , Malato Sintasa/metabolismo , Malato Sintasa/genética , Puccinia/fisiología , Puccinia/patogenicidad , Regulación de la Expresión Génica de las Plantas , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Ten years ago, (black) stem rust - the most damaging of wheat (Triticum aestivum) rusts - re-emerged in western Europe. Disease incidences have since increased in scale and frequency. Here, we investigated the likely underlying causes and used those to propose urgently needed mitigating actions. We report that the first large-scale UK outbreak of the wheat stem rust fungus, Puccinia graminis f. sp. tritici (Pgt), in 2022 may have been caused by timely arrival of airborne urediniospores from southwest Europe. The drive towards later-maturing wheat varieties in the UK may be exacerbating Pgt incidences, which could have disastrous consequences. Indeed, infection assays showed that two UK Pgt isolates from 2022 could infect over 96% of current UK wheat varieties. We determined that the temperature response data in current disease risk simulation models are outdated. Analysis of germination rates for three current UK Pgt isolates showed substantial variation in temperature response functions, suggesting that the accuracy of disease risk simulations would be substantially enhanced by incorporating data from prevailing Pgt isolates. As Pgt incidences continue to accelerate in western Europe, we advocate for urgent action to curtail Pgt losses and help safeguard future wheat production across the region.
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Enfermedades de las Plantas , Tallos de la Planta , Triticum , Triticum/microbiología , Enfermedades de las Plantas/microbiología , Europa (Continente) , Tallos de la Planta/microbiología , Puccinia/patogenicidad , Puccinia/fisiología , Temperatura , Basidiomycota/fisiología , Basidiomycota/patogenicidad , Reino Unido/epidemiologíaRESUMEN
Plant pathogens suppress defense responses to evade recognition and promote successful colonization. Although identifying the genes essential for pathogen ingress has traditionally relied on screening mutant populations, the post-genomic era provides an opportunity to develop novel approaches that accelerate identification. Here, RNA-seq analysis of 68 pathogen-infected bread wheat (Triticum aestivum) varieties, including three (Oakley, Solstice and Santiago) with variable levels of susceptibility, uncovered a branched-chain amino acid aminotransferase (termed TaBCAT1) as a positive regulator of wheat rust susceptibility. We show that TaBCAT1 is required for yellow and stem rust infection and likely functions in branched-chain amino acid (BCAA) metabolism, as TaBCAT1 disruption mutants had elevated BCAA levels. TaBCAT1 mutants also exhibited increased levels of salicylic acid (SA) and enhanced expression of associated defense genes, indicating that BCAA regulation, via TaBCAT1, has a key role in SA-dependent defense activation. We also identified an association between the levels of BCAAs and resistance to yellow rust infection in wheat. These findings provide insight into SA-mediated defense responses in wheat and highlight the role of BCAA metabolism in the defense response. Furthermore, TaBCAT1 could be manipulated to potentially provide resistance to two of the most economically damaging diseases of wheat worldwide.
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Aminoácidos/metabolismo , Basidiomycota/fisiología , Resistencia a la Enfermedad , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Transaminasas/metabolismo , Triticum/enzimología , Análisis por Conglomerados , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Homeostasis , Mitocondrias/metabolismo , Modelos Biológicos , Mutación/genética , Proteínas de Plantas/genética , Ácido Salicílico/metabolismoRESUMEN
The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intraislet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion. To define morphological characteristics of capillaries and nerve fibers in islets and acinar tissue compartments, we analyzed neurovascular assembly across the largest cohort of T1D and normal individuals studied thus far. Because innervation has been studied extensively in rodent models of T1D, we also compared the neurovascular architecture between mouse and human pancreas and assembled transcriptomic profiles of molecules guiding islet angiogenesis and neuronal development. We found striking interspecies differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting that posttranscriptional regulation may be involved in this process. To determine whether islet neurovascular arrangement is altered after beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10-yr duration), and longstanding T1D (>10-yr duration) donors. Recent-onset T1D showed greater islet and acinar capillary density compared to non-diabetic and longstanding T1D donors. Both recent-onset and longstanding T1D had greater islet nerve fiber density compared to non-diabetic donors. We did not detect changes in sympathetic axons in either T1D cohort. Additionally, nerve fibers overlapped with extracellular matrix (ECM), supporting its role in the formation and function of axonal processes. These results indicate that pancreatic capillaries and nerve fibers persist in T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components.NEW & NOTEWORTHY Defining the neurovascular architecture in the pancreas of individuals with type 1 diabetes (T1D) is crucial to understanding the mechanisms of dysregulated glucagon secretion. In the largest T1D cohort of biobanked tissues analyzed to date, we found that pancreatic capillaries and nerve fibers persist in human T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components. Because innervation has been studied extensively in rodent T1D models, our studies also provide the first rigorous direct comparisons of neurovascular assembly in mouse and human, indicating dramatic interspecies differences.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Células Secretoras de Glucagón , Islotes Pancreáticos , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 1/metabolismo , Islotes Pancreáticos/metabolismo , Glucagón/metabolismo , Capilares/metabolismo , Células Secretoras de Glucagón/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fibras Nerviosas/metabolismoRESUMEN
