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1.
Viruses ; 12(9)2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937868

RESUMO

BACKGROUND: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. METHODS: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. RESULTS: We identified 14 variant sites ≥5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 × 10-3 substitutions per year. CONCLUSIONS: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/virologia , Mutação , Pandemias , Pneumonia Viral/virologia , Adulto , Idoso , Teorema de Bayes , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Conjuntos de Dados como Assunto , Evolução Molecular , Feminino , Variação Genética , Genoma Viral , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , RNA Viral/genética , Recombinação Genética , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Suécia/epidemiologia
2.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 380-383, 2020 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-32935512

RESUMO

OBJECTIVE: To investigate the genetic variation of Eurytrema pancreaticum isolated from goats in Huaihua City, Hunan Province. METHODS: The partial sequence of mitochondrial cytochrome I (pcox1) and ribosomal 18S rRNA genes were amplified using a PCR assay in E. pancreaticum isolates from goats in Huaihua City, Hunan Province, and the PCR amplification products were sequenced. Then, the gene sequences were subjected to genetic variation and phylogenetic analyses. RESULTS: The sequences of the pcox1 and 18S rRNA genes were 430 bp and 1 857 bp in length in 18 E. pancreaticum isolates from goats in Huaihua City, Hunan Province, and there were 14 and 35 variation sites in pcox1 and 18S rRNA gene sequences, with intra-species genetic variations of 0 to 1.4% and 0 to 0.8%, respectively. The sequences of pcox1 and 18S rRNA genes had 99.0% to 99.8% and 99.5% to 99.8% homologies with those from E. pancreaticum Chinese strain recorded in the GenBank database. Consistent phylogenetic analysis results were found based on pcox1 and 18S rRNA genes. The 18 E. pancreaticum isolates from goats in Huaihua City were clustered into a clade with the known E. pancreaticum isolates registered in GenBank, and the clade with these 18 E. pancreaticum isolates was close to the clades with Eurytrema species and far from the clades with other trematodes. CONCLUSIONS: The E. pancreaticum isolates from goats have a low genetic variation in Huaihua City, Hunan Province. Mitochondrial pcox1 and ribosomal 18S rRNA genes may serve as molecular markers for the studies on the genetic variation in goat-derived E. pancreaticum.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons , Variação Genética , Cabras , RNA Ribossômico 18S , Trematódeos , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Cabras/parasitologia , Filogenia , RNA Ribossômico 18S/genética , Homologia de Sequência do Ácido Nucleico , Trematódeos/classificação , Trematódeos/genética , Trematódeos/isolamento & purificação
3.
Genome Res ; 30(10): 1434-1448, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32878977

RESUMO

The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extent.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Genoma Viral/genética , Pneumonia Viral/epidemiologia , Animais , Ásia/epidemiologia , Sequência de Bases/genética , Quirópteros/virologia , Mapeamento Cromossômico , Europa (Continente)/epidemiologia , Evolução Molecular , Variação Genética/genética , Humanos , Pandemias , Filogenia , Filogeografia , Homologia de Sequência do Ácido Nucleico
4.
Nat Commun ; 11(1): 3328, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620864

RESUMO

Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutations cause pathology. Here we introduce a strategy to define complete portfolios of full-length isoforms encoded by individual genes. Applying this approach to neural cell-surface molecules, we identify thousands of unannotated isoforms expressed in retina and brain. By mass spectrometry we confirm expression of newly-discovered proteins on the cell surface in vivo. Remarkably, we discover that the major isoform of a retinal degeneration gene, CRB1, was previously overlooked. This CRB1 isoform is the only one expressed by photoreceptors, the affected cells in CRB1 disease. Using mouse mutants, we identify a function for this isoform at photoreceptor-glial junctions and demonstrate that loss of this isoform accelerates photoreceptor death. Therefore, our isoform identification strategy enables discovery of new gene functions relevant to disease.


Assuntos
Variação Genética , Proteínas de Membrana/genética , Células Fotorreceptoras de Vertebrados/metabolismo , Isoformas de RNA/genética , Retina/metabolismo , Degeneração Retiniana/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Isoformas de RNA/metabolismo , Retina/citologia , Retina/crescimento & desenvolvimento , Degeneração Retiniana/metabolismo , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico
5.
Mol Cell ; 79(3): 416-424.e5, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32645367

