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1.
Viruses ; 13(1)2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33477360

RESUMEN

The APOBEC3 family of proteins in mammals consists of cellular cytosine deaminases and well-known restriction factors against retroviruses, including lentiviruses. APOBEC3 genes are highly amplified and diversified in mammals, suggesting that their evolution and diversification have been driven by conflicts with ancient viruses. At present, lentiviruses, including HIV, the causative agent of AIDS, are known to encode a viral protein called Vif to overcome the antiviral effects of the APOBEC3 proteins of their hosts. Recent studies have revealed that the acquisition of an anti-APOBEC3 ability by lentiviruses is a key step in achieving successful cross-species transmission. Here, we summarize the current knowledge of the interplay between mammalian APOBEC3 proteins and viral infections and introduce a scenario of the coevolution of mammalian APOBEC3 genes and viruses.


Asunto(s)
Desaminasas APOBEC/metabolismo , Interacciones Huésped-Patógeno , Infecciones por Retroviridae/metabolismo , Infecciones por Retroviridae/virología , Retroviridae/fisiología , Desaminasas APOBEC/genética , Animales , Resistencia a la Enfermedad/genética , Evolución Molecular , Variación Genética , Genoma Viral , Interacciones Huésped-Patógeno/genética , Humanos , Lentivirus/fisiología , Filogenia , Infecciones por Retroviridae/transmisión , Especificidad de la Especie , Productos del Gen vif del Virus de la Inmunodeficiencia Humana
2.
Viruses ; 13(1)2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33478128

RESUMEN

Plant viruses cause devastating diseases in many agriculture systems, being a serious threat for the provision of adequate nourishment to a continuous growing population. At the present, there are no chemical products that directly target the viruses, and their control rely mainly on preventive sanitary measures to reduce viral infections that, although important, have proved to be far from enough. The current most effective and sustainable solution is the use of virus-resistant varieties, but which require too much work and time to obtain. In the recent years, the versatile gene editing technology known as CRISPR/Cas has simplified the engineering of crops and has successfully been used for the development of viral resistant plants. CRISPR stands for 'clustered regularly interspaced short palindromic repeats' and CRISPR-associated (Cas) proteins, and is based on a natural adaptive immune system that most archaeal and some bacterial species present to defend themselves against invading bacteriophages. Plant viral resistance using CRISPR/Cas technology can been achieved either through manipulation of plant genome (plant-mediated resistance), by mutating host factors required for viral infection; or through manipulation of virus genome (virus-mediated resistance), for which CRISPR/Cas systems must specifically target and cleave viral DNA or RNA. Viruses present an efficient machinery and comprehensive genome structure and, in a different, beneficial perspective, they have been used as biotechnological tools in several areas such as medicine, materials industry, and agriculture with several purposes. Due to all this potential, it is not surprising that viruses have also been used as vectors for CRISPR technology; namely, to deliver CRISPR components into plants, a crucial step for the success of CRISPR technology. Here we discuss the basic principles of CRISPR/Cas technology, with a special focus on the advances of CRISPR/Cas to engineer plant resistance against DNA and RNA viruses. We also describe several strategies for the delivery of these systems into plant cells, focusing on the advantages and disadvantages of the use of plant viruses as vectors. We conclude by discussing some of the constrains faced by the application of CRISPR/Cas technology in agriculture and future prospects.


Asunto(s)
Ingeniería Genética , Enfermedades de las Plantas/virología , Virus de Plantas/fisiología , Agricultura/métodos , Sistemas CRISPR-Cas , Productos Agrícolas/virología , Resistencia a la Enfermedad/genética , Edición Génica , Expresión Génica , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Genoma Viral , Interacciones Huésped-Patógeno/genética , Enfermedades de las Plantas/genética
3.
Med Sci Monit Basic Res ; 27: e929207, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33397841

RESUMEN

As of November 25, 2020, over 60 million people have been infected worldwide by COVID-19, causing almost 1.43 million deaths. Puzzling low incidence numbers and milder, non-fatal disease have been observed in Thailand and its Southeast (SE) Asian neighbors. Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait). In this study, we have plotted COVID-19 infection and death rates in SE Asian (SEA) countries against heterozygote HbE and thalassemia carrier prevalence. COVID-19 infection and death incidence numbers appear inversely correlated with the prevalence of HbE and thalassemia heterozygote populations. We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be positively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.