Pathogen populations are expected to evolve virulence traits in response to resistance deployed in agricultural settings. However, few temporal datasets have been available to characterize this process at the population level. Here, we examined two temporally separated populations of Puccinia coronata f. sp. avenae (Pca), which causes crown rust disease in oat (Avena sativa) sampled from 1990 to 2015. We show that a substantial increase in virulence occurred from 1990 to 2015 and this was associated with a genetic differentiation between populations detected by genome-wide sequencing. We found strong evidence for genetic recombination in these populations, showing the importance of the alternate host in generating genotypic variation through sexual reproduction. However, asexual expansion of some clonal lineages was also observed within years. Genome-wide association analysis identified seven Avr loci associated with virulence towards fifteen Pc resistance genes in oat and suggests that some groups of Pc genes recognize the same pathogen effectors. The temporal shift in virulence patterns in the Pca populations between 1990 and 2015 is associated with changes in allele frequency in these genomic regions. Nucleotide diversity patterns at a single Avr locus corresponding to Pc38, Pc39, Pc55, Pc63, Pc70, and Pc71 showed evidence of a selective sweep associated with the shift to virulence towards these resistance genes in all 2015 collected isolates.
Asunto(s)
Frecuencia de los Genes , Genes Fúngicos , Puccinia/genética , Avena/microbiología , Polimorfismo Genético , Puccinia/patogenicidad , Selección Genética , Virulencia/genéticaRESUMEN
Functional characterization of effector proteins of fungal obligate biotrophic pathogens, especially confirmation of avirulence (Avr) properties, has been notoriously difficult, due to the experimental intractability of many of these organisms. Previous studies in wheat have shown promising data suggesting the type III secretion system (T3SS) of bacteria may be a suitable surrogate for delivery and detection of Avr properties of fungal effectors. However, these delivery systems were tested in the absence of confirmed Avr effectors. Here, we tested two previously described T3SS-mediated delivery systems for their suitability when delivering two confirmed Avr effectors from two fungal pathogens of wheat, Puccinia graminis f. sp. tritici and Magnaporthe oryzae pathotype tritici. We showed that both effectors (AvrSr50 and AvrRmg8) were unable to elicit a hypersensitive response on wheat seedlings with the corresponding resistance gene when expressed by the Pseudomonas fluorescens "Effector to Host Analyser" (EtHAn) system. Furthermore, we found the utility of Burkholderia glumae for screening Avr phenotypes is severely limited, as the wild-type strain elicits nonhost cell death in multiple wheat accessions. These results provide valuable insight into the suitability of these systems for screening fungal effectors for Avr properties that may help guide further development of surrogate bacterial delivery systems in wheat. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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Bacterias , Triticum , Triticum/microbiología , Enfermedades de las Plantas/microbiologíaRESUMEN
BACKGROUND: Transcriptomics is being increasingly applied to generate new insight into the interactions between plants and their pathogens. For the wheat yellow (stripe) rust pathogen (Puccinia striiformis f. sp. tritici, Pst) RNA-based sequencing (RNA-Seq) has proved particularly valuable, overcoming the barriers associated with its obligate biotrophic nature. This includes the application of RNA-Seq approaches to study Pst and wheat gene expression dynamics over time and the Pst population composition through the use of a novel RNA-Seq based surveillance approach called "field pathogenomics". As a dual RNA-Seq approach, the field pathogenomics technique also provides gene expression data from the host, giving new insight into host responses. However, this has created a wealth of data for interrogation. RESULTS: Here, we used the field pathogenomics approach to generate 538 new RNA-Seq datasets from Pst-infected field wheat samples, doubling the amount of transcriptomics data available for this important pathosystem. We then analysed these datasets alongside 66 RNA-Seq datasets from four Pst infection time-courses and 420 Pst-infected plant field and laboratory samples that were publicly available. A database of gene expression values for Pst and wheat was generated for each of these 1024 RNA-Seq datasets and incorporated into the development of the rust expression browser ( http://www.rust-expression.com ). This enables for the first time simultaneous 'point-and-click' access to gene expression profiles for Pst and its wheat host and represents the largest database of processed RNA-Seq datasets available for any of the three Puccinia wheat rust pathogens. We also demonstrated the utility of the browser through investigation of expression of putative Pst virulence genes over time and examined the host plants response to Pst infection. CONCLUSIONS: The rust expression browser offers immense value to the wider community, facilitating data sharing and transparency and the underlying database can be continually expanded as more datasets become publicly available.
