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1.
Viruses ; 16(5)2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38793690

RESUMEN

The Mayaro virus (MAYV) is an arbovirus with emerging potential, though with a limited understanding of its epidemiology and evolution due to the lack of studies and surveillance. Here, we investigated 71 MAYV genome sequences from the Americas available at GenBank and characterized the phylogenetic relationship among virus strains. A phylogenetic analysis showed that sequences were grouped according to the genotypes L, D, and N. Genotype D sequences were closely related to sequences collected in adjacent years and from their respective countries, suggesting that isolates may have originated from circulating lineages. The coalescent analysis demonstrated similar results, indicating the continuous circulation of the virus between countries as well. An unidentified sequence from the USA was grouped with genotype D, suggesting the insertion of this genotype in the country. Furthermore, the recombination analysis detected homologous and three heterologous hybrids which presented an insertion into the nsP3 protein. Amino acid substitutions among sequences indicated selective pressure sites, suggesting viral adaptability. This also impacted the binding affinity between the E1-E2 protein complex and the Mxra8 receptor, associated with MAYV entry into human cells. These results provide information for a better understanding of genotypes circulating in the Americas.


Asunto(s)
Evolución Molecular , Variación Genética , Genoma Viral , Genotipo , Filogenia , Américas/epidemiología , Humanos , Alphavirus/genética , Alphavirus/clasificación , Alphavirus/aislamiento & purificación , Animales , Recombinación Genética , Infecciones por Alphavirus/virología , Infecciones por Alphavirus/epidemiología
2.
Viruses ; 16(3)2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38543811

RESUMEN

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral therapies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants which strongly challenged containment measures and some therapeutic treatments. To assess whether impaired immunity could lead to the increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimise the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients experienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low-frequency mutations. This study suggests that a compromised immune system alone does not affect SARS-CoV-2 within-host genomic variability.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , Mutación , Cuasiespecies
3.
Vavilovskii Zhurnal Genet Selektsii ; 27(7): 884-889, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38213711

RESUMEN

The light emitted by a luminescent bacterium serves as a unique native channel of information regarding the intracellular processes within the individual cell. In the presence of highly sensitive equipment, it is possible to obtain the distribution of bacterial culture cells by the intensity of light emission, which correlates with the amount of luciferase in the cells. When growing on rich media, the luminescence intensity of individual cells of brightly luminous strains of the luminescent bacteria Photobacterium leiognathi and Ph. phosporeum reaches 104-105 quanta/s. The signal of such intensity can be registered using sensitive photometric equipment. All experiments were carried out with bacterial clones (genetically homogeneous populations). A typical dynamics of luminous bacterial cells distributions with respect to intensity of light emission at various stages of batch culture growth in a liquid medium was obtained. To describe experimental distributions, a phenomenological model that links the light of a bacterial cell with the history of events at the molecular level was constructed. The proposed phenomenological model with a minimum number of fitting parameters (1.5) provides a satisfactory description of the complex process of formation of cell distributions by luminescence intensity at different stages of bacterial culture growth. This may be an indication that the structure of the model describes some essential processes of the real system. Since in the process of division all cells go through the stage of release of all regulatory molecules from the DNA molecule, the resulting distributions can be attributed not only to luciferase, but also to other proteins of constitutive (and not only) synthesis.

4.
Infect Genet Evol ; 103: 105342, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35878820

RESUMEN

Species belonging to the Leishmania (Viannia) subgenus are important causative agents of cutaneous and mucocutaneous leishmaniasis in Central and South America. These parasites possess several distinctive biological features that are influenced by their genetics, population structure, and genome instability. To date, several studies have revealed varying degrees of genetic diversity within Leishmania species. Particularly, in species of the L. (Viannia) subgenus, a generalized high intraspecific genetic diversity has been reported, although, conflicting conclusions have been drawn using different molecular techniques. Despite being the most common Leishmania species circulating in Panama and Colombia, few studies have analyzed clinical samples of Leishmania panamensis using whole-genome sequencing, and their restricted number of samples has limited the information they can provide to understand the population structure of L. panamensis. Here, we used next generation sequencing (NGS) to explore the genetic diversity of L. panamensis within its endemic range, analyzing data from 43 isolates of Colombian and Panamanian origin. Our results show the occurrence of three well-defined geographically correlated groups, and suggests the possible occurrence of additional phylogeographic groups. Furthermore, these results support the existence of a mixed mode of reproduction in L. panamensis, with varying frequencies of events of genetic recombination occurring primarily within subpopulations of closely related strains. This study offers important insights into the population genetics and reproduction mode of L. panamensis, paving the way to better understand their population structure and the emergence and maintenance of key eco-epidemiological traits.


