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1.
Proc Natl Acad Sci U S A ; 119(24): e2200016119, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35666863

RESUMO

The polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000- to 115,000-y-old polar bear from the Svalbard Archipelago using a 10× coverage genome sequence and 10 new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bear's lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 y. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published work. These findings may have implications for our understanding of climate change impacts: Polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks but also been the recipient of generalist, boreal genetic variants from brown bears during critical phases of Northern Hemisphere glacial oscillations.


Assuntos
Evolução Biológica , Hibridização Genética , Ursidae , Animais , Fluxo Gênico , Genoma/genética , Filogenia , Ursidae/genética
2.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35131944

RESUMO

The troposphere constitutes the final frontier of global ecosystem research due to technical challenges arising from its size, low biomass, and gaseous state. Using a vertical testing array comprising a meteorological tower and a research aircraft, we conducted synchronized measurements of meteorological parameters and airborne biomass (n = 480) in the vertical air column up to 3,500 m. The taxonomic analysis of metagenomic data revealed differing patterns of airborne microbial community composition with respect to time of day and height above ground. The temporal and spatial resolution of our study demonstrated that the diel cycle of airborne microorganisms is a ground-based phenomenon that is entirely absent at heights >1,000 m. In an integrated analysis combining meteorological and biological data, we demonstrate that atmospheric turbulence, identified by potential temperature and high-frequency three-component wind measurements, is the key driver of bioaerosol dynamics in the lower troposphere. Multivariate regression analysis shows that at least 50% of identified airborne microbial taxa (n = ∼10,000) are associated with either ground or height, allowing for an understanding of dispersal patterns of microbial taxa in the vertical air column. Due to the interconnectedness of atmospheric turbulence and temperature, the dynamics of microbial dispersal are likely to be impacted by rising global temperatures, thereby also affecting ecosystems on the planetary surface.


Assuntos
Microbiologia do Ar , Bactérias/classificação , Bactérias/isolamento & purificação , Aerossóis , Altitude , Atmosfera , Humanos
3.
Proc Natl Acad Sci U S A ; 118(26)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34162703

RESUMO

No endemic Madagascar animal with body mass >10 kg survived a relatively recent wave of extinction on the island. From morphological and isotopic analyses of skeletal "subfossil" remains we can reconstruct some of the biology and behavioral ecology of giant lemurs (primates; up to ∼160 kg) and other extraordinary Malagasy megafauna that survived into the past millennium. Yet, much about the evolutionary biology of these now-extinct species remains unknown, along with persistent phylogenetic uncertainty in some cases. Thankfully, despite the challenges of DNA preservation in tropical and subtropical environments, technical advances have enabled the recovery of ancient DNA from some Malagasy subfossil specimens. Here, we present a nuclear genome sequence (∼2× coverage) for one of the largest extinct lemurs, the koala lemur Megaladapis edwardsi (∼85 kg). To support the testing of key phylogenetic and evolutionary hypotheses, we also generated high-coverage nuclear genomes for two extant lemurs, Eulemur rufifrons and Lepilemur mustelinus, and we aligned these sequences with previously published genomes for three other extant lemurs and 47 nonlemur vertebrates. Our phylogenetic results confirm that Megaladapis is most closely related to the extant Lemuridae (typified in our analysis by E. rufifrons) to the exclusion of L. mustelinus, which contradicts morphology-based phylogenies. Our evolutionary analyses identified significant convergent evolution between M. edwardsi and an extant folivore (a colobine monkey) and an herbivore (horse) in genes encoding proteins that function in plant toxin biodegradation and nutrient absorption. These results suggest that koala lemurs were highly adapted to a leaf-based diet, which may also explain their convergent craniodental morphology with the small-bodied folivore Lepilemur.


Assuntos
Núcleo Celular/genética , Extinção Biológica , Genoma , Lemur/genética , Filogenia , Aminoácidos/genética , Animais , Sequência de Bases , Evolução Molecular , Genômica , Herbivoria/fisiologia
4.
Infect Immun ; 90(8): e0006122, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35913171

RESUMO

Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a plac-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo plac-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the plac-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea.


