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1.
Nat Med ; 25(12): 1865-1872, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792456

RESUMO

Viruses are implicated in autoimmune destruction of pancreatic islet ß cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect ß cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. ß cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to ß cells between serotypes and within the same serotype9,10. In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.


Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/virologia , Enterovirus/isolamento & purificação , RNA Viral/isolamento & purificação , Adolescente , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Enterovirus/imunologia , Enterovirus/patogenicidade , Fezes/virologia , Feminino , Humanos , Lactente , Insulina/metabolismo , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/virologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/virologia , Masculino , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/virologia
2.
Microbiome ; 7(1): 145, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699146

RESUMO

BACKGROUND: Regulatory T cell (Treg) deficiency leads to IPEX syndrome, a lethal autoimmune disease, in Human and mice. Dysbiosis of the gut microbiota in Treg-deficient scurfy (SF) mice has been described, but to date, the role of the gut microbiota remains to be determined. RESULTS: To examine how antibiotic-modified microbiota can inhibit Treg deficiency-induced lethal inflammation in SF mice, Treg-deficient SF mice were treated with three different antibiotics. Different antibiotics resulted in distinct microbiota and metabolome changes and led to varied efficacy in prolonging lifespan and reducing inflammation in the liver and lung. Moreover, antibiotics altered plasma levels of several cytokines, especially IL-6. By analyzing gut microbiota and metabolome, we determined the microbial and metabolomic signatures which were associated with the antibiotics. Remarkably, antibiotic treatments restored the levels of several primary and secondary bile acids, which significantly reduced IL-6 expression in RAW macrophages in vitro. IL-6 blockade prolonged lifespan and inhibited inflammation in the liver and lung. By using IL-6 knockout mice, we further identified that IL-6 deletion provided a significant portion of the protection against inflammation induced by Treg dysfunction. CONCLUSION: Our results show that three antibiotics differentially prolong survival and inhibit lethal inflammation in association with a microbiota-IL-6 axis. This pathway presents a potential avenue for treating Treg deficiency-mediated autoimmune disorders.

3.
Am J Physiol Gastrointest Liver Physiol ; 317(6): G824-G838, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31482733

RESUMO

Early administration of Lactobacillus reuteri DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis. We gavaged LR (107 colony-forming units/day, daily) to C57BL/6J mice at age of day 8 for 2 wk. Both male and female mice were investigated in these experiments. We found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+ regulatory T cells (Tregs) in the intestine. LR also increased bacterial diversity and the relative abundance of p_Firmicutes, f_Lachnospiraceae, f_Ruminococcaceae, and genera Clostridium and Candidatus arthromitus, while decreasing the relative abundance of p_Bacteriodetes, f_Bacteroidaceae, f_Verrucomicrobiaceae, and genera Bacteroides, Ruminococcus, Akkermansia, and Sutterella. Finally, LR exerted a major impact on the plasma metabolome, upregulating amino acid metabolites formed via the urea, tricarboxylic acid, and methionine cycles and increasing tryptophan metabolism. In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health.NEW & NOTEWORTHY Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulates plasma metabolites that are involved in the urea cycle, the TCA cycle, methionine methylation, and the polyamine pathway. Herein, we show that LR given to newborn mice specifically increases levels of tryptophan metabolites and the purine nucleoside adenosine that are known to enhance tolerance to inflammatory stimuli.

4.
Front Immunol ; 10: 385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899262

RESUMO

The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probiotic Lactobacillus reuteri DSM 17938 (L. reuteri) ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by TH17 and TH1 cells. We discovered that L. reuteri treatment reduced TH1/TH17 cells and their associated cytokines IFN-γ/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored by L. reuteri treatment. Taxonomy-based analysis of gut microbiota showed that three "beneficial" genera Bifidobacterium, Prevotella, and Lactobacillus were negatively correlated with EAE clinical severity, whereas the genera Anaeroplasma, Rikenellaceae, and Clostridium were positively correlated with disease severity. Notably, L. reuteri treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probiotic L. reuteri changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.