Asunto(s)
Leishmania braziliensis , Leishmania guyanensis , Leishmania , Variación Genética , Genómica , Leishmania guyanensis/genética
5.
World J Gastroenterol ; 28(12): 1226-1238, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35431515

RESUMEN

Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Virus de la Hepatitis E , Hepatitis E , Antivirales/uso terapéutico , Femenino , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis E/complicaciones , Hepatitis E/diagnóstico , Hepatitis E/tratamiento farmacológico , Virus de la Hepatitis E/genética , Humanos , Filogenia , Embarazo
6.
BMC Infect Dis ; 22(1): 322, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35365069

RESUMEN

The world has been dealing with the SARS-COV-2 pandemic since December 2019 and a lot of effort has focused on tracking the spread of the virus by gathering information regarding testing statistics and generating viral genomic sequences. Unfortunately, there is neither a single comprehensive resource with global historical testing data nor a centralized database with summary statistics of the identified genomic variants. We merged different pre-aggregated historical testing data and complemented them with our manually extracted ones, which consist of 6852 historical test statistics from 76 countries/states unreported in any other dataset, at the date of submission, making our dataset the most comprehensive to date. We also analyzed all publicly deposited SARS-CoV-2 genomic sequences in GISAID and annotated their variants. Both datasets can be accessed through our interactive dashboard which also provides important insights on different outbreak trends across countries and states. The dashboard is available at https://bioinfo.lau.edu.lb/gkhazen/covid19 . A daily updated version of the datasets can be downloaded from github.com/KhazenLab/covid19-data.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Brotes de Enfermedades , Genoma Viral , Genómica , Humanos , SARS-CoV-2/genética
7.
Front Microbiol ; 13: 767912, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35283840

RESUMEN

The insertion sequence (IS) 6110 is a repetitive mobile element specific for the Mycobacterium tuberculosis complex (MTBC) used for years to diagnose and genotype this pathogen. It contains the overlapping reading frames orfA and orfB that encode a transposase. Its genetic variability is difficult to study because multiple copies are present in the genome. IS6110 is randomly located, nevertheless some preferential locations have been reported, which could be related to the behaviour of the strains. The aim of this work was to determine the intra- and inter-strain genetic conservation of this element in the MTBC. For this purpose, we analysed 158 sequences of IS6110 copies from 55 strains. Eighty-four copies were from 17 strains for which we knew all the locations in their genome. In addition, we studied 74 IS6110 copies in 38 different MTBC strains in which the location was characteristic of different families including Haarlem, LAM, S, and L6 strains. We observed mutation in 13.3% of the copies studied and we found 10 IS6110 variants in 21 copies belonging to 16 strains. The high copy number strains showed 6.2% of their IS6110 copies mutated, in contrast with the 31.1% in the low-copy-number strains. The apparently more ancient copy localised in the DR region was that with more variant copies, probably because this was the most studied location. Notably, all Haarlem and X family strains studied have an IS6110 in Rv0403c, suggesting a common origin for both families. Nevertheless, we detected a variant specific for the X family that would have occurred in this location after the phylogenetic separation. This variant does not prevent transposition although it may occur at a lower frequency, as X strains remain with low copy number (LCN) of IS6110.