Assuntos
Pseudomonas aeruginosa , Sistemas de Secreção Tipo III , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica , Camundongos , Pseudomonas aeruginosa/genética , Sistemas de Secreção Tipo III/genética , Sistemas de Secreção Tipo III/metabolismo
5.
Indoor Air ; 32(1): e12930, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519380

RESUMO

Reliable methods to detect the presence of SARS-CoV-2 at venues where people gather are essential for epidemiological surveillance to guide public policy. Communal screening of air in a highly crowded space has the potential to provide early warning on the presence and potential transmission of SARS-CoV-2 as suggested by studies early in the epidemic. As hospitals and public facilities apply varying degrees of restrictions and regulations, it is important to provide multiple methodological options to enable environmental SARS-CoV-2 surveillance under different conditions. This study assessed the feasibility of using high-flowrate air samplers combined with RNA extraction kit designed for environmental sample to perform airborne SARS-CoV-2 surveillance in hospital setting, tested by RT-qPCR. The success rate of the air samples in detecting SARS-CoV-2 was then compared with surface swab samples collected in the same proximity. Additionally, positive RT-qPCR samples underwent viral culture to assess the viability of the sampled SARS-CoV-2. The study was performed in inpatient ward environments of a quaternary care university teaching hospital in Singapore housing active COVID-19 patients within the period of February to May 2020. Two types of wards were tested, naturally ventilated open-cohort ward and mechanically ventilated isolation ward. Distances between the site of air sampling and the patient cluster in the investigated wards were also recorded. No successful detection of airborne SARS-CoV-2 was recorded when 50 L/min air samplers were used. Upon increasing the sampling flowrate to 150 L/min, our results showed a high success rate in detecting the presence of SARS-CoV-2 from the air samples (72%) compared to the surface swab samples (9.6%). The positive detection rate of the air samples along with the corresponding viral load could be associated with the distance between sampling site and patient. The furthest distance from patient with PCR-positive air samples was 5.5 m. The airborne SARS-CoV-2 detection was comparable between the two types of wards with 60%-87.5% success rate. High prevalence of the virus was found in toilet areas, both on surfaces and in air. Finally, no successful culture attempt was recorded from the environmental air or surface samples.


Assuntos
Microbiologia do Ar , Poluição do Ar em Ambientes Fechados , Hospitais , SARS-CoV-2/isolamento & purificação , COVID-19 , Humanos , RNA Viral , Manejo de Espécimes
6.
Proc Natl Acad Sci U S A ; 116(46): 23299-23308, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31659049

RESUMO

The atmosphere is vastly underexplored as a habitable ecosystem for microbial organisms. In this study, we investigated 795 time-resolved metagenomes from tropical air, generating 2.27 terabases of data. Despite only 9 to 17% of the generated sequence data currently being assignable to taxa, the air harbored a microbial diversity that rivals the complexity of other planetary ecosystems. The airborne microbial organisms followed a clear diel cycle, possibly driven by environmental factors. Interday taxonomic diversity exceeded day-to-day and month-to-month variation. Environmental time series revealed the existence of a large core of microbial taxa that remained invariable over 13 mo, thereby underlining the long-term robustness of the airborne community structure. Unlike terrestrial or aquatic environments, where prokaryotes are prevalent, the tropical airborne biomass was dominated by DNA from eukaryotic phyla. Specific fungal and bacterial species were strongly correlated with temperature, humidity, and CO2 concentration, making them suitable biomarkers for studying the bioaerosol dynamics of the atmosphere.


Assuntos
Microbiologia do Ar , Microbiota , Clima Tropical , Poluentes Atmosféricos/análise , Ritmo Circadiano , Ecossistema , Metagenoma , Modelos Biológicos , Singapura
7.
BMC Microbiol ; 21(1): 191, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172012

RESUMO

BACKGROUND: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. RESULTS: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. CONCLUSIONS: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. TRIAL REGISTRATION: The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.