Asunto(s)
/genética , Resistencia a la Enfermedad/genética , Susceptibilidad a Enfermedades , Hemoglobina E/genética , Antivirales/uso terapéutico , Grupo de Ascendencia Continental Asiática , /inmunología , Dengue/genética , Heterocigoto , Humanos , Sistema Inmunológico , Interferones , Malaria/genética , Pandemias , Prevalencia , Tailandia/epidemiología , Talasemia/epidemiología , Talasemia/genética
4.
Nat Commun ; 12(1): 433, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33469010

RESUMEN

The poverty of disease resistance gene reservoirs limits the breeding of crops for durable resistance against evolutionary dynamic pathogens. Zymoseptoria tritici which causes Septoria tritici blotch (STB), represents one of the most genetically diverse and devastating wheat pathogens worldwide. No fully virulent Z. tritici isolates against synthetic wheats carrying the major resistant gene Stb16q have been identified. Here, we use comparative genomics, mutagenesis and complementation to identify Stb16q, which confers broad-spectrum resistance against Z. tritici. The Stb16q gene encodes a plasma membrane cysteine-rich receptor-like kinase that was recently introduced into cultivated wheat and which considerably slows penetration and intercellular growth of the pathogen.


Asunto(s)
Productos Agrícolas/genética , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Proteínas Serina-Treonina Quinasas/genética , Triticum/genética , Alelos , Ascomicetos/patogenicidad , Membrana Celular/enzimología , Productos Agrícolas/microbiología , Genes de Plantas/genética , Fitomejoramiento/métodos , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/microbiología , Semillas/genética , Triticum/enzimología , Triticum/microbiología
5.
Gene ; 773: 145415, 2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33444678

RESUMEN

Heat shock protein 27 (HSP27) plays an important role in protecting cells from various stress factors. This study aimed to investigate the function of HSP27 gene and its regulatory mechanism as infected by Escherichia coli (E. coli) at the tissue and cellular levels. Real-time PCR was used to detect the differential expression of HSP27 gene in F18 resistant and sensitive Sutai pigs and the differential expression upon E. coli F18ab, F18ac, K88ac bacterial supernatant, thallus infection and LPS induction in IPEC-J2. In addition, the HSP27 gene overexpression vector was constructed to detect the effect of the HSP27 gene overexpression on the adhesion of E. coli F18 to IPEC-J2, secretion of pro-inflammatory factors, and the expression of the upstream key genes in Mitogen-activated protein kinase (MAPK) pathway. Ribosomal S6 kinase (RSK2) is an important protein in the MAPK pathway. Therefore, the RSK2 gene overexpression vector was constructed and the number of colonies was counted after co-transfection of HSP27 and RSK2 gene. Results revealed that the expression level of HSP27 gene in resistant individuals in 11 tissues was higher than sensitive type. At the cellular level, the relative expression levels of HSP27 gene were increased after F18ab, F18ac bacterial supernatant, F18ab thallus infection, and LPS induction for 4 h (P < 0.01). The adhesion ability of E. coli F18ab to IPEC-J2 was significantly reduced after HSP27 gene overexpression (P < 0.01), and the concentration of pro-inflammatory factors in the HSP27 gene overexpression group was significantly reduced compared with the control group after F18ab infection (P < 0.05). Furthermore, the expression of RSK2 was significantly increased in HSP27 overexpression group upon F18ab infection (P < 0.01). The colonies quantitative results also showed that the number of colonies was significantly reduced after co-transfection of HSP27 and RSK2 gene. We indicated that the high expression of HSP27 gene may resist the inflammatory response caused by exogenous stress and enhance the ability of IPEC-J2 to resist E. coli F18 infection. RSK2 gene in the MAPK pathway may cooperate with HSP27 gene to participate in the immune response of the organism, which provides a theoretical basis for the study of the mechanism of anti-E. coli infection in piglets.