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Basidiomycota , Transcriptoma , Basidiomycota/genética , Enfermedades de las Plantas/genética , Triticum/genética , VirulenciaRESUMEN
The plant apoplast is a harsh environment in which hydrolytic enzymes, especially proteases, accumulate during pathogen infection. However, the defense functions of most apoplastic proteases remain largely elusive. We show here that a newly identified small cysteine-rich secreted protein PC2 from the potato late blight pathogen Phytophthora infestans induces immunity in Solanum plants only after cleavage by plant apoplastic subtilisin-like proteases, such as tomato P69B. A minimal 61 amino acid core peptide carrying two key cysteines, conserved widely in most oomycete species, is sufficient for PC2-induced cell death. Furthermore, we showed that Kazal-like protease inhibitors, such as EPI1, produced by P. infestans prevent PC2 cleavage and dampen PC2 elicited host immunity. This study reveals that cleavage of pathogen proteins to release immunogenic peptides is an important function of plant apoplastic proteases.
Asunto(s)
Phytophthora infestans , Solanum lycopersicum , Solanum tuberosum , Solanum , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , SubtilisinasRESUMEN
Puccinia kuehnii is an obligate biotrophic fungal pathogen that causes orange rust of sugarcane, which is prevalent in many countries around the globe. In the United States, orange rust was first detected in sugarcane in Florida in 2007 and poses a persistent and economically damaging threat to the sugarcane industry in this region. Here, we generated the first genome assemblies for two isolates of P. kuehnii (1040 and 2143) collected in Florida in 2017 from two sugarcane cultivars, CL85-1040 and CP89-2143, respectively. These two rust genome resources will be of immense value for future genomic studies, particularly further exploration of the predicted secretomes that may help define key pathogenicity determinants for this economically important pathogen.
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Saccharum , Genómica , Enfermedades de las Plantas , Puccinia , SecretomaRESUMEN
AIMS/HYPOTHESIS: Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood. METHODS: To characterise the pancreatic endocrine and exocrine compartments in diabetes, we studied pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes. Islet cell mass, islet morphometry, exocrine mass, acinar cell size and number and pancreas fibrosis were assessed by immunohistochemical staining. To better understand possible mechanisms of altered pancreas size, we measured pancreas size in three mouse models of insulin deficiency. RESULTS: Pancreases from donors with type 1 diabetes were approximately 45% smaller than those from donors without diabetes (47.4 ± 2.6 vs 85.7 ± 3.7 g), independent of diabetes duration or age of onset. Diabetic donor pancreases had decreased beta cell mass (0.061 ± 0.025 vs 0.94 ± 0.21 g) and reduced total exocrine mass (42.0 ± 4.9 vs 96.1 ± 6.5 g). Diabetic acinar cells were similar in size but fewer in number compared with those in pancreases from non-diabetic donors (63.7 ± 8.1 × 109 vs 121.6 ± 12.2 × 109 cells/pancreas), likely accounting for the difference in pancreas size. Within the type 1 diabetes exocrine tissue, there was a greater degree of fibrosis. The pancreases in three mouse models of insulin deficiency were similar in size to those in control mice. CONCLUSIONS/INTERPRETATION: Pancreases from donors with type 1 diabetes are smaller than normal donor pancreases because exocrine cells are fewer in number rather than smaller in size; these changes occur early in the disease process. Our mouse data suggest that decreased pancreas size in type 1 diabetes is not directly caused by insulin deficiency, but the precise mechanism responsible remains unclear.