8.
Mem. Inst. Oswaldo Cruz ; 117: e210193, 2022. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1375913

RESUMEN

Trypanosoma cruzi, the agent of Chagas disease (ChD), exhibits remarkable biological and genetic diversity, along with eco-epidemiological complexity. In order to facilitate communication among researchers aiming at the characterisation of biological and epidemiological aspects of T. cruzi, parasite isolates and strains were partitioned into seven discrete typing units (DTUs), TcI-TcVI and TcBat, identifiable by reproducible genotyping protocols. Here we present the potential origin of the genetic diversity of T. cruzi and summarise knowledge about eco-epidemiological associations of DTUs with mammalian reservoirs and vectors. Circumstantial evidence of a connection between T. cruzi genotype and ChD manifestations is also discussed emphasising the role of the host's immune response in clinical ChD progression. We describe genomic aspects of DTUs focusing on polymorphisms in multigene families encoding surface antigens that play essential functions for parasite survival both in the insect vector and the mammalian host. Such antigens most probably contributed to the parasite success in establishing infections in different hosts and exploring several niches. Gaps in the current knowledge and challenges for future research are pointed out.

9.
Genome Biol ; 22(1): 347, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-34930391

RESUMEN

BACKGROUND: Genomic structural variations (SV) are important determinants of genotypic and phenotypic changes in many organisms. However, the detection of SV from next-generation sequencing data remains challenging. RESULTS: In this study, DNA from a Chinese family quartet is sequenced at three different sequencing centers in triplicate. A total of 288 derivative data sets are generated utilizing different analysis pipelines and compared to identify sources of analytical variability. Mapping methods provide the major contribution to variability, followed by sequencing centers and replicates. Interestingly, SV supported by only one center or replicate often represent true positives with 47.02% and 45.44% overlapping the long-read SV call set, respectively. This is consistent with an overall higher false negative rate for SV calling in centers and replicates compared to mappers (15.72%). Finally, we observe that the SV calling variability also persists in a genotyping approach, indicating the impact of the underlying sequencing and preparation approaches. CONCLUSIONS: This study provides the first detailed insights into the sources of variability in SV identification from next-generation sequencing and highlights remaining challenges in SV calling for large cohorts. We further give recommendations on how to reduce SV calling variability and the choice of alignment methodology.


Asunto(s)
Variación Estructural del Genoma , Genómica/métodos , Células Germinativas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuencia de Bases , Sesgo , Mapeo Cromosómico , Análisis de Secuencia de ADN
10.
Acta Trop ; 222: 106053, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34273311

RESUMEN

All trypanosomatid genomes are colonized by non-LTR retrotransposons which exhibit a highly conserved 77-nt sequence at their 5' ends, known as the Pr77-hallmark (Pr77). The wide distribution of Pr77 is expected to be related to the gene regulation processes in these organisms as it has promoter and HDV-like ribozyme activities at the DNA and RNA levels, respectively. The identification of Pr77 hallmark-bearing retrotransposons and the study of the associations of mobile elements with relevant genes have been analyzed in the genomes of six strains of Trypanosoma cruzi belonging to different discrete typing units (DTUs) and with different geographical origins and host/vectors. The genomes have been sequenced, assembled and annotated. BUSCO analyses indicated a good quality for the assemblies that were used in comparative analyses. The results show differences among the six genomes in the copy number of genes related to virulence processes, the abundance of retrotransposons bearing the Pr77 sequence and the presence of the Pr77 hallmarks not associated with retroelements. The analyses also show frequent associations of Pr77-bearing retrotransposons and single Pr77 hallmarks with genes coding for trans-sialidases, RHS, MASP or hypothetical proteins, showing variable proportion depending on the type of retroelement, gene class and parasite strain. These differences in the genomic distribution of active retroelements and other Pr77-containing elements have shaped the genome architecture of these six strains and might be contributing to the phenotypic variability existing among them.