Asunto(s)
Resistencia a la Enfermedad/genética , Infecciones por Escherichia coli/genética , Escherichia coli/genética , Proteínas de Choque Térmico HSP27/genética , Animales , Adhesión Bacteriana/genética , Diarrea/genética , Diarrea/microbiología , Diarrea/veterinaria , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Proteínas de Escherichia coli/genética , Regulación de la Expresión Génica/genética , Porcinos/genética , Porcinos/microbiología , Enfermedades de los Porcinos/genética , Enfermedades de los Porcinos/microbiología
6.
Nat Commun ; 12(1): 707, 2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33514727

RESUMEN

Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.


Asunto(s)
Complejo I de Transporte de Electrón/ultraestructura , Mitocondrias/patología , Daño por Reperfusión Miocárdica/patología , NADH Deshidrogenasa/genética , Especies Reactivas de Oxígeno/metabolismo , Sustitución de Aminoácidos , Animales , Microscopía por Crioelectrón , ADN Mitocondrial/genética , Modelos Animales de Enfermedad , Resistencia a la Enfermedad/genética , Transporte de Electrón/genética , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Humanos , Preparación de Corazón Aislado , Leucina/genética , Masculino , Ratones , Ratones Transgénicos , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Membranas Mitocondriales/patología , Daño por Reperfusión Miocárdica/genética , NAD/metabolismo , NADH Deshidrogenasa/metabolismo , NADH Deshidrogenasa/ultraestructura , Oxidación-Reducción , Mutación Puntual , Prolina/genética
7.
Gene ; 770: 145345, 2021 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-33333217

RESUMEN

Selective breeding of genetically resistant animals is considered a promising strategy to face the problem of nematode resistance to anthelmintics and mitigate concerns about the presence of chemical residues in animal food products and the environment. Gastrointestinal nematode resistance is a complex, multifactorial trait related to host immunity. However, the mechanisms underlying host resistance and response to infection remain to be fully elucidated. In this context, the objective of this study was to provide insight into the chromosomal regions determining nematode resistance and resilience in Corriedale and resistance in Pampinta sheep breeds. A total of 170 single nucleotide polymorphisms (SNP) from 76 candidate genes for immune response were studied in 624 Corriedale and 304 Pampinta animals. Lambs underwent artificial or natural challenges with infective larvae mainly from Haemonchus contortus. Fecal egg counts, estimated breeding values for fecal egg counts, and rate of packed cell volume change and FAMACHA© score change over the challenge were used, when available, as indicators of host parasite resistance or resilience. Phenotype-genotype association studies were conducted and significance values obtained were adjusted for multiple testing errors. Eight SNPs, located on OARs 3, 6, 12, and 20, reached significance in Corriedale sheep under artificial challenge. Those SNP represent allelic variants from the MHC-Ovine Lymphocyte Antigen-DRA, two C-type lectin domain families, the Interleukin 2 receptor ß, the Toll-like receptor 10, the Mannan binding lectin serine peptidase 2, and the NLR family, CARD domain containing 4 genes. On Pampinta lambs under natural challenge, we found three significant SNPs, located in the TIMP metallopeptidase inhibitor 3, the FBJ murine osteosarcoma viral oncogene homolog, and the Interleukin 20 receptor alpha genes, on OARs 3, 7, and 8, respectively. The results obtained herein confirm genomic regions previously reported as associated with nematode resistance in other sheep breeds, reinforcing their role in host response to parasites. These findings contribute to gain knowledge on parasite resistance and resilience in Corriedale sheep and report for the first time SNPs associated with resistance to gastrointestinal parasite infections in Pampinta breed.


