Base de dados : MEDLINE
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  1 / 1985 MEDLINE  
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[PMID]:29326268
[Au] Autor:Cowell AN; Istvan ES; Lukens AK; Gomez-Lorenzo MG; Vanaerschot M; Sakata-Kato T; Flannery EL; Magistrado P; Owen E; Abraham M; LaMonte G; Painter HJ; Williams RM; Franco V; Linares M; Arriaga I; Bopp S; Corey VC; Gnädig NF; Coburn-Flynn O; Reimer C; Gupta P; Murithi JM; Moura PA; Fuchs O; Sasaki E; Kim SW; Teng CH; Wang LT; Akidil A; Adjalley S; Willis PA; Siegel D; Tanaseichuk O; Zhong Y; Zhou Y; Llinás M; Ottilie S; Gamo FJ; Lee MCS; Goldberg DE; Fidock DA; Wirth DF; Winzeler EA
[Ad] Endereço:School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92093, USA.
[Ti] Título:Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.
[So] Source:Science;359(6372):191-199, 2018 01 12.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Resistência a Medicamentos/genética
Genoma de Protozoário
Plasmodium falciparum/efeitos dos fármacos
Plasmodium falciparum/genética
[Mh] Termos MeSH secundário: Ativação Metabólica
Alelos
Variações do Número de Cópias de DNA
Evolução Molecular Direcionada
Resistência a Múltiplos Medicamentos/genética
Genes de Protozoários
Metabolômica
Mutação
Plasmodium falciparum/crescimento & desenvolvimento
Seleção Genética
Fatores de Transcrição/química
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1126/science.aan4472


  2 / 1985 MEDLINE  
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[PMID]:29304093
[Au] Autor:Schmid-Hempel P; Aebi M; Barribeau S; Kitajima T; du Plessis L; Schmid-Hempel R; Zoller S
[Ad] Endereço:Institute of Integrative Biology (IBZ), ETH Zurich, Zürich, Switzerland.
[Ti] Título:The genomes of Crithidia bombi and C. expoeki, common parasites of bumblebees.
[So] Source:PLoS One;13(1):e0189738, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trypanosomatids (Trypanosomatidae, Kinetoplastida) are flagellated protozoa containing many parasites of medical or agricultural importance. Among those, Crithidia bombi and C. expoeki, are common parasites in bumble bees around the world, and phylogenetically close to Leishmania and Leptomonas. They have a simple and direct life cycle with one host, and partially castrate the founding queens greatly reducing their fitness. Here, we report the nuclear genome sequences of one clone of each species, extracted from a field-collected infection. Using a combination of Roche 454 FLX Titanium, Pacific Biosciences PacBio RS, and Illumina GA2 instruments for C. bombi, and PacBio for C. expoeki, we could produce high-quality and well resolved sequences. We find that these genomes are around 32 and 34 MB, with 7,808 and 7,851 annotated genes for C. bombi and C. expoeki, respectively-which is somewhat less than reported from other trypanosomatids, with few introns, and organized in polycistronic units. A large fraction of genes received plausible functional support in comparison primarily with Leishmania and Trypanosoma. Comparing the annotated genes of the two species with those of six other trypanosomatids (C. fasciculata, L. pyrrhocoris, L. seymouri, B. ayalai, L. major, and T. brucei) shows similar gene repertoires and many orthologs. Similar to other trypanosomatids, we also find signs of concerted evolution in genes putatively involved in the interaction with the host, a high degree of synteny between C. bombi and C. expoeki, and considerable overlap with several other species in the set. A total of 86 orthologous gene groups show signatures of positive selection in the branch leading to the two Crithidia under study, mostly of unknown function. As an example, we examined the initiating glycosylation pathway of surface components in C. bombi, finding it deviates from most other eukaryotes and also from other kinetoplastids, which may indicate rapid evolution in the extracellular matrix that is involved in interactions with the host. Bumble bees are important pollinators and Crithidia-infections are suspected to cause substantial selection pressure on their host populations. These newly sequenced genomes provide tools that should help better understand host-parasite interactions in these pollinator pathogens.
[Mh] Termos MeSH primário: Abelhas/parasitologia
Crithidia/genética
Crithidia/patogenicidade
Genoma de Protozoário
[Mh] Termos MeSH secundário: Animais
Crithidia/classificação
Evolução Molecular
Interações Hospedeiro-Parasita/genética
Redes e Vias Metabólicas/genética
Anotação de Sequência Molecular
Filogenia
Polissacarídeos/metabolismo
Proteínas de Protozoários/genética
Especificidade da Espécie
Sintenia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Polysaccharides); 0 (Protozoan Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189738