Assuntos
Bactérias/genética , Cesárea/efeitos adversos , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Metagenoma/genética , Biodiversidade , Método Duplo-Cego , Humanos , Lactente , Recém-Nascido
8.
Indoor Air ; 31(5): 1639-1644, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33876847

RESUMO

Facing shortages of personal protective equipment, some clinicians have advocated the use of barrier enclosures (typically mounted over the head, with and without suction) to contain aerosol emissions from coronavirus disease 2019 (COVID-19) patients. There is, however, little evidence for its usefulness. To test the effectiveness of such a device, we built a manikin that can expire micron-sized aerosols at flow rates close to physiological conditions. We then placed the manikin inside the enclosure and used a laser sheet to visualize the aerosol leaking out. We show that with sufficient suction, it is possible to effectively contain aerosol from the manikin, reducing aerosol exposure outside the enclosure by 99%. In contrast, a passive barrier without suction only reduces aerosol exposure by 60%.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Infecções/métodos , Humanos , Modelos Anatômicos , SARS-CoV-2 , Sucção/métodos
9.
Am J Respir Crit Care Med ; 202(3): 433-447, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320621

RESUMO

Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown.Objectives: To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing.Methods: Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads. Respiratory and device-associated microbiomes were evaluated on the basis of taxonomical classification and functional annotation including the Comprehensive Antibiotic Resistance Database to determine airway resistomes. Co-occurrence networks of gene-microbe association were constructed to determine potential microbial sources of the airway resistome. Paired patient-inhaler metagenomes were compared (n = 31) to assess for the presence of airway-environment overlap in microbiomes and/or resistomes.Measurements and Main Results: Airway metagenomes exhibit taxonomic and metabolic diversity and distinct antimicrobial resistance patterns. A "core" airway resistome dominated by macrolide but with high prevalence of ß-lactam, fluoroquinolone, and tetracycline resistance genes exists and is independent of disease status or antibiotic exposure. Streptococcus and Actinomyces are key potential microbial reservoirs of macrolide resistance including the ermX, ermF, and msrD genes. Significant patient-inhaler overlap in airway microbiomes and their resistomes is identified where the latter may be a proxy for airway microbiome assessment in chronic respiratory disease.Conclusions: Metagenomic analysis of the airway reveals a core macrolide resistome harbored by the host microbiome.


Assuntos
Asma/microbiologia , Bronquiectasia/microbiologia , Farmacorresistência Bacteriana/genética , Disbiose/microbiologia , Macrolídeos , Metagenômica , Microbiota/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Estudos de Casos e Controles , Feminino , Fluoroquinolonas , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores/microbiologia , Índice de Gravidade de Doença , Resistência a Tetraciclina/genética , Resistência beta-Lactâmica/genética
10.
BMC Genomics ; 21(1): 160, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059640

RESUMO

BACKGROUND: Climate plays an essential role in forest health, and climate change may increase forest productivity losses due to abiotic and biotic stress. Increased temperature leads to the increased formation of ozone (O3). Ozone is formed by the interaction of sunlight, molecular oxygen and by the reactions of chemicals commonly found in industrial and automobile emissions such as nitrogen oxides and volatile organic compounds. Although it is well known that productivity of Northern red oak (Quercus rubra) (NRO), an ecologically and economically important species in the forests of eastern North America, is reduced by exposure to O3, limited information is available on its responses to exogenous stimuli at the level of gene expression. RESULTS: RNA sequencing yielded more than 323 million high-quality raw sequence reads. De novo assembly generated 52,662 unigenes, of which more than 42,000 sequences could be annotated through homology-based searches. A total of 4140 differential expressed genes (DEGs) were detected in response to O3 stress, as compared to their respective controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the O3-response DEGs revealed perturbation of several biological pathways including energy, lipid, amino acid, carbohydrate and terpenoid metabolism as well as plant-pathogen interaction. CONCLUSION: This study provides the first reference transcriptome for NRO and initial insights into the genomic responses of NRO to O3. Gene expression profiling reveals altered primary and secondary metabolism of NRO seedlings, including known defense responses such as terpenoid biosynthesis.