Asunto(s)
Resistencia a la Enfermedad/genética , Hemoncosis/genética , Haemonchus , Helmintiasis Animal/genética , Polimorfismo de Nucleótido Simple , Enfermedades de las Ovejas/genética , Ovinos/genética , Animales , Argentina , Ovinos/parasitología , Enfermedades de las Ovejas/parasitología
8.
Gene ; 764: 145078, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32858175

RESUMEN

In maize, eat rot and stalk rot caused by Fusarium verticillioides and Fusarium graminearum lead to contamination of moldy grains to produce mycotoxins. Identification of resistance genes against these pathogens for maize breeding is an effective way for disease control. Several 2-oxoglutarate-dependent dioxygenase (2OGD) proteins have been found to confer resistance to different pathogens in diverse plant species. However, little is known about the 2OGD superfamily in maize. Here, we identified 103 putative 2OGD genes in maize from a genome-wide analysis, and divided them into three classes - DOXA, DOXB, and DOXC. We further comprehensively investigated their gene structure, chromosome distribution, phylogenetic tree, gene-function enrichment, and expression profiles among different tissues. The genes encoding three 2OGD proteins, ACO, F3H, and NCS involved in ethylene biosynthesis, flavonoids biosynthesis, and alkaloids biosynthesis pathways, respectively, were identified to be induced by F. verticillioides and F. graminearum. The promoters of the three genes contain the binding sites for the transcription factor ZmDOF and ZmHSF, which are also induced by the two pathogens. The results imply that the three 2OGDs and the two transcription factors might be involved in the resistance to the two pathogens. This study provided a comprehensive understanding of the 2OGD superfamily in maize and laid the foundation for the further functional analysis of their roles in maize resistance to eat rot and stalk rot.


Asunto(s)
Dioxigenasas/genética , Fusarium/inmunología , Proteínas de Plantas/genética , Zea mays/fisiología , Secuencia de Bases/genética , Sitios de Unión/genética , Cromosomas de las Plantas/genética , Coenzimas/metabolismo , Secuencia Conservada/genética , Dioxigenasas/inmunología , Dioxigenasas/metabolismo , Resistencia a la Enfermedad/genética , Evolución Molecular , Fusarium/patogenicidad , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/fisiología , Estudio de Asociación del Genoma Completo , Ácidos Cetoglutáricos/metabolismo , Filogenia , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/inmunología , Proteínas de Plantas/metabolismo , Tallos de la Planta/enzimología , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/microbiología , Regiones Promotoras Genéticas/genética , RNA-Seq , Factores de Transcripción/metabolismo , Zea mays/microbiología
9.
Viruses ; 13(1)2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-33375201

RESUMEN

Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.


Asunto(s)
Dermatitis Atópica/etiología , Dermatitis Atópica/terapia , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/terapia , Fagos de Staphylococcus/fisiología , Staphylococcus aureus/virología , Staphylococcus epidermidis/fisiología , Antibiosis , Bacteriólisis , Biopsia , Terapia Combinada , Dermatitis Atópica/patología , Resistencia a la Enfermedad/genética , Interacciones Huésped-Patógeno , Humanos , Terapia de Fagos , Infecciones Estafilocócicas/patología
10.
PLoS One ; 15(12): e0243445, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33338052

RESUMEN

Pierce's disease (PD) caused by the bacterium Xylella fastidiosa is a deadly disease of grapevines. This study used 20 SSR markers to genotype 326 accessions of grape species collected from the southeastern and southwestern United States, Mexico and Costa Rica. Two hundred sixty-six of these accessions, and an additional 12 PD resistant hybrid cultivars developed from southeastern US grape species, were evaluated for PD resistance. Disease resistance was evaluated by quantifying the level of bacteria in stems and measuring PD symptoms on the canes and leaves. Both Bayesian clustering and principal coordinate analyses identified two groups with an east-west divide: group 1 consisted of grape species from the southeastern US and Mexico, and group 2 consisted of accessions collected from the southwestern US and Mexico. The Sierra Madre Oriental mountain range appeared to be a phylogeographic barrier. The state of Texas was identified as a potential hybridization zone. The hierarchal STRUCTURE analysis on each group showed clustering of unique grape species. An east-west divide was also observed for PD resistance. With the exception of Vitis candicans and V. cinerea accessions collected from Mexico, all other grape species as well as the resistant southeastern hybrid cultivars were susceptible to the disease. Southwestern US grape accessions from drier desert regions showed stronger resistance to the disease. Strong PD resistance was observed within three distinct genetic clusters of V. arizonica which is adapted to drier environments and hybridizes freely with other species across its wide range.


Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Vitis/crecimiento & desarrollo , Xylella/patogenicidad , Costa Rica , Genotipo , Humanos , Hibridación Genética/genética , México , Enfermedades de las Plantas/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/microbiología , Sudoeste de Estados Unidos , Texas , Vitis/genética , Vitis/microbiología
11.
PLoS One ; 15(10): e0239763, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33027258

RESUMEN

Anthracnose, caused by the fungal pathogen Colletotrichum lindemuthianum, is one of the world's most destructive diseases of common bean. The use of resistant cultivars is the most cost-effective strategy to manage this disease; however, durable resistance is difficult to achieve due to the vast virulence diversity of the anthracnose pathogen. Finding new genes with broad-spectrum resistance increases the prospect of designing an effective anthracnose-management strategy. Genetic analysis confirmed the presence of a single, dominant anthracnose-resistance locus in AC, which we provisionally named Co-AC. Bulk segregant analysis and genetic mapping of two F2 populations from the crosses AC × PI207262 and AC × G 2333 were used to determine the position of the Co-AC locus in a 631 Kbp genomic region flanked by the SNP markers SS56 and SS92 on the lower arm of chromosome Pv01. By genotyping 77 F3 plants from the AC × PI207262 cross using nine additional markers, we fine-mapped the Co-AC locus to a significantly smaller genomic region (9.4 Kbp) flanked by the SNP markers SS102 and SS165. This 9.4 Kbp region harbors three predicted genes based on the common bean reference genome, notably including the gene model Phvul.001G244300, which encodes Clathrin heavy chain 1, a protein that supports specific stomatal regulation functions and might play a role in plant defense signaling. Because the Co-AC resistance locus is linked in cis, it can be selected with great efficiency using molecular markers. These results will be very useful for breeding programs aimed at developing bean cultivars with anthracnose resistance using marker-assisted selection. This study revealed the broad-spectrum resistance of AC to C. lindemuthianum and the existence of the Co-AC anthracnose-resistance locus. Fine mapping positioned this locus in a small genomic region on the lower end of chromosome Pv01 that contained three candidate genes for the Co-AC locus.


Asunto(s)
Resistencia a la Enfermedad/genética , Phaseolus/genética , Cruzamiento/métodos , Mapeo Cromosómico/métodos , Colletotrichum/patogenicidad , Genes de Plantas/genética , Ligamiento Genético/genética , Marcadores Genéticos/genética , Genotipo , Phaseolus/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple/genética
12.
PLoS One ; 15(10): e0240029, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33017405

RESUMEN

Lesion mimic (Lm) mutants display hypersensitive responses (HR) without any pathogen attack; their symptoms are similar to those produced by a pathogen and result in cell death. In wheat, such mutants have been reported to be resistant against leaf rust due to their biotrophic nature. However, Lm mutants tend to encourage spot blotch (SB) disease caused by Bipolarissorokiniana since dead cells facilitate pathogen multiplication. In this study, 289 diverse wheat germplasm lines were phenotyped in three consecutive growing seasons (2012-2015). Genotype data was generated using the Illumina iSelect beadchip assay platform for wheat germplasm lines. A total of 13,589 single-nucleotide polymorphisms (SNPs) were selected andused for further association mapping. Lm was positively associated with Area Under Disease Progress Curve (AUDPC) for SB but negatively with glaucous index (GI), leaf tip necrosis (Ltn) and latent period (LP). Ltn had a negative association with AUDPC and Lm but a positive one with LP. In a genome-wide association study (GWAS), 29 markers were significantly associated with these traits and 27 were an notated. Seven SNP markers associated with Lm were on chromosome 6A; another on 1B was found to be linked with Ltn. Like wise, seven SNP markers were associated with GI; one on chromosome 6A with the others on 6B. Five SNP markers on chromosomes 3B and 3Dwere significantly correlated with LP, while nine SNP markers on chromosomes 5A and 5B were significantly associated with AUDPC for SB. This study is the first to explore the interaction in wheat between Lm mutants and the hemibiotrophic SB pathogen B.sorokiniana.


Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Triticum/genética , Área Bajo la Curva , Basidiomycota/patogenicidad , Mapeo Cromosómico , Estudio de Asociación del Genoma Completo , Genotipo , Desequilibrio de Ligamiento , Fenotipo , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Curva ROC , Estaciones del Año
13.
Nat Commun ; 11(1): 4928, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33004791

RESUMEN

High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.


Asunto(s)
Aclimatación/genética , Cromatina/metabolismo , Grupos Étnicos/genética , Redes Reguladoras de Genes , Modelos Genéticos , Altitud , Mal de Altura/etnología , Mal de Altura/genética , Mal de Altura/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Hipoxia de la Célula/genética , Células Cultivadas , Cromatina/genética , Secuenciación de Inmunoprecipitación de Cromatina , Resistencia a la Enfermedad/genética , Femenino , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Oxígeno/metabolismo , Polimorfismo de Nucleótido Simple , Embarazo , Cultivo Primario de Células , RNA-Seq , Elementos Reguladores de la Transcripción/genética , Selección Genética , Tibet/etnología , Factores de Transcripción/metabolismo , Secuenciación Completa del Genoma
14.
Nat Commun ; 11(1): 4393, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32879321

RESUMEN

Rcr3 is a secreted protease of tomato that is targeted by fungal effector Avr2, a secreted protease inhibitor of the fungal pathogen Cladosporium fulvum. The Avr2-Rcr3 complex is recognized by receptor-like protein Cf-2, triggering hypersensitive cell death (HR) and disease resistance. Avr2 also targets Rcr3 paralog Pip1, which is not required for Avr2 recognition but contributes to basal resistance. Thus, Rcr3 acts as a guarded decoy in this interaction, trapping the fungus into a recognition event. Here we show that Rcr3 evolved > 50 million years ago (Mya), whereas Cf-2 evolved <6Mya by co-opting the pre-existing Rcr3 in the Solanum genus. Ancient Rcr3 homologs present in tomato, potato, eggplants, pepper, petunia and tobacco can be inhibited by Avr2 with the exception of tobacco Rcr3. Four variant residues in Rcr3 promote Avr2 inhibition, but the Rcr3 that co-evolved with Cf-2 lacks three of these residues, indicating that the Rcr3 co-receptor is suboptimal for Avr2 binding. Pepper Rcr3 triggers HR with Cf-2 and Avr2 when engineered for enhanced inhibition by Avr2. Nicotiana benthamiana (Nb) is a natural null mutant carrying Rcr3 and Pip1 alleles with deleterious frame-shift mutations. Resurrected NbRcr3 and NbPip1 alleles were active proteases and further NbRcr3 engineering facilitated Avr2 inhibition, uncoupled from HR signalling. The evolution of a receptor co-opting a conserved pathogen target contrasts with other indirect pathogen recognition mechanisms.


Asunto(s)
Cladosporium , Resistencia a la Enfermedad/genética , Péptido Hidrolasas/genética , Inmunidad de la Planta/genética , Solanum , Tabaco , Cladosporium/genética , Cladosporium/metabolismo , Cladosporium/patogenicidad , Evolución Molecular , Proteínas Fúngicas/metabolismo , Genes de Plantas , Interacciones Huésped-Parásitos , Péptido Hidrolasas/metabolismo , Filogenia , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inhibidores de Proteasas/metabolismo , Solanum/genética , Solanum/metabolismo , Solanum/microbiología , Tabaco/genética , Tabaco/metabolismo , Tabaco/microbiología
15.
Nat Commun ; 11(1): 4447, 2020 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-32895382

RESUMEN

Tea is an economically important plant characterized by a large genome, high heterozygosity, and high species diversity. In this study, we assemble a 3.26-Gb high-quality chromosome-scale genome for the 'Longjing 43' cultivar of Camellia sinensis var. sinensis. Genomic resequencing of 139 tea accessions from around the world is used to investigate the evolution and phylogenetic relationships of tea accessions. We find that hybridization has increased the heterozygosity and wide-ranging gene flow among tea populations with the spread of tea cultivation. Population genetic and transcriptomic analyses reveal that during domestication, selection for disease resistance and flavor in C. sinensis var. sinensis populations has been stronger than that in C. sinensis var. assamica populations. This study provides resources for marker-assisted breeding of tea and sets the foundation for further research on tea genetics and evolution.