RESUMO

CRISPR-Cas12c/d proteins share limited homology with Cas12a and Cas9 bacterial CRISPR RNA (crRNA)-guided nucleases used widely for genome editing and DNA detection. However, Cas12c (C2c3)- and Cas12d (CasY)-catalyzed DNA cleavage and genome editing activities have not been directly observed. We show here that a short-complementarity untranslated RNA (scoutRNA), together with crRNA, is required for Cas12d-catalyzed DNA cutting. The scoutRNA differs in secondary structure from previously described tracrRNAs used by CRISPR-Cas9 and some Cas12 enzymes, and in Cas12d-containing systems, scoutRNA includes a conserved five-nucleotide sequence that is essential for activity. In addition to supporting crRNA-directed DNA recognition, biochemical and cell-based experiments establish scoutRNA as an essential cofactor for Cas12c-catalyzed pre-crRNA maturation. These results define scoutRNA as a third type of transcript encoded by a subset of CRISPR-Cas genomic loci and explain how Cas12c/d systems avoid requirements for host factors including ribonuclease III for bacterial RNA-mediated adaptive immunity.


Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Endodesoxirribonucleases/genética , Genoma Bacteriano/imunologia , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Bactérias/classificação , Bactérias/imunologia , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Sequência de Bases , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Endodesoxirribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/imunologia , Escherichia coli/metabolismo , Conformação de Ácido Nucleico , Filogenia , RNA Bacteriano/química , RNA Bacteriano/metabolismo , RNA Guia/genética , RNA Guia/metabolismo , Pequeno RNA não Traduzido/química , Pequeno RNA não Traduzido/metabolismo , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
6.
In Vivo ; 34(3 Suppl): 1633-1636, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-534631

RESUMO

In a previous study, we identified a 117 base severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 Orf1b gene in non-structural protein 14 (NSP14), which is an exonuclease and NSP15, an endoribonuclease. In the current study we compared the human genome with other viral genomes to determine some of the characteristics of human sequences found in the latter. Most of the viruses had human sequences, but they were short. Hepatitis A and St Louis encephalitis had human sequences that were longer than the 117 base SARS-Cov-2 sequence, but they were in non-coding regions of the human genome. The SARS-Cov-2 sequence was the only long sequence found in a human gene (NTNG1). The related coronaviruses SARS-Cov had a 41 BP human sequence on chromosome 3 that was not part of a human gene, and MERS had no human sequence. The 117 base SARS-CoV-2 human sequence is relatively close to the viral spike sequence, separated only by NSP16, a 904 base sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. We have no explanation for the NSP14 and NSP15 SARS-Cov-2 sequences we observed here or how they might relate to infectiousness. Further studies are warranted.


Assuntos
Betacoronavirus/genética , Genoma Viral , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 3/genética , Vírus de DNA/genética , Endorribonucleases/genética , Proteínas Ligadas por GPI/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Netrinas/genética , Vírus de RNA/genética , Vírus da SARS/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética
7.
In Vivo ; 34(3 Suppl): 1629-1632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-534630

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In the current analysis, we searched for SARS-CoV-2 sequences within the human genome. To compare the SARS-CoV-2 genome to the human genome, we used the blast-like alignment tool (BLAT) of the University of California, Santa Cruz Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. BLAT search results revealed a 117-base pair SARS-CoV-2 sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 orf1b (open reading frames) gene. The SARS-CoV-2 human sequence lies within non-structural proteins 14 and 15 (NSP14 and NSP15), and is quite close to the viral spike sequence, separated only by NSP16, a 904-base pair sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 and internalization of the complex by the host cell. It is probably no accident that a sequence from the SARS-CoV-2 orf1b gene is found in the human NTNG1 gene, implicated in schizophrenia, and that haloperidol, used to treat schizophrenia, may also be a treatment for COVID-19. We suggest, therefore, that it is important to investigate other haloperidol analogs. Among them are benperidol, bromperidol, bromperidol decanoate, droperidol, seperidol hydrochloride, and trifluperidol. These analogs might be valuable in the treatment of COVID-19 and other coronavirus infections.


Assuntos
Betacoronavirus/genética , Cromossomos Humanos Par 1/genética , Genes Virais , Netrina-1/genética , Proteínas Virais/genética , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Sequência de Bases , Infecções por Coronavirus/tratamento farmacológico , DNA Complementar/genética , Endorribonucleases/genética , Exorribonucleases/genética , Haloperidol/análogos & derivados , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Humanos , Íntrons/genética , Pan troglodytes/genética , Pandemias , Pneumonia Viral/tratamento farmacológico , RNA Viral/genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Proteínas não Estruturais Virais/genética
8.
PLoS One ; 15(6): e0234272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502196

