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1.
Viruses ; 13(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209881

RESUMO

The viral family Coronaviridae comprises four genera, termed Alpha-, Beta-, Gamma-, and Deltacoronavirus. Recombination events have been described in many coronaviruses infecting humans and other animals. However, formal analysis of the recombination patterns, both in terms of the involved genome regions and the extent of genetic divergence between partners, are scarce. Common methods of recombination detection based on phylogenetic incongruences (e.g., a phylogenetic compatibility matrix) may fail in cases where too many events diminish the phylogenetic signal. Thus, an approach comparing genetic distances in distinct genome regions (pairwise distance deviation matrix) was set up. In alpha, beta, and delta-coronaviruses, a low incidence of recombination between closely related viruses was evident in all genome regions, but it was more extensive between the spike gene and other genome regions. In contrast, avian gammacoronaviruses recombined extensively and exist as a global cloud of genes with poorly corresponding genetic distances in different parts of the genome. Spike, but not other structural proteins, was most commonly exchanged between coronaviruses. Recombination patterns differed between coronavirus genera and corresponded to the modular structure of the spike: recombination traces were more pronounced between spike domains (N-terminal and C-terminal parts of S1 and S2) than within domains. The variability of possible recombination events and their uneven distribution over the genome suggest that compatibility of genes, rather than mechanistic or ecological limitations, shapes recombination patterns in coronaviruses.


Assuntos
Coronavirus/classificação , Coronavirus/genética , Evolução Molecular , Variação Genética , Genoma Viral , Recombinação Genética , Animais , Aves/virologia , Infecções por Coronavirus/virologia , Filogenia , Proteínas Virais/genética
2.
BMC Plant Biol ; 21(1): 312, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215182

RESUMO

BACKGROUND: Peanut smut is a disease caused by the fungus Thecaphora frezii Carranza & Lindquist to which most commercial cultivars in South America are highly susceptible. It is responsible for severely decreased yield and no effective chemical treatment is available to date. However, smut resistance has been identified in wild Arachis species and further transferred to peanut elite cultivars. To identify the genome regions conferring smut resistance within a tetraploid genetic background, this study evaluated a RIL population {susceptible Arachis hypogaea subsp. hypogaea (JS17304-7-B) × resistant synthetic amphidiploid (JS1806) [A. correntina (K 11905) × A. cardenasii (KSSc 36015)] × A. batizocoi (K 9484)4×} segregating for the trait. RESULTS: A SNP based genetic map arranged into 21 linkage groups belonging to the 20 peanut chromosomes was constructed with 1819 markers, spanning a genetic distance of 2531.81 cM. Two consistent quantitative trait loci (QTLs) were identified qSmIA08 and qSmIA02/B02, located on chromosome A08 and A02/B02, respectively. The QTL qSmIA08 at 15.20 cM/5.03 Mbp explained 17.53% of the phenotypic variance, while qSmIA02/B02 at 4.0 cM/3.56 Mbp explained 9.06% of the phenotypic variance. The combined genotypic effects of both QTLs reduced smut incidence by 57% and were stable over the 3 years of evaluation. The genome regions containing the QTLs are rich in genes encoding proteins involved in plant defense, providing new insights into the genetic architecture of peanut smut resistance. CONCLUSIONS: A major QTL and a minor QTL identified in this study provide new insights into the genetic architecture of peanut smut resistance that may aid in breeding new varieties resistant to peanut smut.