Asunto(s)
Camellia sinensis/genética , Resistencia a la Enfermedad/genética , Evolución Molecular , Genoma de Planta/genética , Fitomejoramiento , Domesticación , Perfilación de la Expresión Génica , Genómica , Filogenia , Polimorfismo de Nucleótido Simple
16.
Nat Genet ; 52(10): 1111-1121, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32989321

RESUMEN

Wild tomato species represent a rich gene pool for numerous desirable traits lost during domestication. Here, we exploited an introgression population representing wild desert-adapted species and a domesticated cultivar to establish the genetic basis of gene expression and chemical variation accompanying the transfer of wild-species-associated fruit traits. Transcriptome and metabolome analysis of 580 lines coupled to pathogen sensitivity assays resulted in the identification of genomic loci associated with levels of hundreds of transcripts and metabolites. These associations occurred in hotspots representing coordinated perturbation of metabolic pathways and ripening-related processes. Here, we identify components of the Solanum alkaloid pathway, as well as genes and metabolites involved in pathogen defense and linking fungal resistance with changes in the fruit ripening regulatory network. Our results outline a framework for understanding metabolism and pathogen resistance during tomato fruit ripening and provide insights into key fruit quality traits.


Asunto(s)
Resistencia a la Enfermedad/genética , Lycopersicon esculentum/genética , Metaboloma/genética , Transcriptoma/genética , Alcaloides/genética , Domesticación , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/parasitología , Hongos/genética , Hongos/patogenicidad , Regulación de la Expresión Génica de las Plantas/genética , Lycopersicon esculentum/crecimiento & desarrollo , Lycopersicon esculentum/microbiología , Redes y Vías Metabólicas/genética , Fenotipo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Solanum/genética , Solanum/microbiología
17.
PLoS Biol ; 18(9): e3000783, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32925907

RESUMEN

Plant nucleotide-binding (NB) leucine-rich repeat (LRR) receptor (NLR) proteins function as intracellular immune receptors that perceive the presence of pathogen-derived virulence proteins (effectors) to induce immune responses. The 2 major types of plant NLRs that "sense" pathogen effectors differ in their N-terminal domains: these are Toll/interleukin-1 receptor resistance (TIR) domain-containing NLRs (TNLs) and coiled-coil (CC) domain-containing NLRs (CNLs). In many angiosperms, the RESISTANCE TO POWDERY MILDEW 8 (RPW8)-CC domain containing NLR (RNL) subclass of CNLs is encoded by 2 gene families, ACTIVATED DISEASE RESISTANCE 1 (ADR1) and N REQUIREMENT GENE 1 (NRG1), that act as "helper" NLRs during multiple sensor NLR-mediated immune responses. Despite their important role in sensor NLR-mediated immunity, knowledge of the specific, redundant, and synergistic functions of helper RNLs is limited. We demonstrate that the ADR1 and NRG1 families act in an unequally redundant manner in basal resistance, effector-triggered immunity (ETI) and regulation of defense gene expression. We define RNL redundancy in ETI conferred by some TNLs and in basal resistance against virulent pathogens. We demonstrate that, in Arabidopsis thaliana, the 2 RNL families contribute specific functions in ETI initiated by specific CNLs and TNLs. Time-resolved whole genome expression profiling revealed that RNLs and "classical" CNLs trigger similar transcriptome changes, suggesting that RNLs act like other CNLs to mediate ETI downstream of sensor NLR activation. Together, our genetic data confirm that RNLs contribute to basal resistance, are fully required for TNL signaling, and can also support defense activation during CNL-mediated ETI.