RESUMO

Insects have long been thought to largely not require hemoglobins, with some notable exceptions like the red hemolymph of chironomid larvae. The tubular, branching network of tracheae in hexapods is traditionally considered sufficient for their respiration. Where hemoglobins do occur sporadically in plants and animals, they are believed to be either convergent, or because they are ancient in origin and their expression is lost in many clades. Our comprehensive analysis of 845 Hexapod transcriptomes, totaling over 38 Gbases, revealed the expression of hemoglobins in all 32 orders of hexapods, including the 29 recognized orders of insects. Discovery and identification of 1333 putative hemoglobins were achieved with target-gene BLAST searches of the NCBI TSA database, verifying functional residues, secondary- and tertiary-structure predictions, and localization predictions based on machine learning. While the majority of these hemoglobins are intracellular, extracellular ones were recovered in 38 species. Gene trees were constructed via multiple-sequence alignments and phylogenetic analyses. These indicate duplication events within insects and a monophyletic grouping of hemoglobins outside other globin clades, for which we propose the term insectahemoglobins. These hemoglobins are phylogenetically adjacent and appear structurally convergent with the clade of chordate myoglobins, cytoglobins, and hemoglobins. Their derivation and co-option from early neuroglobins may explain the widespread nature of hemoglobins in various kingdoms and phyla. These results will guide future work involving genome comparisons to transcriptome results, experimental investigations of gene expression, cell and tissue localization, and gas binding properties, all of which are needed to further illuminate the complex respiratory adaptations in insects.


Assuntos
Artrópodes/genética , Perfilação da Expressão Gênica , Hemoglobinas/genética , Sequência de Aminoácidos , Animais , Hemoglobinas/química , Homologia de Sequência do Ácido Nucleico
9.
Nat Commun ; 11(1): 2885, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514036

RESUMO

The number of male gametes is critical for reproductive success and varies between and within species. The evolutionary reduction of the number of pollen grains encompassing the male gametes is widespread in selfing plants. Here, we employ genome-wide association study (GWAS) to identify underlying loci and to assess the molecular signatures of selection on pollen number-associated loci in the predominantly selfing plant Arabidopsis thaliana. Regions of strong association with pollen number are enriched for signatures of selection, indicating polygenic selection. We isolate the gene REDUCED POLLEN NUMBER1 (RDP1) at the locus with the strongest association. We validate its effect using a quantitative complementation test with CRISPR/Cas9-generated null mutants in nonstandard wild accessions. In contrast to pleiotropic null mutants, only pollen numbers are significantly affected by natural allelic variants. These data support theoretical predictions that reduced investment in male gametes is advantageous in predominantly selfing species.


Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Genes de Plantas/genética , Pólen/genética , Arabidopsis/metabolismo , Sequência de Bases , Sistemas CRISPR-Cas/genética , Evolução Molecular , Mutação , Plantas Geneticamente Modificadas , Pólen/citologia , Pólen/metabolismo , Reprodução/genética , Homologia de Sequência do Ácido Nucleico
10.
In Vivo ; 34(3 Suppl): 1629-1632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503821

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In the current analysis, we searched for SARS-CoV-2 sequences within the human genome. To compare the SARS-CoV-2 genome to the human genome, we used the blast-like alignment tool (BLAT) of the University of California, Santa Cruz Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. BLAT search results revealed a 117-base pair SARS-CoV-2 sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 orf1b (open reading frames) gene. The SARS-CoV-2 human sequence lies within non-structural proteins 14 and 15 (NSP14 and NSP15), and is quite close to the viral spike sequence, separated only by NSP16, a 904-base pair sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 and internalization of the complex by the host cell. It is probably no accident that a sequence from the SARS-CoV-2 orf1b gene is found in the human NTNG1 gene, implicated in schizophrenia, and that haloperidol, used to treat schizophrenia, may also be a treatment for COVID-19. We suggest, therefore, that it is important to investigate other haloperidol analogs. Among them are benperidol, bromperidol, bromperidol decanoate, droperidol, seperidol hydrochloride, and trifluperidol. These analogs might be valuable in the treatment of COVID-19 and other coronavirus infections.