5.
Proc Natl Acad Sci U S A ; 115(12): 3096-3101, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29507206

RESUMO

Many microbes engage in social interactions. Some of these have come to play an important role in the study of cooperation and conflict, largely because, unlike most animals, they can be genetically manipulated and experimentally evolved. However, whereas animal social behavior can be observed and assessed in natural environments, microbes usually cannot, so we know little about microbial social adaptations in nature. This has led to some difficult-to-resolve controversies about social adaptation even for well-studied traits such as bacterial quorum sensing, siderophore production, and biofilms. Here we use molecular signatures of population genetics and molecular evolution to address controversies over the existence of altruism and cheating in social amoebas. First, we find signatures of rapid adaptive molecular evolution that are consistent with social conflict being a significant force in nature. Second, we find population-genetic signatures of purifying selection to support the hypothesis that the cells that form the sterile stalk evolve primarily through altruistic kin selection rather than through selfish direct reproduction. Our results show how molecular signatures can provide insight into social adaptations that cannot be observed in their natural context, and they support the hypotheses that social amoebas in the wild are both altruists and cheaters.


Assuntos
Dictyostelium/genética , Dictyostelium/fisiologia , Adaptação Fisiológica , Evolução Molecular , Regulação da Expressão Gênica , Variação Genética , Genoma de Protozoário , Seleção Genética
6.
J Exp Med ; 214(1): 107-123, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27994068

RESUMO

Regulatory T (T reg) cell deficiency causes lethal, CD4+ T cell-driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells. It is currently unclear if T reg cell deficiency-mediated autoimmune disorders can be treated by targeting the enteric microbiota. Here, we demonstrate that Foxp3+ T reg cell deficiency results in gut microbial dysbiosis and autoimmunity over the lifespan of scurfy (SF) mouse. Remodeling microbiota with Lactobacillus reuteri prolonged survival and reduced multiorgan inflammation in SF mice. L. reuteri changed the metabolomic profile disrupted by T reg cell deficiency, and a major effect was to restore levels of the purine metabolite inosine. Feeding inosine itself prolonged life and inhibited multiorgan inflammation by reducing Th1/Th2 cells and their associated cytokines. Mechanistically, the inhibition of inosine on the differentiation of Th1 and Th2 cells in vitro depended on adenosine A2A receptors, which were also required for the efficacy of inosine and of L. reuteri in vivo. These results reveal that the microbiota-inosine-A2A receptor axis might represent a potential avenue for combatting autoimmune diseases mediated by T reg cell dysfunction.


Assuntos
Autoimunidade , Microbioma Gastrointestinal , Lactobacillus reuteri , Receptor A2A de Adenosina/fisiologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Feminino , Inosina/farmacologia , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Células Th1/citologia , Células Th2/citologia
7.
Sci Rep ; 5: 10604, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26040234

RESUMO

Dietary fibers are increasingly appreciated as beneficial nutritional components. However, a requisite role of gut microbiota in fiber function and the overall impact of fibers on metabolomic flux remain unclear. We herein showed enhancing effects of a soluble resistant maltodextrin (RM) on glucose homeostasis in mouse metabolic disease models. Remarkably, fecal microbiota transplantation (FMT) caused pronounced and time-dependent improvement in glucose tolerance in RM recipient mice, indicating a causal relationship between microbial remodeling and metabolic efficacy. Microbial 16S sequencing revealed transmissible taxonomic changes correlated with improved metabolism, notably enrichment of probiotics and reduction of Alistipes and Bacteroides known to associate with high fat/protein diets. Metabolomic profiling further illustrated broad changes, including enrichment of phenylpropionates and decreases in key intermediates of glucose utilization, cholesterol biosynthesis and amino acid fermentation. These studies elucidate beneficial roles of RM-dependent microbial remodeling in metabolic homeostasis, and showcase prevalent health-promoting potentials of dietary fibers.