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Diabetes Mellitus Tipo 1/metabolismo , Páncreas Exocrino/metabolismo , Células Acinares/metabolismo , Animales , Femenino , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Ratones , Páncreas/metabolismoRESUMEN
In recent years, the number of emergent plant pathogens (EPPs) has grown substantially, threatening agroecosystem stability and native biodiversity. Contributing factors include, among others, shifts in biogeography, with EPP spread facilitated by the global unification of monocultures in modern agriculture, high volumes of trade in plants and plant products and an increase in sexual recombination within pathogen populations. The unpredictable nature of EPPs as they move into new territories is a situation that has led to sudden and widespread epidemics. Understanding the underlying causes of pathogen emergence is key to managing the impact of EPPs. Here, we review some factors specifically influencing the emergence of oomycete and fungal EPPs, including new introductions through anthropogenic movement, natural dispersal and weather events, as well as genetic factors linked to shifts in host range.
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Biodiversidad , Hongos/fisiología , Especificidad del Huésped , Oomicetos/fisiología , Enfermedades de las Plantas/microbiología , Plantas/microbiología , AgriculturaRESUMEN
BACKGROUND: Effective disease management depends on timely and accurate diagnosis to guide control measures. The capacity to distinguish between individuals in a pathogen population with specific properties such as fungicide resistance, toxin production and virulence profiles is often essential to inform disease management approaches. The genomics revolution has led to technologies that can rapidly produce high-resolution genotypic information to define individual variants of a pathogen species. However, their application to complex fungal pathogens has remained limited due to the frequent inability to culture these pathogens in the absence of their host and their large genome sizes. RESULTS: Here, we describe the development of Mobile And Real-time PLant disEase (MARPLE) diagnostics, a portable, genomics-based, point-of-care approach specifically tailored to identify individual strains of complex fungal plant pathogens. We used targeted sequencing to overcome limitations associated with the size of fungal genomes and their often obligately biotrophic nature. Focusing on the wheat yellow rust pathogen, Puccinia striiformis f.sp. tritici (Pst), we demonstrate that our approach can be used to rapidly define individual strains, assign strains to distinct genetic lineages that have been shown to correlate tightly with their virulence profiles and monitor genes of importance. CONCLUSIONS: MARPLE diagnostics enables rapid identification of individual pathogen strains and has the potential to monitor those with specific properties such as fungicide resistance directly from field-collected infected plant tissue in situ. Generating results within 48 h of field sampling, this new strategy has far-reaching implications for tracking plant health threats.
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Basidiomycota/aislamiento & purificación , Pruebas Diagnósticas de Rutina/métodos , Enfermedades de las Plantas/microbiología , Sistemas de Atención de Punto , Basidiomycota/clasificación , Enfermedades de las Plantas/clasificaciónRESUMEN
Physiological races of the oomycete Albugo candida are biotrophic pathogens of diverse plant species, primarily the Brassicaceae, and cause infections that suppress host immunity to other pathogens. However, A. candida race diversity and the consequences of host immunosuppression are poorly understood in the field. We report a method that enables sequencing of DNA of plant pathogens and plant-associated microbes directly from field samples (Pathogen Enrichment Sequencing: PenSeq). We apply this method to explore race diversity in A. candida and to detect A. candida-associated microbes in the field (91 A. candida-infected plants). We show with unprecedented resolution that each host plant species supports colonization by one of 17 distinct phylogenetic lineages, each with an unique repertoire of effector candidate alleles. These data reveal the crucial role of sexual and asexual reproduction, polyploidy and host domestication in A. candida specialization on distinct plant species. Our bait design also enabled phylogenetic assignment of DNA sequences from bacteria and fungi from plants in the field. This paper shows that targeted sequencing has a great potential for the study of pathogen populations while they are colonizing their hosts. This method could be applied to other microbes, especially to those that cannot be cultured.
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Brassicaceae/genética , Brassicaceae/microbiología , Variación Genética , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Ploidias , Secuencia de Bases , Brassicaceae/crecimiento & desarrollo , Frecuencia de los Genes/genética , Sitios Genéticos , Genética de Población , Genotipo , Heterocigoto , Filogenia , Hojas de la Planta/genética , Hojas de la Planta/microbiología , Recombinación Genética/genéticaRESUMEN
Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels.