  3 / 1985 MEDLINE  
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[PMID]:28454557
[Au] Autor:Cerqueira GC; Cheeseman IH; Schaffner SF; Nair S; McDew-White M; Phyo AP; Ashley EA; Melnikov A; Rogov P; Birren BW; Nosten F; Anderson TJC; Neafsey DE
[Ad] Endereço:Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
[Ti] Título:Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance.
[So] Source:Genome Biol;18(1):78, 2017 04 28.
[Is] ISSN:1474-760X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001-2014). RESULTS: We evaluate statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance increase in frequency over this period. After Kelch13-C580Y, the strongest temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is involved in a pathway recently implicated in artemisinin resistance. Furthermore, other loci exhibit strong temporal signatures which warrant further investigation for involvement in artemisinin resistance evolution. Through genome-wide association analysis we identify a variant in a kelch domain-containing gene on chromosome 10 that may epistatically modulate artemisinin resistance. CONCLUSIONS: This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated gene loci to improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of the kelch13 locus associated with artemisinin-resistant parasites may yield new molecular markers for resistance surveillance, which may be useful in efforts to reduce the emergence or spread of artemisinin resistance in African parasite populations.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Artemisininas/farmacologia
Resistência a Medicamentos/genética
Genoma de Protozoário
Plasmodium falciparum/genética
[Mh] Termos MeSH secundário: Repetição Kelch
Plasmodium falciparum/efeitos dos fármacos
Polimorfismo de Nucleotídeo Único
Proteínas de Protozoários/química
Proteínas de Protozoários/genética
Proteínas de Protozoários/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Protozoan Proteins); 9RMU91N5K2 (artemisinine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1186/s13059-017-1204-4


  4 / 1985 MEDLINE  
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[PMID]:29261763
[Au] Autor:Naves LL; da Silva MV; Fajardo EF; da Silva RB; De Vito FB; Rodrigues V; Lages-Silva E; Ramírez LE; Pedrosa AL
[Ad] Endereço:Departamento de Bioquímica, Farmacologia e Fisiologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brasil.
[Ti] Título:DNA content analysis allows discrimination between Trypanosoma cruzi and Trypanosoma rangeli.
[So] Source:PLoS One;12(12):e0189907, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trypanosoma cruzi, a human protozoan parasite, is the causative agent of Chagas disease. Currently the species is divided into six taxonomic groups. The genome of the CL Brener clone has been estimated to be 106.4-110.7 Mb, and DNA content analyses revealed that it is a diploid hybrid clone. Trypanosoma rangeli is a hemoflagellate that has the same reservoirs and vectors as T. cruzi; however, it is non-pathogenic to vertebrate hosts. The haploid genome of T. rangeli was previously estimated to be 24 Mb. The parasitic strains of T. rangeli are divided into KP1(+) and KP1(-). Thus, the objective of this study was to investigate the DNA content in different strains of T. cruzi and T. rangeli by flow cytometry. All T. cruzi and T. rangeli strains yielded cell cycle profiles with clearly identifiable G1-0 (2n) and G2-M (4n) peaks. T. cruzi and T. rangeli genome sizes were estimated using the clone CL Brener and the Leishmania major CC1 as reference cell lines because their genome sequences have been previously determined. The DNA content of T. cruzi strains ranged from 87,41 to 108,16 Mb, and the DNA content of T. rangeli strains ranged from 63,25 Mb to 68,66 Mb. No differences in DNA content were observed between KP1(+) and KP1(-) T. rangeli strains. Cultures containing mixtures of the epimastigote forms of T. cruzi and T. rangeli strains resulted in cell cycle profiles with distinct G1 peaks for strains of each species. These results demonstrate that DNA content analysis by flow cytometry is a reliable technique for discrimination between T. cruzi and T. rangeli isolated from different hosts.
[Mh] Termos MeSH primário: DNA de Protozoário/análise
Trypanosoma cruzi/genética
Trypanosoma rangeli/genética
[Mh] Termos MeSH secundário: Animais
Citometria de Fluxo
Genoma de Protozoário
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Protozoan)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189907