Assuntos
Fibras na Dieta , Microbioma Gastrointestinal , Homeostase , Metaboloma , Metabolômica , Animais , Biomarcadores , Glicemia , Análise por Conglomerados , Modelos Animais de Doenças , Doenças Metabólicas/metabolismo , Doenças Metabólicas/microbiologia , Camundongos , Polissacarídeos/metabolismo
8.
Curr Biol ; 25(12): 1661-5, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26051890

RESUMO

Cooperative systems are susceptible to invasion by selfish individuals that profit from receiving the social benefits but fail to contribute. These so-called "cheaters" can have a fitness advantage in the laboratory, but it is unclear whether cheating provides an important selective advantage in nature. We used a population genomic approach to examine the history of genes involved in cheating behaviors in the social amoeba Dictyostelium discoideum, testing whether these genes experience rapid evolutionary change as a result of conflict over spore-stalk fate. Candidate genes and surrounding regions showed elevated polymorphism, unusual patterns of linkage disequilibrium, and lower levels of population differentiation, but they did not show greater between-species divergence. The signatures were most consistent with frequency-dependent selection acting to maintain multiple alleles, suggesting that conflict may lead to stalemate rather than an escalating arms race. Our results reveal the evolutionary dynamics of cooperation and cheating and underscore how sequence-based approaches can be used to elucidate the history of conflicts that are difficult to observe directly.


Assuntos
Dictyostelium/genética , Genoma de Protozoário , Evolução Molecular , Genômica , Polimorfismo Genético , Seleção Genética
9.
Proc Natl Acad Sci U S A ; 110(36): 14528-33, 2013 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-23898207

RESUMO

Stable multipartite mutualistic associations require that all partners benefit. We show that a single mutational step is sufficient to turn a symbiotic bacterium from an inedible but host-beneficial secondary metabolite producer into a host food source. The bacteria's host is a "farmer" clone of the social amoeba Dictyostelium discoideum that carries and disperses bacteria during its spore stage. Associated with the farmer are two strains of Pseudomonas fluorescens, only one of which serves as a food source. The other strain produces diffusible small molecules: pyrrolnitrin, a known antifungal agent, and a chromene that potently enhances the farmer's spore production and depresses a nonfarmer's spore production. Genome sequence and phylogenetic analyses identify a derived point mutation in the food strain that generates a premature stop codon in a global activator (gacA), encoding the response regulator of a two-component regulatory system. Generation of a knockout mutant of this regulatory gene in the nonfood bacterial strain altered its secondary metabolite profile to match that of the food strain, and also, independently, converted it into a food source. These results suggest that a single mutation in an inedible ancestral strain that served a protective role converted it to a "domesticated" food source.


Assuntos
Proteínas de Bactérias/genética , Dictyostelium/fisiologia , Mutação , Pseudomonas fluorescens/genética , Sequência de Aminoácidos , Proteínas de Bactérias/metabolismo , Benzopiranos/química , Benzopiranos/metabolismo , Cromatografia Líquida de Alta Pressão , Códon sem Sentido , Dictyostelium/metabolismo , Dictyostelium/microbiologia , Genes Reguladores/genética , Interações Hospedeiro-Patógeno , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Estrutura Molecular , Filogenia , Pseudomonas fluorescens/classificação , Pseudomonas fluorescens/fisiologia , Pirrolnitrina/química , Pirrolnitrina/metabolismo , Homologia de Sequência de Aminoácidos , Esporos de Protozoários/metabolismo , Esporos de Protozoários/fisiologia
10.
Mol Biol Evol ; 30(4): 977-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23329689

RESUMO

von Baer's law states that early stages of animal development are the most conserved. More recent evidence supports a modified "hourglass" pattern in which an early but somewhat later stage is most conserved. Both patterns have been explained by the relative complexity of either temporal or spatial interactions; the greatest conservation and lowest evolvability occur at the time of the most complex interactions, because these cause larger effects that are harder for selection to alter. This general kind of explanation might apply universally across independent multicellular systems, as supported by the recent finding of the hourglass pattern in plants. We use RNA-seq expression data from the development of the slime mold Dictyostelium to demonstrate that it does not follow either of the two canonical patterns but instead tends to show the strongest conservation and weakest evolvability late in development. We propose that this is consistent with a version of the spatial constraints model, modified for organisms that never achieve a high degree of developmental modularity.