Assuntos
Arachis/genética , Arachis/microbiologia , Mapeamento Cromossômico , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Locos de Características Quantitativas/genética , Estudos de Associação Genética , Marcadores Genéticos , Endogamia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Recombinação Genética/genética
3.
Acta Virol ; 65(2): 232-236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34130474

RESUMO

Feline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats. In this study, the complete genome sequence of FCV 14Q315, which was detected from a dead domestic cat with a hemorrhagic-like disease, was analyzed to identify the genetic characteristics. The FCV 14Q315 genome was 7,684 bp. Phylogenetic analyses based on the ORF1, ORF2, and ORF3 sequences indicated that FCV 14Q315 is more closely related to FCV 15D022 than to other FCV strains. ORF1 of FCV 14Q315 shared high sequence similarity with ORF1 of FCVs 15D022 and UTCVM-H1. We further evaluated genetic recombination in ORF1 of FCV 14Q315 and detected intergenic recombination between p30 and the ORF1/ORF2 junction with high significance. Particularly, the non-recombination region in ORF1 of FCV 14Q315 showed high sequence similarity with FCVs GX2019, CH-JL2, and 15D022. The recombination region in ORF1 of FCV 14Q315 showed the highest similarity with FCV UTCVM-H1, which is associated with a hemorrhagic-like disease. The results suggest that the UTCVM-H1-like FCV was introduced into the Republic of Korea and presumably recombined with Korean FCVs by occasional mixed infections. In addition, the Korean FCV strains were located in several phylogenetic clusters with marked genetic diversity in the ORF2 region. These results imply that Korean FCVs possess high genetic diversity owing to mutations and recombination. Furthermore, it is possible that certain FCVs caused cyclical infections in the Korean cat population based on a phylogenetic analysis of FCVs isolated at different time points. Keywords: calicivirus; virulent systemic feline calicivirus; recombination; hemorrhagic-like disease.


Assuntos
Infecções por Caliciviridae , Calicivirus Felino , Animais , Infecções por Caliciviridae/veterinária , Calicivirus Felino/genética , Gatos , Humanos , Filogenia , Recombinação Genética , República da Coreia
4.
Nat Commun ; 12(1): 3801, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155204

RESUMO

The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935-1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Genes Bacterianos/genética , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Alelos , Resistência às Cefalosporinas/efeitos dos fármacos , Resistência às Cefalosporinas/genética , Variação Genética , Genoma Bacteriano/genética , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/isolamento & purificação , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Estados Unidos/epidemiologia
5.
Nat Commun ; 12(1): 3846, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158481

RESUMO

CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/-Boris+/+, and Ctcf+/+Boris-/- males are fertile, Ctcf+/-Boris-/- (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are "toxic" to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.


Assuntos
Fator de Ligação a CCCTC/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Espermatogênese/genética , Testículo/metabolismo , Animais , Fator de Ligação a CCCTC/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Infertilidade Masculina/genética , Masculino , Meiose/genética , Camundongos Knockout , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA-Seq/métodos , Recombinação Genética , Espermatozoides/metabolismo
6.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068033

RESUMO

Conjugation, besides transformation and transduction, is one of the main mechanisms of horizontal transmission of genetic information among bacteria. Conjugational transfer, due to its essential role in shaping bacterial genomes and spreading of antibiotics resistance genes, has been widely studied for more than 70 years. However, new and intriguing facts concerning the molecular basis of this process are still being revealed. Most recently, a novel family of conjugative relaxases (Mob proteins) was distinguished. The characteristic feature of these proteins is that they are not related to any of Mobs described so far. Instead of this, they share significant similarity to tyrosine recombinases. In this study MobK-a tyrosine recombinase-like Mob protein, encoded by pIGRK cryptic plasmid from the Klebsiella pneumoniae clinical strain, was characterized. This study revealed that MobK is a site-specific nuclease and its relaxase activity is dependent on both a conserved catalytic tyrosine residue (Y179) that is characteristic of tyrosine recombinases and the presence of Mg2+ divalent cations. The pIGRK minimal origin of transfer sequence (oriT) was also characterized. This is one of the first reports presenting tyrosine recombinase-like conjugative relaxase protein. It also demonstrates that MobK is a convenient model for studying this new protein family.