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Carcinogénesis/genética , Proteínas de Unión al ADN/genética , Neoplasias Gastrointestinales/genética , Selenoproteínas/genética , Proteína p53 Supresora de Tumor/genética , Animales , Daño del ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Neoplasias Gastrointestinales/patología , Regulación Neoplásica de la Expresión Génica , Homeostasis , Humanos , Masculino , Oxidación-Reducción , Estrés Oxidativo/genética , Selenio/metabolismo , Selenoproteínas/metabolismo , Transcriptoma/genética , Pez Cebra/genéticaRESUMEN
Reader Comments | Submit a Comment The white paper reports the deliberations of a workshop focused on biotic challenges to plant health held in Washington, D.C. in September 2016. Ensuring health of food plants is critical to maintaining the quality and productivity of crops and for sustenance of the rapidly growing human population. There is a close linkage between food security and societal stability; however, global food security is threatened by the vulnerability of our agricultural systems to numerous pests, pathogens, weeds, and environmental stresses. These threats are aggravated by climate change, the globalization of agriculture, and an over-reliance on nonsustainable inputs. New analytical and computational technologies are providing unprecedented resolution at a variety of molecular, cellular, organismal, and population scales for crop plants as well as pathogens, pests, beneficial microbes, and weeds. It is now possible to both characterize useful or deleterious variation as well as precisely manipulate it. Data-driven, informed decisions based on knowledge of the variation of biotic challenges and of natural and synthetic variation in crop plants will enable deployment of durable interventions throughout the world. These should be integral, dynamic components of agricultural strategies for sustainable agriculture.
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Agricultura/métodos , Productos Agrícolas/crecimiento & desarrollo , Abastecimiento de Alimentos , Investigación Biomédica Traslacional/métodos , Biotecnología/métodos , Cambio Climático , Productos Agrícolas/microbiología , Productos Agrícolas/parasitología , Humanos , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/parasitologíaRESUMEN
Parasite effector proteins target various host cell compartments to alter host processes and promote infection. How effectors cross membrane-rich interfaces to reach these compartments is a major question in effector biology. Growing evidence suggests that effectors use molecular mimicry to subvert host cell machinery for protein sorting. We recently identified chloroplast-targeted protein 1 (CTP1), a candidate effector from the poplar leaf rust fungus Melampsora larici-populina that carries a predicted transit peptide and accumulates in chloroplasts and mitochondria. Here, we show that the CTP1 transit peptide is necessary and sufficient for accumulation in the stroma of chloroplasts. CTP1 is part of a Melampsora-specific family of polymorphic secreted proteins. Two members of that family, CTP2 and CTP3, also translocate in chloroplasts in an N-terminal signal-dependent manner. CTP1, CTP2 and CTP3 are cleaved when they accumulate in chloroplasts, while they remain intact when they do not translocate into chloroplasts. Our findings reveal that fungi have evolved effector proteins that mimic plant-specific sorting signals to traffic within plant cells.
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Cloroplastos/metabolismo , Proteínas Fúngicas/metabolismo , Factores de Virulencia/metabolismo , Basidiomycota/fisiología , Imitación Molecular , Enfermedades de las Plantas/microbiología , Populus/microbiología , Transporte de ProteínasRESUMEN
Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. Although this concept has become textbook knowledge, it is only based on studying a few loci, including 45S rDNA. To provide a more comprehensive insight into the genetic makeup of arbuscular endomycorrhizal fungi, we applied de novo genome sequencing of individual nuclei of Rhizophagus irregularis. This revealed a surprisingly low level of polymorphism between nuclei. In contrast, within a nucleus, the 45S rDNA repeat unit turned out to be highly diverged. This finding demystifies a long-lasting hypothesis on the complex genetic makeup of arbuscular endomycorrhizal fungi. Subsequent genome assembly resulted in the first draft reference genome sequence of an arbuscular endomycorrhizal fungus. Its length is 141 Mbps, representing over 27,000 protein-coding gene models. We used the genomic sequence to reinvestigate the phylogenetic relationships of Rhizophagus irregularis with other fungal phyla. This unambiguously demonstrated that Glomeromycota are more closely related to Mucoromycotina than to its postulated sister Dikarya.