Assuntos
Perfilação da Expressão Gênica , Ozônio/metabolismo , Quercus/genética , Quercus/metabolismo , Estresse Fisiológico , Transcriptoma , Vias Biossintéticas , Biologia Computacional/métodos , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Interações Hospedeiro-Patógeno , Anotação de Sequência Molecular , Transdução de Sinais
11.
Eur Respir J ; 56(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32341102

RESUMO

INTRODUCTION: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear. METHODS: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome. RESULTS: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD. CONCLUSION: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD.


Assuntos
Poluição do Ar em Ambientes Fechados , Doença Pulmonar Obstrutiva Crônica , Poluição do Ar em Ambientes Fechados/análise , Alérgenos , Fungos , Hong Kong , Humanos , Malásia/epidemiologia , Singapura
12.
BMC Infect Dis ; 20(1): 312, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345218

RESUMO

BACKGROUND: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. METHODS: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. RESULTS: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. CONCLUSION: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Eczema/diagnóstico , Microbioma Gastrointestinal/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Eczema/etiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Estudos Longitudinais , Masculino , Risco , beta-Lactamases/genética , beta-Lactamases/metabolismo , beta-Lactamas/farmacologia
13.
Cell Mol Life Sci ; 76(21): 4341-4354, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31119300

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that is thought to be reversible by changing the diet. To examine the impact of dietary changes on progression and cure of NAFLD, we fed mice a high-fat diet (HFD) or high-fructose diet (HFrD) for 9 weeks, followed by an additional 9 weeks, where mice were given normal chow diet. As predicted, the diet-induced NAFLD elicited changes in glucose tolerance, serum cholesterol, and triglyceride levels in both diet groups. Moreover, the diet-induced NAFLD phenotype was reversed, as measured by the recovery of glucose intolerance and high cholesterol levels when mice were given normal chow diet. However, surprisingly, the elevated serum triglyceride levels persisted. Metagenomic analysis revealed dietary-induced changes of microbiome composition, some of which remained altered even after reversing the diet to normal chow, as illustrated by species of the Odoribacter genus. Genome-wide DNA methylation analysis revealed a "priming effect" through changes in DNA methylation in key liver genes. For example, the lipid-regulating gene Apoa4 remained hypomethylated in both groups even after introduction to normal chow diet. Our results support that dietary change, in part, reverses the NAFLD phenotype. However, some diet-induced effects remain, such as changes in microbiome composition, elevated serum triglyceride levels, and hypomethylation of key liver genes. While the results are correlative in nature, it is tempting to speculate that the dietary-induced changes in microbiome composition may in part contribute to the persistent epigenetic modifications in the liver.


Assuntos
Metilação de DNA , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Metilação de DNA/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia
14.
Proc Natl Acad Sci U S A ; 114(22): E4435-E4441, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28507139

RESUMO

Utricularia gibba, the humped bladderwort, is a carnivorous plant that retains a tiny nuclear genome despite at least two rounds of whole genome duplication (WGD) since common ancestry with grapevine and other species. We used a third-generation genome assembly with several complete chromosomes to reconstruct the two most recent lineage-specific ancestral genomes that led to the modern U. gibba genome structure. Patterns of subgenome dominance in the most recent WGD, both architectural and transcriptional, are suggestive of allopolyploidization, which may have generated genomic novelty and led to instantaneous speciation. Syntenic duplicates retained in polyploid blocks are enriched for transcription factor functions, whereas gene copies derived from ongoing tandem duplication events are enriched in metabolic functions potentially important for a carnivorous plant. Among these are tandem arrays of cysteine protease genes with trap-specific expression that evolved within a protein family known to be useful in the digestion of animal prey. Further enriched functions among tandem duplicates (also with trap-enhanced expression) include peptide transport (intercellular movement of broken-down prey proteins), ATPase activities (bladder-trap acidification and transmembrane nutrient transport), hydrolase and chitinase activities (breakdown of prey polysaccharides), and cell-wall dynamic components possibly associated with active bladder movements. Whereas independently polyploid Arabidopsis syntenic gene duplicates are similarly enriched for transcriptional regulatory activities, Arabidopsis tandems are distinct from those of U. gibba, while still metabolic and likely reflecting unique adaptations of that species. Taken together, these findings highlight the special importance of tandem duplications in the adaptive landscapes of a carnivorous plant genome.