Assuntos
Proteínas de Bactérias/metabolismo , Conjugação Genética , DNA Bacteriano/genética , Endodesoxirribonucleases/metabolismo , Klebsiella pneumoniae/enzimologia , Plasmídeos/genética , Recombinação Genética , Proteínas de Bactérias/genética , Sequência de Bases , Endodesoxirribonucleases/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/crescimento & desenvolvimento , Plasmídeos/metabolismo
7.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064885

RESUMO

Genetically modified (GM) crops possess some superior characteristics, such as high yield and insect resistance, but their biosafety has aroused broad public concern. Some genetic engineering technologies have recently been proposed to remove exogenous genes from GM crops. Few approaches have been applied to maintain advantageous traits, but excising exogenous genes in seeds or fruits from these hybrid crops has led to the generation of harvested food without exogenous genes. In a previous study, split-Cre mediated by split intein could recombine its structure and restore recombination activity in hybrid plants. In the current study, the recombination efficiency of split-Cre under the control of ovule-specific or pollen-specific promoters was validated by hybridization of transgenic Arabidopsis containing the improved expression vectors. In these vectors, all exogenous genes were flanked by two loxP sites, including promoters, resistance genes, reporter genes, and split-Cre genes linked to the reporter genes via LP4/2A. A gene deletion system was designed in which NCre was driven by proDD45, and CCre was driven by proACA9 and proDLL. Transgenic lines containing NCre were used as paternal lines to hybridize with transgenic lines containing CCre. Because this hybridization method results in no co-expression of the NCre and CCre genes controlled by reproduction-specific promoters in the F1 progeny, the desirable characteristics could be retained. After self-crossing in F1 progeny, the expression level and protein activity of reporter genes were detected, and confirmed that recombination of split-Cre had occurred and the exogenous genes were partially deleted. The gene deletion efficiency represented by the quantitative measurements of GUS enzyme activity was over 59%, with the highest efficiency of 73% among variable hybrid combinations. Thus, in the present study a novel dual reproductive cell-specific promoter-mediated gene deletion system was developed that has the potential to take advantage of the merits of GM crops while alleviating biosafety concerns.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Deleção de Genes , Integrases/metabolismo , Plantas Geneticamente Modificadas/genética , Regiões Promotoras Genéticas , Transgenes , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Engenharia Genética , Vetores Genéticos , Integrases/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Recombinação Genética , Reprodução
8.
Nat Commun ; 12(1): 3457, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103505

RESUMO

Bacillus subtilis is a soil bacterium that is competent for natural transformation. Genetically distinct B. subtilis swarms form a boundary upon encounter, resulting in killing of one of the strains. This process is mediated by a fast-evolving kin discrimination (KD) system consisting of cellular attack and defence mechanisms. Here, we show that these swarm antagonisms promote transformation-mediated horizontal gene transfer between strains of low relatedness. Gene transfer between interacting non-kin strains is largely unidirectional, from killed cells of the donor strain to surviving cells of the recipient strain. It is associated with activation of a stress response mediated by sigma factor SigW in the donor cells, and induction of competence in the recipient strain. More closely related strains, which in theory would experience more efficient recombination due to increased sequence homology, do not upregulate transformation upon encounter. This result indicates that social interactions can override mechanistic barriers to horizontal gene transfer. We hypothesize that KD-mediated competence in response to the encounter of distinct neighbouring strains could maximize the probability of efficient incorporation of novel alleles and genes that have proved to function in a genomically and ecologically similar context.


Assuntos
Bacillus subtilis/genética , Transferência Genética Horizontal , Adaptação Fisiológica , Membrana Celular/metabolismo , DNA Bacteriano/genética , Genoma Bacteriano , Mutação/genética , Nucleotídeos/genética , Recombinação Genética/genética , Estresse Fisiológico , Transformação Genética , Regulação para Cima
9.
Proc Biol Sci ; 288(1952): 20210729, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34102886