Assuntos
Betacoronavirus/genética , Cromossomos Humanos Par 1/genética , Exorribonucleases/genética , Genes Virais , Netrina-1/genética , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Sequência de Bases , Infecções por Coronavirus/tratamento farmacológico , DNA Complementar/genética , Endorribonucleases/genética , Haloperidol/análogos & derivados , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Humanos , Íntrons/genética , Pan troglodytes/genética , Pandemias , Pneumonia Viral/tratamento farmacológico , RNA Viral/genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie
11.
In Vivo ; 34(3 Suppl): 1633-1636, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503822

RESUMO

In a previous study, we identified a 117 base severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 Orf1b gene in non-structural protein 14 (NSP14), which is an exonuclease and NSP15, an endoribonuclease. In the current study we compared the human genome with other viral genomes to determine some of the characteristics of human sequences found in the latter. Most of the viruses had human sequences, but they were short. Hepatitis A and St Louis encephalitis had human sequences that were longer than the 117 base SARS-Cov-2 sequence, but they were in non-coding regions of the human genome. The SARS-Cov-2 sequence was the only long sequence found in a human gene (NTNG1). The related coronaviruses SARS-Cov had a 41 BP human sequence on chromosome 3 that was not part of a human gene, and MERS had no human sequence. The 117 base SARS-CoV-2 human sequence is relatively close to the viral spike sequence, separated only by NSP16, a 904 base sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. We have no explanation for the NSP14 and NSP15 SARS-Cov-2 sequences we observed here or how they might relate to infectiousness. Further studies are warranted.


Assuntos
Betacoronavirus/genética , Exorribonucleases/genética , Genoma Viral , Vírus da SARS/genética , Proteínas não Estruturais Virais/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 3/genética , Vírus de DNA/genética , Proteínas Ligadas por GPI/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Netrinas/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Proteínas Virais/genética
12.
PLoS Pathog ; 16(5): e1008421, 2020 05.
Artigo em Inglês | MEDLINE | ID: covidwho-260623

RESUMO

The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.


Assuntos
Betacoronavirus/classificação , Betacoronavirus/genética , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Eutérios/virologia , Pneumonia Viral/virologia , Animais , Coronaviridae/classificação , Coronaviridae/genética , Especificidade de Hospedeiro , Humanos , Pandemias , Filogenia , Homologia de Sequência do Ácido Nucleico , Zoonoses/prevenção & controle , Zoonoses/virologia
13.
PLoS Biol ; 18(5): e3000627, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32421706

RESUMO

Despite over a billion years of evolutionary divergence, several thousand human genes possess clearly identifiable orthologs in yeast, and many have undergone lineage-specific duplications in one or both lineages. These duplicated genes may have been free to diverge in function since their expansion, and it is unclear how or at what rate ancestral functions are retained or partitioned among co-orthologs between species and within gene families. Thus, in order to investigate how ancestral functions are retained or lost post-duplication, we systematically replaced hundreds of essential yeast genes with their human orthologs from gene families that have undergone lineage-specific duplications, including those with single duplications (1 yeast gene to 2 human genes, 1:2) or higher-order expansions (1:>2) in the human lineage. We observe a variable pattern of replaceability across different ortholog classes, with an obvious trend toward differential replaceability inside gene families, and rarely observe replaceability by all members of a family. We quantify the ability of various properties of the orthologs to predict replaceability, showing that in the case of 1:2 orthologs, replaceability is predicted largely by the divergence and tissue-specific expression of the human co-orthologs, i.e., the human proteins that are less diverged from their yeast counterpart and more ubiquitously expressed across human tissues more often replace their single yeast ortholog. These trends were consistent with in silico simulations demonstrating that when only one ortholog can replace its corresponding yeast equivalent, it tends to be the least diverged of the pair. Replaceability of yeast genes having more than 2 human co-orthologs was marked by retention of orthologous interactions in functional or protein networks as well as by more ancestral subcellular localization. Overall, we performed >400 human gene replaceability assays, revealing 50 new human-yeast complementation pairs, thus opening up avenues to further functionally characterize these human genes in a simplified organismal context.


Assuntos
Evolução Molecular , Genes Duplicados , Genes Fúngicos , Família Multigênica , Saccharomycetales/genética , Expressão Gênica , Teste de Complementação Genética , Humanos , Homologia de Sequência do Ácido Nucleico
14.
PLoS Pathog ; 16(5): e1008421, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32407364

RESUMO

The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.


Assuntos
Betacoronavirus/classificação , Betacoronavirus/genética , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Eutérios/virologia , Pneumonia Viral/virologia , Animais , Coronaviridae/classificação , Coronaviridae/genética , Especificidade de Hospedeiro , Humanos , Pandemias , Filogenia , Homologia de Sequência do Ácido Nucleico , Zoonoses/prevenção & controle , Zoonoses/virologia
15.
Med Sci (Paris) ; 36(4): 421-423, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32356723

RESUMO

Sophisticated analyses of current human populations compared to a high-coverage Neandertal genome sequence indicate that, contrary to the previous consensus, African genomes carry a small but significant amount of Neandertal-specific DNA. This indicates back-migration into Africa of modern humans (carrying some Neandertal sequences) and underlines the complexity of ancient human migrations.