  5 / 1985 MEDLINE  
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[PMID]:28450531
[Au] Autor:Lindblad KA; Bracht JR; Williams AE; Landweber LF
[Ad] Endereço:Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
[Ti] Título:Thousands of RNA-cached copies of whole chromosomes are present in the ciliate during development.
[So] Source:RNA;23(8):1200-1208, 2017 08.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The ciliate maintains two genomes: a germline genome that is active only during sexual conjugation and a transcriptionally active, somatic genome that derives from the germline via extensive sequence reduction and rearrangement. Previously, we found that long noncoding (lnc) RNA "templates"-telomere-containing, RNA-cached copies of mature chromosomes-provide the information to program the rearrangement process. Here we used a modified RNA-seq approach to conduct the first genome-wide search for endogenous, telomere-to-telomere RNA transcripts. We find that during development, produces long noncoding RNA copies for over 10,000 of its 16,000 somatic chromosomes, consistent with a model in which transmits an RNA-cached copy of its somatic genome to the sexual progeny. Both the primary sequence and expression profile of a somatic chromosome influence the temporal distribution and abundance of individual template RNAs. This suggests that may undergo multiple rounds of DNA rearrangement during development. These observations implicate a complex set of thousands of long RNA molecules in the wiring and maintenance of a highly elaborate somatic genome architecture.
[Mh] Termos MeSH primário: Cromossomos/genética
Genoma de Protozoário/genética
Oxytricha/genética
RNA Longo não Codificante/genética
RNA de Protozoário/genética
[Mh] Termos MeSH secundário: Animais
Variações do Número de Cópias de DNA
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Oxytricha/crescimento & desenvolvimento
Telômero/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (RNA, Long Noncoding); 0 (RNA, Protozoan)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171223
[Lr] Data última revisão:
171223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1261/rna.058511.116


  6 / 1985 MEDLINE  
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[PMID]:28742144
[Au] Autor:Stortz JA; Serafim TD; Alsford S; Wilkes J; Fernandez-Cortes F; Hamilton G; Briggs E; Lemgruber L; Horn D; Mottram JC; McCulloch R
[Ad] Endereço:The Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
[Ti] Título:Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei.
[So] Source:PLoS Pathog;13(7):e1006477, 2017 Jul.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:All cells are subject to structural damage that must be addressed for continued growth. A wide range of damage affects the genome, meaning multiple pathways have evolved to repair or bypass the resulting DNA lesions. Though many repair pathways are conserved, their presence or function can reflect the life style of individual organisms. To identify genome maintenance pathways in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens to identify genes important for survival following exposure to the alkylating agent methyl methanesulphonate. Amongst a cohort of broadly conserved and, therefore, early evolved repair pathways, we reveal multiple activities not so far examined functionally in T. brucei, including DNA polymerases, DNA helicases and chromatin factors. In addition, the screens reveal Trypanosoma- or kinetoplastid-specific repair-associated activities. We also provide focused analyses of repair-associated protein kinases and show that loss of at least nine, and potentially as many as 30 protein kinases, including a nuclear aurora kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the potential for synthetic lethal genome-wide screening of gene function in T. brucei and provide an evolutionary perspective on the repair pathways that underpin effective responses to damage, with particular relevance for related kinetoplastid pathogens. By revealing that a large number of diverse T. brucei protein kinases act in the response to damage, we expand the range of eukaryotic signalling factors implicated in genome maintenance activities.
[Mh] Termos MeSH primário: Reparo do DNA
Genoma de Protozoário
Proteínas Quinases/genética
Proteínas de Protozoários/genética
Interferência de RNA
Trypanosoma brucei brucei/enzimologia
Trypanosoma brucei brucei/genética
[Mh] Termos MeSH secundário: Dano ao DNA/efeitos dos fármacos
Evolução Molecular
Metanossulfonato de Metila/análogos & derivados
Metanossulfonato de Metila/toxicidade
Mutagênicos/toxicidade
Proteínas Quinases/metabolismo
Proteínas de Protozoários/metabolismo
Trypanosoma brucei brucei/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Protozoan Proteins); 2949-92-0 (methyl methanethiosulfonate); AT5C31J09G (Methyl Methanesulfonate); EC 2.7.- (Protein Kinases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171213
[Lr] Data última revisão:
171213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006477