RESUMO

The ability to clone oneself has clear benefits-no need for mate hunting or dilution of one's genome in offspring. It is therefore unsurprising that some populations of haplo-diploid social insects have evolved thelytokous parthenogenesis-the virgin birth of a female. But thelytokous parthenogenesis has a downside: the loss of heterozygosity (LoH) as a consequence of genetic recombination. LoH in haplo-diploid insects can be highly deleterious because female sex determination often relies on heterozygosity at sex-determining loci. The two female castes of the Cape honeybee, Apis mellifera capensis, differ in their mode of reproduction. While workers always reproduce thelytokously, queens always mate and reproduce sexually. For workers, it is important to reduce the frequency of recombination so as to not produce offspring that are homozygous. Here, we ask whether recombination rates differ between Cape workers and Cape queens that we experimentally manipulated to reproduce thelytokously. We tested our hypothesis that Cape workers have evolved mechanisms that restrain genetic recombination, whereas queens have no need for such mechanisms because they reproduce sexually. Using a combination of microsatellite genotyping and whole-genome sequencing we find that a reduction in recombination is confined to workers only.


Assuntos
Repetições de Microssatélites , Partenogênese , Animais , Abelhas/genética , Feminino , Heterozigoto , Humanos , Partenogênese/genética , Recombinação Genética , Classe Social
10.
Environ Sci Technol ; 55(11): 7643-7653, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33983726

RESUMO

Recovering valuable materials from spent lithium-ion batteries is an important task because of the asymmetry in resource distribution, supply, and demand around the world. A lithium-ion battery is a combination system of various elements and their oxides. Current recovering technologies focus on the separation of valuable metal elements. They can inescapably bring secondary contamination and cost to the environment due to the addition of leachants and precipitants. To recover valuable materials, in situ recombination of elements in spent lithium-ion batteries can be a more economical and environment-friendly solution. Herein, we developed a technology based on in situ aluminothermic reduction and interstitial solid solution transformation to recover high-value γ-LiAlO2 and LiAl5O8 under vacuum and high-temperature (1723 K) conditions. It was found that the process of Li2O filling into the lattice of O-Al-O structure is an energy-reducing process, while LiAl5O8 was an existing high-energy transition-state matter. Since there was no wastewater generated, the process brought a new environment-friendly method for recovering valuable metals from spent lithium-ion batteries. This study also provides new comprehension regarding the design for high-value products' recovery from multi-element mixed wastes on an atomic scale.


Assuntos
Lítio , Reciclagem , Fontes de Energia Elétrica , Metais , Recombinação Genética
11.
Res Vet Sci ; 137: 217-225, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34023545

RESUMO

HoBi-like pestivirus, an emerging species within the Pestivirus genus, is an important pathogen associated with a variety of clinical manifestations of ruminants, especially cattle. HoBi-like pestiviruses were identified in several countries and from different hosts, and raised concerns with regard to their acute and persistent infections, which is implicated in economic losses for cattle farmers. However, the transmission path, codon usage bias, and host adaptation of the virus has not been studied. Hence, we performed the analysis the spatio-temporal transmission based on the available 5'-UTR sequences of HoBi-like pestivirus, and then conducted codon analysis of the complete coding sequence of the virus. The results show the virus appeared in 1952 (95% HPD: 1905-1985) and may have originated in India. In addition, Italy is the hub for the spread of the virus. Moreover, six potential recombination events and two complex recombination events were discovered. Analysis of codon usage patterns revealed that the effective number of codon (ENC) values with an average of 50.85, and the codon usage bias is greatly affected by natural selection, which is different from the previous BVDV-1, 2. Finally, codon adaptation index (CAI) analysis shows that pigs may be the potential origin species of the HoBi-like pestivirus. These findings will contribute to more effective control of the spread of the virus, extend the knowledge about the genetic and evolutionary features of HoBi-like viruses and provide some information for vaccine research.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Evolução Molecular , Pestivirus/genética , Regiões 5' não Traduzidas , Animais , Uso do Códon , Conjuntos de Dados como Assunto , Vírus da Diarreia Viral Bovina Tipo 1/genética , Interações entre Hospedeiro e Microrganismos , Índia , Itália , Fases de Leitura Aberta , Filogenia , Filogeografia , Recombinação Genética
13.
PLoS One ; 16(5): e0251368, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1242246