Assuntos
Carnivoridade/fisiologia , Genoma de Planta , Lamiales/genética , Lamiales/fisiologia , Adaptação Fisiológica/genética , Cisteína Proteases/química , Cisteína Proteases/genética , Evolução Molecular , Duplicação Gênica , Modelos Moleculares , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Poliploidia , Análise de Sequência de DNA , Sintenia
15.
Mycopathologia ; 185(3): 591-594, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32270395

RESUMO

Penicillium oxalicum strain SGAir0226 was isolated from a tropical air sample collected in Singapore. The complete genome was assembled from long reads obtained from single-molecule real-time sequencing and was further polished and error corrected using short read sequencing data. The assembly comprises 20 contigs with a total length of 30.7 Mb. The genome was predicted to contain 8310 protein-coding genes, 237 tRNAs and 83 rRNAs.


Assuntos
Microbiologia do Ar , Genoma Fúngico , Penicillium/genética , RNA Fúngico/química , Anotação de Sequência Molecular , Penicillium/química , Penicillium/classificação , Penicillium/isolamento & purificação , Filogenia , RNA Fúngico/isolamento & purificação , RNA Ribossômico/química , RNA Ribossômico/isolamento & purificação , RNA de Transferência/química , RNA de Transferência/isolamento & purificação , Singapura , Clima Tropical
16.
Mycopathologia ; 185(2): 405-408, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108289

RESUMO

Aspergillus terreus species complex is an opportunistic fungal pathogen increasingly implicated in invasive infection, as well as chronic respiratory disease. Currently, an understanding of A. terreus pathogenicity is impeded by a limited number of whole-genome sequences of this fungal pathogen. We here describe a high-quality whole-genome assembly of European A. terreus clinical isolate M6925, derived by single-molecule real-time sequencing with short-read polishing.


Assuntos
Aspergillus , Genoma Fúngico/genética , Sequenciamento Completo do Genoma , Aspergillus/classificação , Aspergillus/genética , Humanos
17.
Appl Environ Microbiol ; 85(10)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30850427

RESUMO

Although the ubiquitous bacterial secondary messenger cyclic diguanylate (c-di-GMP) has important cellular functions in a wide range of bacteria, its function in the model plant pathogen Pseudomonas syringae remains largely elusive. To this end, we overexpressed Escherichia coli diguanylate cyclase (YedQ) and phosphodiesterase (YhjH) in P. syringae, resulting in high and low in vivo levels of c-di-GMP, respectively. Via genome-wide RNA sequencing of these two strains, we found that c-di-GMP regulates (i) fliN, fliE, and flhA, which are associated with flagellar assembly; (ii) alg8 and alg44, which are related to the exopolysaccharide biosynthesis pathway; (iii) pvdE, pvdP, and pvsA, which are associated with the siderophore biosynthesis pathway; and (iv) sodA, which encodes a superoxide dismutase. In particular, we identified three promoters that are sensitive to elevated levels of c-di-GMP and inserted them into luciferase-based reporters that respond effectively to the c-di-GMP levels in P. syringae; these promoters could be useful in the measurement of in vivo levels of c-di-GMP in real time. Further phenotypic assays validated the RNA sequencing (RNA-seq) results and confirmed the effect on c-di-GMP-associated pathways, such as repressing the type III secretion system (T3SS) and motility while inducing biofilm production, siderophore production, and oxidative stress resistance. Taken together, these results demonstrate that c-di-GMP regulates the virulence and stress response in P. syringae, which suggests that tuning its level could be a new strategy to protect plants from attacks by this pathogen.IMPORTANCE The present work comprehensively analyzed the transcriptome and phenotypes that were regulated by c-di-GMP in P. syringae Given that the majority of diguanylate cyclases and phosphodiesterases have not been characterized in P. syringae, this work provided a very useful database for the future study on regulatory mechanism (especially its relationship with T3SS) of c-di-GMP in P. syringae In particular, we identified three promoters that were sensitive to elevated c-di-GMP levels and inserted them into luciferase-based reporters that effectively respond to intracellular levels of c-di-GMP in P. syringae, which could be used as an economic and efficient way to measure relative c-di-GMP levels in vivo in the future.