Assuntos
Dictyostelium/genética , Regulação da Expressão Gênica no Desenvolvimento , Animais , Evolução Biológica , Sequência Conservada , Dictyostelium/metabolismo , Dictyostelium/fisiologia , Expressão Gênica , Genes de Protozoários , Modelos Genéticos , Análise de Sequência de RNA
11.
PLoS One ; 7(9): e46150, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029418

RESUMO

Protein sequences are normally the most conserved elements of genomes owing to purifying selection to maintain their functions. We document an extraordinary amount of within-species protein sequence variation in the model eukaryote Dictyostelium discoideum stemming from triplet DNA repeats coding for long strings of single amino acids. D. discoideum has a very large number of such strings, many of which are polyglutamine repeats, the same sequence that causes various human neurological disorders in humans, like Huntington's disease. We show here that D. discoideum coding repeat loci are highly variable among individuals, making D. discoideum a candidate for the most variable proteome. The coding repeat loci are not significantly less variable than similar non-coding triplet repeats. This pattern is consistent with these amino-acid repeats being largely non-functional sequences evolving primarily by mutation and drift.


Assuntos
Dictyostelium/genética , Loci Gênicos , Genoma de Protozoário , Peptídeos/genética , Repetições de Trinucleotídeos , Motivos de Aminoácidos , Animais , Deriva Genética , Variação Genética , Humanos , Dados de Sequência Molecular , Mutação , Fases de Leitura Aberta , Filogenia
12.
Genome Biol ; 12(2): R20, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21356102

RESUMO

BACKGROUND: The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum. RESULTS: We have produced a draft genome sequence of another group dictyostelid, Dictyostelium purpureum, and compare it to the D. discoideum genome. The assembly (8.41 × coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict. CONCLUSIONS: The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.


Assuntos
Evolução Biológica , Dictyostelium/genética , Evolução Molecular , Genoma , Genômica/métodos , Animais , Sequência de Bases , Sequência Conservada/genética , Transferência Genética Horizontal , Especiação Genética , Tamanho do Genoma , Histidina Quinase , Humanos , Repetições de Microssatélites , Dados de Sequência Molecular , Filogenia , Policetídeo Sintases/genética , Proteínas Quinases/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie
13.
Mol Biol Evol ; 28(2): 899-909, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20943830

RESUMO

Simple sequence repeats (SSRs) or microsatellites are a common component of genomes but vary greatly across species in their abundance. We tested the hypothesis that this variation is due in part to AT/GC content of genomes, with genomes biased toward either high AT or high CG generating more short random repeats that are long enough to enhance expansion through slippage during replication. To test this hypothesis, we identified repeats with perfect tandem iterations of 1-6 bp from 25 protists with complete or near-complete genome sequences. As expected, the density and the frequency are highly related to genome AT content, with excellent fits to quadratic regressions with minima near a 50% AT content and rising toward both extremes. Within species, the same trends hold, except the limited variation in AT content within each species places each mainly on the descending (GC rich), middle, or ascending (AT rich) part of the curve. The base usages of repeat motifs are also significantly correlated with genome nucleotide compositions: Percentages of AT-rich motifs rise with the increase of genome AT content but vice versa for GC-rich subgroups. Amino acid homopolymer repeats also show the expected quadratic relationship, with higher abundance in species with AT content biased in either direction. Our results show that genome nucleotide composition explains up to half of the variance in the abundance and motif constitution of SSRs.


Assuntos
DNA de Protozoário/química , Eucariotos/genética , Genoma de Protozoário , Repetições de Microssatélites , Composição de Bases
14.
J Photochem Photobiol B ; 90(1): 17-25, 2008 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-18032059

RESUMO

In order to determine the role of laser in drought stress resistance of spring wheat (Triticum aestivum L.), seed embryos were exposed to CO2 laser radiation for 0min, 1min, 3min and 5min, respectively, and when the seedlings were 12 days old they were treated with 10% (w/v) PEG6000 solution for 10 days. Changes in the concentration of malondialdehyde (MDA), hydrogen peroxide (H2O2), glutathione (GSH), ascorbate (AsA), oxidized glutathione (GSSG), carotenoid, zeaxanthin, the production rate of superoxide radical (O2(-)), the activities of ascorbate peroxidase (APX), peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GP), glutathione-S-transferase (GST) and the growth parameters of seedlings (plant height, leaf area and dry weight) were measured to test the effects of laser pretreatment. The results showed that suitable laser pretreatment of embryos enhanced drought stress resistance in wheat seedlings by decreasing the concentration of MDA and H2O2, GSSG, the production rate of O2(-), leaf area and increasing the activities of APX, GST, GP and POD and AsA, carotenoid and zeaxanthin concentration. It is suggested that those changes in MDA, O2(-) H2O2, anti-oxidative enzymes and anti-oxidative compounds were responsible for the increase in drought stress resistance observed in the experiments. The results also showed that the laser had a long-term positive physiological effect on the growth of drought stress seedlings. This is the first investigation reporting the use of CO2 laser pretreatment to enhance drought stress resistance of spring wheat.