RESUMO

COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains' recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified, whereas samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. In addition, we structurally modelled the two most common mutations, Spike_D614G and Nsp12_P314L, which suggested that these linked mutations may enhance viral entry and replication, respectively. Overall, we propose that genomic recombination between different strains may contribute to SARS-CoV-2 virulence and COVID-19 severity and may present additional challenges for current treatment regimens and countermeasures. Furthermore, our study provides a possible explanation for the substantial second wave of COVID-19 presented with higher infection and death rates in many countries.


Assuntos
Recombinação Genética , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Virulência/fisiologia , COVID-19/patologia , COVID-19/virologia , Bases de Dados Genéticas , Variação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Simulação de Dinâmica Molecular , Mutação de Sentido Incorreto , Análise de Componente Principal , Estrutura Terciária de Proteína , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
15.
Nat Genet ; 53(6): 779-786, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33972781

RESUMO

Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.


Assuntos
Doença/genética , Variação Estrutural do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Característica Quantitativa Herdável , Alelos , LDL-Colesterol/metabolismo , Cromossomos Humanos/genética , Feminino , Frequência do Gene/genética , Humanos , Islândia , Modelos Lineares , Masculino , Pró-Proteína Convertase 9/genética , Recombinação Genética/genética , Deleção de Sequência/genética
16.
J Med Microbiol ; 70(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33999799

RESUMO

EV-D68 is an emerging enterovirus infection associated with severe acute respiratory illness (SARI), acute flaccid myelitis (AFM) and acute flaccid paralysis (AFP). While EV-D68 outbreaks and sporadic cases are reported globally, a single case has been reported from India. The present study aims to investigate the molecular epidemiology and clinical characteristics of EV-D68-associated SARI cases from South India. We screened influenza-negative archived throat swab specimens from Influenza-Like Illness (ILI) and SARI cases (n=959; 2016 to 2018 period) for enteroviruses by pan-enterovirus real-time RT-PCR. Thirteen samples positive for enteroviruses were typed by PCR and sequencing based on VPI, VP2 and/or 5'NCR regions. One EV-D68 RNA sample was subjected to next-generation sequencing for whole genome characterisation. Among 13 enterovirus cases, four were ECHO-11, three EV-D68, two CV-A16 and one each EV-71, CV-B1, CV-B2 and CV-A9. All three cases of EV-D68 infection were reported in children below 2 years of age from Kerala state of South India during June and July 2017. The patients developed pneumonia without any neurological complications. Sequencing based on VPI and 5'NCR regions showed that EV-D68 strains belong to the novel subclade B3. The EV-D68 complete genome identified with two unique amino acid substitutions in VP1 (T-246-I) and 3D (K-344-R) regions. This study reiterates the EV-D68 novel subclade B3 circulation in India and indicates the urgent need for structured EV-D68 surveillance in the country to describe the epidemiology.


Assuntos
Enterovirus Humano D/genética , Infecções por Enterovirus/virologia , Pneumonia Viral/virologia , Substituição de Aminoácidos , Proteínas do Capsídeo/genética , Enterovirus Humano D/classificação , Infecções por Enterovirus/epidemiologia , Feminino , Genoma Viral , Humanos , Índia/epidemiologia , Lactente , Masculino , Epidemiologia Molecular , Filogenia , Pneumonia Viral/epidemiologia , Polimorfismo Genético , Recombinação Genética , Proteínas Virais/química , Proteínas Virais/genética , Sequenciamento Completo do Genoma
17.
PLoS One ; 16(5): e0251368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34033650

RESUMO

COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains' recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified, whereas samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. In addition, we structurally modelled the two most common mutations, Spike_D614G and Nsp12_P314L, which suggested that these linked mutations may enhance viral entry and replication, respectively. Overall, we propose that genomic recombination between different strains may contribute to SARS-CoV-2 virulence and COVID-19 severity and may present additional challenges for current treatment regimens and countermeasures. Furthermore, our study provides a possible explanation for the substantial second wave of COVID-19 presented with higher infection and death rates in many countries.