  7 / 1985 MEDLINE  
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[PMID]:28961244
[Au] Autor:Durante IM; La Spina PE; Carmona SJ; Agüero F; Buscaglia CA
[Ad] Endereço:Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECh), Universidad Nacional de San Martín (UNSAM) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Buenos Aires, Argentina.
[Ti] Título:High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of Trypanosoma cruzi during human infections.
[So] Source:PLoS Negl Trop Dis;11(9):e0005986, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The Trypanosoma cruzi genome bears a huge family of genes and pseudogenes coding for Mucin-Associated Surface Proteins (MASPs). MASP molecules display a 'mosaic' structure, with highly conserved flanking regions and a strikingly variable central and mature domain made up of different combinations of a large repertoire of short sequence motifs. MASP molecules are highly expressed in mammal-dwelling stages of T. cruzi and may be involved in parasite-host interactions and/or in diverting the immune response. METHODS/PRINCIPLE FINDINGS: High-density microarrays composed of fully overlapped 15mer peptides spanning the entire sequences of 232 non-redundant MASPs (~25% of the total MASP content) were screened with chronic Chagasic sera. This strategy led to the identification of 86 antigenic motifs, each one likely representing a single linear B-cell epitope, which were mapped to 69 different MASPs. These motifs could be further grouped into 31 clusters of structurally- and likely antigenically-related sequences, and fully characterized. In contrast to previous reports, we show that MASP antigenic motifs are restricted to the central and mature region of MASP polypeptides, consistent with their intracellular processing. The antigenicity of these motifs displayed significant positive correlation with their genome dosage and their relative position within the MASP polypeptide. In addition, we verified the biased genetic co-occurrence of certain antigenic motifs within MASP polypeptides, compatible with proposed intra-family recombination events underlying the evolution of their coding genes. Sequences spanning 7 MASP antigenic motifs were further evaluated using distinct synthesis/display approaches and a large panel of serum samples. Overall, the serological recognition of MASP antigenic motifs exhibited a remarkable non normal distribution among the T. cruzi seropositive population, thus reducing their applicability in conventional serodiagnosis. As previously observed in in vitro and animal infection models, immune signatures supported the concurrent expression of several MASPs during human infection. CONCLUSIONS/SIGNIFICANCE: In spite of their conspicuous expression and potential roles in parasite biology, this study constitutes the first unbiased, high-resolution profiling of linear B-cell epitopes from T. cruzi MASPs during human infection.
[Mh] Termos MeSH primário: Antígenos de Protozoários
Doença de Chagas/parasitologia
Epitopos de Linfócito B/química
Genoma de Protozoário
Proteínas de Membrana/imunologia
Trypanosoma cruzi/genética
Trypanosoma cruzi/imunologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Antígenos de Protozoários/química
Antígenos de Protozoários/genética
Epitopos de Linfócito B/genética
Epitopos de Linfócito B/imunologia
Seres Humanos
Soros Imunes
Proteínas de Membrana/química
Proteínas de Membrana/genética
Mucinas/química
Análise Serial de Proteínas
Proteínas de Protozoários/química
Proteínas de Protozoários/genética
Proteínas de Protozoários/imunologia
Trypanosoma cruzi/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Epitopes, B-Lymphocyte); 0 (Immune Sera); 0 (Membrane Proteins); 0 (Mucins); 0 (Protozoan Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005986