Assuntos
Dióxido de Carbono/farmacologia , Desastres , Lasers , Triticum/efeitos dos fármacos , Triticum/fisiologia , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Peróxidos/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Fatores de Tempo , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
15.
J Mol Evol ; 64(3): 299-307, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17273918

RESUMO

The transfer and integration of tRNA genes from organellar genomes to the nuclear genome and between organellar genomes occur extensively in flowering plants. The routes of the genetic materials flowing from one genome to another are biased, limited largely by compatibility of DNA replication and repair systems differing among the organelles and nucleus. After thoroughly surveying the tRNA gene transfer among organellar genomes and the nuclear genome of a domesticated rice (Oryza sativa L. ssp. indica), we found that (i) 15 mitochondrial tRNA genes originate from the plastid; (ii) 43 and 80 nuclear tRNA genes are mitochondrion-like and plastid-like, respectively; and (iii) 32 nuclear tRNA genes have both mitochondrial and plastid counterparts. Besides the native (or genuine) tRNA gene sets, the nuclear genome contains organelle-like tRNA genes that make up a complete set of tRNA species capable of transferring all amino acids. More than 97% of these organelle-like nuclear tRNA genes flank organelle-like sequences over 20 bp. Nearly 40% of them colocalize with two or more other organelle-like tRNA genes. Twelve of the 15 plastid-like mitochondrial tRNA genes possess 5'- and 3'-flanking sequences over 20 bp, and they are highly similar to their plastid counterparts. Phylogenetic analyses of the migrated tRNA genes and their original copies suggest that intergenomic tRNA gene transfer is an ongoing process with noticeable discriminatory routes among genomes in flowering plants.


Assuntos
Núcleo Celular/genética , Flores/genética , Mitocôndrias/genética , Oryza/genética , RNA de Transferência/genética , Recombinação Genética , Núcleo Celular/metabolismo , Evolução Molecular , Flores/metabolismo , Genes de Plantas/genética , Genoma de Planta , Mitocôndrias/metabolismo , Oryza/metabolismo , Filogenia , Plastídeos/genética , RNA de Transferência/metabolismo
16.
Int J Parasitol ; 36(9): 1049-56, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16797019

RESUMO

Microsporidia are a group of intracellular parasites with an extremely compact genome and there is no confirmed evidence that retroelements are parasitised in these organisms. Using the dataset of 200,000 genomic shotgun reads of the silkworm pebrine Nosema bombycis, we have identified the eight complete N. bombycis long-terminal repeat retrotransposon (Nbr) elements. All of the Nbr elements are Ty3/gypsy members and have close relationships to Saccharomycetes long-terminal repeat retrotransposons identified previously, providing further evidence of their relationship to fungi. To explore the effect of retrotransposons in microsporidian genome evolution, their distribution was characterised by comparisons between two N. bombycis contigs containing the Nbr elements with the completed genome of the human parasite Encephalitozoon cuniculi, which is closely related to N. bombycis. The Nbr elements locate between or beside syntenic blocks, which are often clustered with other transposable-like sequences, indicating that they are associated with genome size variation and syntenic discontinuities. The ratios of the number of non-synonymous substitutions per non-synonymous site to the number of synonymous substitutions per synonymous site of the open reading frames among members of each of the eight Nbr families were estimated, which reveal the purifying selection acted on the N. bombycis long-terminal repeat retrotransposons. These results strongly suggest that retrotransposons play a major role in reorganization of the microsporidian genome and they might be active. The present study presents an initial characterization of some transposable elements in the N. bombycis genome and provides some insight into the evolutionary mechanism of microsporidian genomes.