Assuntos
GMP Cíclico/análogos & derivados , Pleiotropia Genética , Pseudomonas syringae/genética , GMP Cíclico/genética , GMP Cíclico/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/metabolismo , Microrganismos Geneticamente Modificados/patogenicidade , Pseudomonas syringae/metabolismo , Pseudomonas syringae/patogenicidade , Virulência/genética
18.
Genet Res (Camb) ; 101: e5, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30912487

RESUMO

GenomeAsia100K is a human genome project based at Nanyang Technological University in Singapore that aims to sequence one hundred thousand Asian genomes in an effort that addresses an ethnic bias towards Western populations in previous genomic research. GenomeAsia100K consists of a team of bioinformaticians, statisticians and population geneticists, and was initiated by the Nanyang Technological University in collaboration with industrial partners MedGenome (an Indian R&D company specializing in genomic data) and the California Biotech company Genentech. The GenomeAsia100K project is amongst the most ambitious precision medicine projects to date but it is not clear how the project will challenge or reshape understandings of ethnic and racial differences in Asian populations. Ian McGonigle, a scientist and cultural anthropologist, sat down with geneticist Stephan C. Schuster, the scientific chairman of GenomeAsia100K, to discuss the project and the implications of genomics for social identity in the 21st century.


Assuntos
Povo Asiático/genética , Etnicidade/genética , Genômica/métodos , Genoma/genética , Genoma Humano/genética , Genômica/tendências , Humanos
19.
Nature ; 498(7452): 94-8, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23665961

RESUMO

It has been argued that the evolution of plant genome size is principally unidirectional and increasing owing to the varied action of whole-genome duplications (WGDs) and mobile element proliferation. However, extreme genome size reductions have been reported in the angiosperm family tree. Here we report the sequence of the 82-megabase genome of the carnivorous bladderwort plant Utricularia gibba. Despite its tiny size, the U. gibba genome accommodates a typical number of genes for a plant, with the main difference from other plant genomes arising from a drastic reduction in non-genic DNA. Unexpectedly, we identified at least three rounds of WGD in U. gibba since common ancestry with tomato (Solanum) and grape (Vitis). The compressed architecture of the U. gibba genome indicates that a small fraction of intergenic DNA, with few or no active retrotransposons, is sufficient to regulate and integrate all the processes required for the development and reproduction of a complex organism.


Assuntos
Evolução Molecular , Genoma de Planta/genética , Magnoliopsida/genética , DNA Intergênico/genética , Duplicação Gênica/genética , Genes de Plantas/genética , Modelos Genéticos , Solanum/genética , Sintenia/genética , Vitis/genética
20.
Proc Natl Acad Sci U S A ; 113(45): E7010-E7019, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27791104

RESUMO

Horizontal gene transfer (HGT) is the transfer of genetic material across species boundaries and has been a driving force in prokaryotic evolution. HGT involving eukaryotes appears to be much less frequent, and the functional implications of HGT in eukaryotes are poorly understood. We test the hypothesis that parasitic plants, because of their intimate feeding contacts with host plant tissues, are especially prone to horizontal gene acquisition. We sought evidence of HGTs in transcriptomes of three parasitic members of Orobanchaceae, a plant family containing species spanning the full spectrum of parasitic capabilities, plus the free-living Lindenbergia Following initial phylogenetic detection and an extensive validation procedure, 52 high-confidence horizontal transfer events were detected, often from lineages of known host plants and with an increasing number of HGT events in species with the greatest parasitic dependence. Analyses of intron sequences in putative donor and recipient lineages provide evidence for integration of genomic fragments far more often than retro-processed RNA sequences. Purifying selection predominates in functionally transferred sequences, with a small fraction of adaptively evolving sites. HGT-acquired genes are preferentially expressed in the haustorium-the organ of parasitic plants-and are strongly biased in predicted gene functions, suggesting that expression products of horizontally acquired genes are contributing to the unique adaptive feeding structure of parasitic plants.

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