Assuntos
Recombinação Genética , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Virulência/fisiologia , COVID-19/patologia , COVID-19/virologia , Bases de Dados Genéticas , Variação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Simulação de Dinâmica Molecular , Mutação de Sentido Incorreto , Análise de Componente Principal , Estrutura Terciária de Proteína , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
18.
Nat Commun ; 12(1): 2818, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990556

RESUMO

The sex pheromone system of ~160,000 moth species acts as a powerful form of assortative mating whereby females attract conspecific males with a species-specific blend of volatile compounds. Understanding how female pheromone production and male preference coevolve to produce this diversity requires knowledge of the genes underlying change in both traits. In the European corn borer moth, pheromone blend variation is controlled by two alleles of an autosomal fatty-acyl reductase gene expressed in the female pheromone gland (pgFAR). Here we show that asymmetric male preference is controlled by cis-acting variation in a sex-linked transcription factor expressed in the developing male antenna, bric à brac (bab). A genome-wide association study of preference using pheromone-trapped males implicates variation in the 293 kb bab intron 1, rather than the coding sequence. Linkage disequilibrium between bab intron 1 and pgFAR further validates bab as the preference locus, and demonstrates that the two genes interact to contribute to assortative mating. Thus, lack of physical linkage is not a constraint for coevolutionary divergence of female pheromone production and male behavioral response genes, in contrast to what is often predicted by evolutionary theory.


Assuntos
Genes de Insetos , Mariposas/genética , Mariposas/fisiologia , Atrativos Sexuais/genética , Atrativos Sexuais/fisiologia , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Alelos , Animais , Evolução Molecular , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Endogamia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Desequilíbrio de Ligação , Masculino , Preferência de Acasalamento Animal/fisiologia , Polimorfismo Genético , Locos de Características Quantitativas , Recombinação Genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Nat Commun ; 12(1): 2981, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016985

RESUMO

The spatial folding of chromosomes inside the nucleus has regulatory effects on gene expression, yet the impact of genome reshuffling on this organization remains unclear. Here, we take advantage of chromosome conformation capture in combination with single-nucleotide polymorphism (SNP) genotyping and analysis of crossover events to study how the higher-order chromatin organization and recombination landscapes are affected by chromosomal fusions in the mammalian germ line. We demonstrate that chromosomal fusions alter the nuclear architecture during meiosis, including an increased rate of heterologous interactions in primary spermatocytes, and alterations in both chromosome synapsis and axis length. These disturbances in topology were associated with changes in genomic landscapes of recombination, resulting in detectable genomic footprints. Overall, we show that chromosomal fusions impact the dynamic genome topology of germ cells in two ways: (i) altering chromosomal nuclear occupancy and synapsis, and (ii) reshaping landscapes of recombination.


Assuntos
Cromatina/metabolismo , Cromossomos/metabolismo , Recombinação Genética , Espermatócitos/metabolismo , Animais , Evolução Biológica , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Cromatina/genética , Pareamento Cromossômico/genética , Segregação de Cromossomos , Cromossomos/genética , Europa (Continente) , Fertilidade/genética , Técnicas de Genotipagem/métodos , Masculino , Camundongos , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Análise do Sêmen , Espermatócitos/citologia
20.
Cell Host Microbe ; 29(5): 675-677, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33984272

RESUMO

CRISPR transposons (CASTs) represent unique mobile genetic elements that co-opted CRISPR-Cas immune systems for RNA-guided DNA transposition. However, CAST-encoded CRISPR arrays rarely match the CAST's chromosomal location. A recent publication in Cell helps resolve this paradox by revealing CRISPR-array-independent mechanisms of chromosomal homing unique to different CAST types.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Elementos de DNA Transponíveis , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Recombinação Genética
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