Asunto(s)
Arabidopsis/inmunología , Proteínas NLR/fisiología , Inmunidad de la Planta/genética , Receptores Inmunológicos/fisiología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/fisiología , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Regulación de la Expresión Génica de las Plantas , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/fisiología , Familia de Multigenes/genética , Familia de Multigenes/fisiología , Proteínas NLR/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Plantas Modificadas Genéticamente , Receptores Inmunológicos/genética , Transducción de Señal/genética , Transducción de Señal/inmunología , Transcriptoma
18.
PLoS One ; 15(9): e0239205, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32925954

RESUMEN

Striga is an important biotic factor limiting maize production in sub-Saharan Africa and can cause yield losses as high as 100%. Marker-assisted selection (MAS) approaches hold a great potential for improving Striga resistance but requires identification and use of markers associated with Striga resistance for adequate genetic gains from selection. However, there is no report on the discovery of quantitative trait loci (QTL) for resistance to Striga in maize under artificial field infestation. In the present study, 198 BC1S1 families obtained from a cross involving TZEEI 29 (Striga resistant inbred line) and TZEEI 23 (Striga susceptible inbred line) plus the two parental lines were screened under artificial Striga-infested conditions at two Striga-endemic locations in Nigeria in 2018, to identify QTL associated with Striga resistance indicator traits, including grain yield, ears per plant, Striga damage and number of emerged Striga plants. Genetic map was constructed using 1,386 DArTseq markers distributed across the 10 maize chromosomes, covering 2076 cM of the total genome with a mean spacing of 0.11 cM between the markers. Using composite interval mapping (CIM), fourteen QTL were identified for key Striga resistance/tolerance indicator traits: 3 QTL for grain yield, 4 for ears per plant and 7 for Striga damage at 10 weeks after planting (WAP), across environments. Putative candidate genes which encode major transcription factor families WRKY, bHLH, AP2-EREBPs, MYB, and bZIP involved in plant defense signaling were detected for Striga resistance/tolerance indicator traits. The QTL detected in the present study would be useful for rapid transfer of Striga resistance/tolerance genes into Striga susceptible but high yielding maize genotypes using MAS approaches after validation. Further studies on validation of the QTL in different genetic backgrounds and in different environments would help verify their reproducibility and effective use in breeding for Striga resistance/tolerance.


Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Sitios de Carácter Cuantitativo , Zea mays/genética , Nigeria , Striga
20.
Phytopathology ; 110(10): 1721-1726, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32915112

RESUMEN

Stem rust is an important disease of cultivated oat (Avena sativa) caused by Puccinia graminis f. sp. avenae. In North America, host resistance is the primary strategy to control this disease and is conferred by a relatively small number of resistance genes. Pg2 is a widely deployed stem rust resistance gene that originates from cultivated oat. Oat breeders wish to develop cultivars with multiple Pg genes to slow the breakdown of single gene resistance, and often require DNA markers suited for marker-assisted selection. Our objectives were to (i) construct high density linkage maps for a major oat stem rust resistance gene using three biparental mapping populations, (ii) develop Kompetitive allele-specific PCR (KASP) assays for Pg2-linked single-nucleotide polymorphisms (SNPs), and (iii) test the prediction accuracy of those markers with a diverse panel of spring oat lines and cultivars. Genotyping-by-sequencing SNP markers linked to Pg2 were identified in an AC Morgan/CDC Morrison recombinant inbred line (RIL) population. Pg2-linked SNPs were then analyzed in an AC Morgan/RL815 F2 population and an AC Morgan/CDC Dancer RIL population. Linkage analysis identified a common location for Pg2 in all three populations on linkage group Mrg20 of the oat consensus genetic map. The most predictive markers were identified and converted to KASP assays for use in oat breeding programs. When used in combination, the KASP assays for the SNP loci avgbs2_126549.1.46 and avgbs_cluster_23819.1.27 were highly predictive of Pg2 status in panel of 54 oat breeding lines and cultivars.


Asunto(s)
Avena/genética , Basidiomycota , Mapeo Cromosómico , Resistencia a la Enfermedad/genética , Ligamiento Genético , Humanos , América del Norte , Enfermedades de las Plantas , Polimorfismo de Nucleótido Simple/genética
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