Assuntos
Bombyx/parasitologia , Nosema/genética , Retroelementos/genética , Sequências Repetidas Terminais , Sequência de Aminoácidos , Animais , Evolução Molecular , Genoma , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência
17.
Plant Physiol ; 140(2): 401-10, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16384910

RESUMO

Based on highly redundant and high-quality sequences, we assembled rice (Oryza sativa) mitochondrial genomes for two cultivars, 93-11 (an indica variety) and PA64S (an indica-like variety with maternal origin of japonica), which are paternal and maternal strains of an elite superhybrid rice Liang-You-Pei-Jiu (LYP-9), respectively. Following up with a previous analysis on rice chloroplast genomes, we divided mitochondrial sequence variations into two basic categories, intravarietal and intersubspecific. Intravarietal polymorphisms are variations within mitochondrial genomes of an individual variety. Intersubspecific polymorphisms are variations between subspecies among their major genotypes. In this study, we identified 96 single nucleotide polymorphisms (SNPs), 25 indels, and three segmental sequence variations as intersubspecific polymorphisms. A signature sequence fragment unique to indica varieties was confirmed experimentally and found in two wild rice samples, but absent in japonica varieties. The intersubspecific polymorphism rate for mitochondrial genomes is 0.02% for SNPs and 0.006% for indels, nearly 2.5 and 3 times lower than that of their chloroplast counterparts and 21 and 38 times lower than corresponding rates of the rice nuclear genome, respectively. The intravarietal polymorphism rates among analyzed mitochondrial genomes, such as 93-11 and PA64S, are 1.26% and 1.38% for SNPs and 1.13% and 1.09% for indels, respectively. Based on the total number of SNPs between the two mitochondrial genomes, we estimate that the divergence of indica and japonica mitochondrial genomes occurred approximately 45,000 to 250,000 years ago.


Assuntos
DNA Mitocondrial/genética , Variação Genética , Genoma de Planta , Mitocôndrias/genética , Oryza/genética , Sequência de Bases , Mapeamento Cromossômico , Genótipo , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Alinhamento de Sequência , Análise de Sequência de DNA
18.
Genomics Proteomics Bioinformatics ; 1(2): 101-7, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-15626340

RESUMO

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.


Assuntos
Variação Genética , Genoma Viral , Filogenia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/genética , Sequência de Bases , China , Análise por Conglomerados , Componentes do Gene , Genótipo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
19.
Genomics Proteomics Bioinformatics ; 1(2): 118-30, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-15626342

RESUMO

We studied structural and immunological properties of the SARS-CoV M (membrane) protein, based on comparative analyses of sequence features, phylogenetic investigation, and experimental results. The M protein is predicted to contain a triple-spanning transmembrane (TM) region, a single N-glycosylation site near its N-terminus that is in the exterior of the virion, and a long C-terminal region in the interior. The M protein harbors a higher substitution rate (0.6% correlated to its size) among viral open reading frames (ORFs) from published data. The four substitutions detected in the M protein, which cause non-synonymous changes, can be classified into three types. One of them results in changes of pI (isoelectric point) and charge, affecting antigenicity. The second changes hydrophobicity of the TM region, and the third one relates to hydrophilicity of the interior structure. Phylogenetic tree building based on the variations of the M protein appears to support the non-human origin of SARS-CoV. To investigate its immunogenicity, we synthesized eight oligopeptides covering 69.2% of the entire ORF and screened them by using ELISA (enzyme-linked immunosorbent assay) with sera from SARS patients. The results confirmed our predictions on antigenic sites.


Assuntos
Mutação/genética , Filogenia , Vírus da SARS/genética , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Sequência de Aminoácidos , Sequência de Bases , Análise por Conglomerados , Ensaio de Imunoadsorção Enzimática , Imunoensaio , Dados de Sequência Molecular , Oligopeptídeos , Estrutura Terciária de Proteína , Alinhamento de Sequência , Análise de Sequência de DNA , Proteínas da Matriz Viral/química
20.
Genomics Proteomics Bioinformatics ; 1(2): 145-54, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-15626344

RESUMO

The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with other viral structural proteins, the low variation rate of the N protein with regards to its size suggests its importance to the survival of the virus.


Assuntos
Antígenos Virais/imunologia , Variação Genética , Proteínas do Nucleocapsídeo/genética , Vírus da SARS/genética , Motivos de Aminoácidos/genética , Sequência de Aminoácidos , Composição de Bases , Sequência de Bases , Análise por Conglomerados , Biologia Computacional , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Nucleocapsídeo/metabolismo , Fosforilação , Análise de Sequência de DNA
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