Assuntos
DNA/genética , Hominidae/genética , Homem de Neandertal/genética , África , Animais , DNA/análise , Evolução Molecular , Genética Populacional , Genoma , História do Século XXI , História Antiga , Hominidae/classificação , Humanos , Hibridização Genética , Homem de Neandertal/classificação , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
16.
Nature ; 583(7815): 286-289, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380510

RESUMO

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.


Assuntos
Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Eutérios/virologia , Evolução Molecular , Genoma Viral/genética , Homologia de Sequência do Ácido Nucleico , Animais , Betacoronavirus/classificação , China , Quirópteros/virologia , Chlorocebus aethiops , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Genômica , Especificidade de Hospedeiro , Humanos , Pulmão/patologia , Pulmão/virologia , Malásia , Proteínas do Nucleocapsídeo/genética , Pandemias , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , Recombinação Genética , Alinhamento de Sequência , Análise de Sequência de RNA , Glicoproteína da Espícula de Coronavírus/genética , Células Vero , Proteínas do Envelope Viral/genética , Proteínas da Matriz Viral/genética , Zoonoses/transmissão , Zoonoses/virologia
17.
Infect Genet Evol ; 82: 104285, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-6174

RESUMO

The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.


Assuntos
Betacoronavirus/genética , Coronavirus/genética , Evolução Molecular , Animais , Betacoronavirus/classificação , Quirópteros/virologia , Coronavirus/classificação , Coronavirus/isolamento & purificação , Mamíferos/classificação , Mamíferos/virologia , Mutação , Filogenia , RNA Viral , Homologia de Sequência do Ácido Nucleico
18.
J Med Virol ; 92(6): 660-666, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32159237

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA-dependent RNA polymerase and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over-biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.


Assuntos
Betacoronavirus/genética , Cisteína Endopeptidases/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Proteínas do Nucleocapsídeo/genética , RNA Replicase/genética , Vírus da SARS/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética , Animais , Sequência de Bases , Betacoronavirus/classificação , Betacoronavirus/patogenicidade , Quirópteros/microbiologia , Uso do Códon , Biologia Computacional , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/metabolismo , Eutérios/microbiologia , Expressão Gênica , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Proteínas do Nucleocapsídeo/metabolismo , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , RNA Replicase/metabolismo , Vírus da SARS/classificação , Vírus da SARS/patogenicidade , Homologia de Sequência do Ácido Nucleico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Proteínas do Envelope Viral/metabolismo , Proteínas não Estruturais Virais/metabolismo
19.
J Med Virol ; 92(6): 667-674, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167180

RESUMO

Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Genoma Viral , Taxa de Mutação , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sequência de Bases , Betacoronavirus/classificação , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Bases de Dados Genéticas , Humanos , Fases de Leitura Aberta , Filogenia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , RNA Viral/genética , Padrões de Referência , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
20.
Arch Virol ; 165(5): 1225-1229, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32146505

RESUMO

Using a high-throughput sequencing approach, we identified four genomoviruses (family Genomoviridae) associated with a sweet orange (Citrus sinensis) plant collected in Tunisia. The ssDNA genomes of these genomoviruses, which were amplified, cloned and Sanger sequenced, range in size from 2156 to 2191 nt. Three of these viruses share > 99% full-genome pairwise sequence identity and are referred to as citrus Tunisia genomovirus 1 (CTNGmV-1). The CTNGmV-1 isolates share < 62% genome-wide pairwise nucleotide sequence identity with other genomoviruses and belong to the genus Gemykolovirus. The genome of the fourth virus, which was called CTNGmV-2, shares < 68% nucleotide sequence identity with other genomoviruses and belongs to the genus Gemycircularvirus. Based on the species demarcation criteria for members of the family Genomoviridae, CTNGmV-1 and -2 would each represent a new species. Although found associated with Citrus sp. plants, it is likely that these viruses infect fungi or other organisms associated with the plants.


Assuntos
Citrus/virologia , Vírus de DNA/classificação , Vírus de DNA/isolamento & purificação , Micovírus/classificação , Micovírus/isolamento & purificação , Análise de Sequência de DNA , Vírus de DNA/genética , Micovírus/genética , Filogenia , Vírus de Plantas/classificação , Vírus de Plantas/genética , Vírus de Plantas/isolamento & purificação , Homologia de Sequência do Ácido Nucleico , Tunísia
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