  8 / 1985 MEDLINE  
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[PMID]:28961238
[Au] Autor:Richardson JB; Lee KY; Mireji P; Enyaru J; Sistrom M; Aksoy S; Zhao H; Caccone A
[Ad] Endereço:Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, United States of America.
[Ti] Título:Genomic analyses of African Trypanozoon strains to assess evolutionary relationships and identify markers for strain identification.
[So] Source:PLoS Negl Trop Dis;11(9):e0005949, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:African trypanosomes of the sub-genus Trypanozoon) are eukaryotic parasitesthat cause disease in either humans or livestock. The development of genomic resources can be of great use to those interested in studying and controlling the spread of these trypanosomes. Here we present a large comparative analysis of Trypanozoon whole genomes, 83 in total, including human and animal infective African trypanosomes: 21 T. brucei brucei, 22 T. b. gambiense, 35 T. b. rhodesiense and 4 T. evansi strains, of which 21 were from Uganda. We constructed a maximum likelihood phylogeny based on 162,210 single nucleotide polymorphisms (SNPs.) The three Trypanosoma brucei sub-species and Trypanosoma evansi are not monophyletic, confirming earlier studies that indicated high similarity among Trypanosoma "sub-species". We also used discriminant analysis of principal components (DAPC) on the same set of SNPs, identifying seven genetic clusters. These clusters do not correspond well with existing taxonomic classifications, in agreement with the phylogenetic analysis. Geographic origin is reflected in both the phylogeny and clustering analysis. Finally, we used sparse linear discriminant analysis to rank SNPs by their informativeness in differentiating the strains in our data set. As few as 84 SNPs can completely distinguish the strains used in our study, and discriminant analysis was still able to detect genetic structure using as few as 10 SNPs. Our results reinforce earlier results of high genetic similarity between the African Trypanozoon. Despite this, a small subset of SNPs can be used to identify genetic markers that can be used for strain identification or other epidemiological investigations.
[Mh] Termos MeSH primário: Evolução Molecular
Genoma de Protozoário
Trypanosoma/classificação
Trypanosoma/genética
[Mh] Termos MeSH secundário: Motivos de Aminoácidos/genética
Marcadores Genéticos
Família Multigênica
Filogenia
Polimorfismo de Nucleotídeo Único
Trypanosoma/isolamento & purificação
Trypanosoma brucei brucei/genética
Trypanosoma brucei gambiense/genética
Trypanosoma brucei rhodesiense/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005949


  9 / 1985 MEDLINE  
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[PMID]:28892507
[Au] Autor:Gentekaki E; Curtis BA; Stairs CW; Klimes V; Eliás M; Salas-Leiva DE; Herman EK; Eme L; Arias MC; Henrissat B; Hilliou F; Klute MJ; Suga H; Malik SB; Pightling AW; Kolisko M; Rachubinski RA; Schlacht A; Soanes DM; Tsaousis AD; Archibald JM; Ball SG; Dacks JB; Clark CG; van der Giezen M; Roger AJ
[Ad] Endereço:Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
[Ti] Título:Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis.
[So] Source:PLoS Biol;15(9):e2003769, 2017 Sep.
[Is] ISSN:1545-7885
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%-61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize α-glucans rather than ß-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease.
[Mh] Termos MeSH primário: Blastocystis/genética
Genoma de Protozoário
[Mh] Termos MeSH secundário: Blastocystis/metabolismo
Metabolismo dos Carboidratos
Códon de Terminação
Microbioma Gastrointestinal
Seres Humanos
Íntrons
Especificidade da Espécie
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Terminator)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pbio.2003769


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[PMID]:28708996
[Au] Autor:Bushell E; Gomes AR; Sanderson T; Anar B; Girling G; Herd C; Metcalf T; Modrzynska K; Schwach F; Martin RE; Mather MW; McFadden GI; Parts L; Rutledge GG; Vaidya AB; Wengelnik K; Rayner JC; Billker O
[Ad] Endereço:Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
[Ti] Título:Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes.
[So] Source:Cell;170(2):260-272.e8, 2017 Jul 13.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of Plasmodium parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.
[Mh] Termos MeSH primário: Genoma de Protozoário
Plasmodium berghei/crescimento & desenvolvimento
Plasmodium berghei/genética
[Mh] Termos MeSH secundário: Animais
Evolução Biológica
Feminino
Técnicas de Inativação de Genes
Genes Essenciais
Interações Hospedeiro-Parasita
Redes e Vias Metabólicas
Camundongos
Camundongos Endogâmicos BALB C
Plasmodium berghei/metabolismo
Saccharomyces cerevisiae/genética
Toxoplasma/genética
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE



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