Asunto(s)
Retroelementos , Trypanosoma cruzi , Regulación de la Expresión Génica , Genoma de Protozoos , Regiones Promotoras Genéticas , Retroelementos/genética , Trypanosoma cruzi/genética
11.
Life (Basel) ; 11(4)2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33919874

RESUMEN

Zika virus (ZIKV), without a vaccine or an effective treatment approved to date, has globally spread in the last century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in recent years, causing epidemics with greater infectivity, tropism towards new tissues and other related symptoms as a product of various emergent ZIKV-host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, the genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons have barely been studied. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 410 complete genomes in a phylogenomic scanning were used to study the conservation of structured RNAs. Our results show the contemporary landscape of conserved structured regions with unique conserved structured regions in clades or in lineages within circulating ZIKV strains. We propose these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that lead to ZIKV populations to acquire nucleotide substitutions, which is evidence of the local structure genome differentiation.

12.
Electron J Biotechnol ; 49: 22-28, Jan. 2021. ilus, graf, tab
Artículo en Inglés | LILACS | ID: biblio-1291938

RESUMEN

BACKGROUND: Vibrio species display variable and plastic fitness strategies to survive and interact with multiple hosts, including marine aquaculture species that are severely affected by pathogenic Vibrios. The culturable Vibrio sp. strain ArtGut-C1, the focus of this study, provides new evidence of such phenotypic plasticity as it accumulates polyhydroxybutyrate (PHB), a biodegradable polymer with anti-pathogen activity, particularly in the marine larviculture phase. The strain was isolated from the gut of laboratory-reared Artemia individuals, the live diet and PHB carrier used in larviculture. Its main phenotypic properties, taxonomic status and genomic properties are reported based on the whole-genome sequencing. RESULTS: Vibrio sp. ArtGut-C1 yielded 72.6% PHB of cells' dry weight at 25 C. The genomic average nucleotide identity (ANI) shows it is closely related to V. diabolicus (ANI: 88.6%). Its genome contains 5,236,997- bp with 44.8% GC content, 3,710 protein-coding sequences, 96 RNA, 9 PHB genes functionally related to PHB metabolic pathways, and several genes linked to competing and colonizing abilities. CONCLUSIONS: This culturable PHB-accumulating Vibrio strain shows high genomic and phenotypic variability. It may be used as a natural pathogen biocontrol in the marine hatchery and as a potential cell factory for PHB production.


Asunto(s)
Animales , Artemia/microbiología , Vibrio/metabolismo , Polihidroxialcanoatos/metabolismo , Hidroxibutiratos/metabolismo , Variación Genética , Vibrio/aislamiento & purificación , Vibrio/clasificación , Acuicultura , Probióticos , Crustáceos/microbiología , Microbioma Gastrointestinal , Variación Biológica Poblacional
13.
Front Cell Infect Microbiol ; 10: 582192, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33178631

RESUMEN

Leishmania (Viannia) braziliensis is an important Leishmania species circulating in several Central and South American countries. Among Leishmania species circulating in Brazil, Argentina and Colombia, L. braziliensis has the highest genomic variability. However, genomic variability at the whole genome level has been only studied in Brazilian and Peruvian isolates; to date, no Colombian isolates have been studied. Considering that in Colombia, L. braziliensis is a species with great clinical and therapeutic relevance, as well as the role of genetic variability in the epidemiology of leishmaniasis, we analyzed and evaluated intraspecific genomic variability of L. braziliensis from Colombian and Bolivian isolates and compared them with Brazilian isolates. Twenty-one genomes were analyzed, six from Colombian patients, one from a Bolivian patient, and 14 Brazilian isolates downloaded from public databases. The results obtained of Phylogenomic analysis showed the existence of four well-supported clades, which evidenced intraspecific variability. The whole-genome analysis revealed structural variations in the somy, mainly in the Brazilian genomes (clade 1 and clade 3), low copy number variations, and a moderate number of single-nucleotide polymorphisms (SNPs) in all genomes analyzed. Interestingly, the genomes belonging to clades 2 and 3 from Colombia and Brazil, respectively, were characterized by low heterozygosity (~90% of SNP loci were homozygous) and regions suggestive of loss of heterozygosity (LOH). Additionally, we observed the drastic whole genome loss of heterozygosity and possible hybridization events in one genome belonging to clade 4. Unique/shared SNPs between and within the four clades were identified, revealing the importance of some of them in biological processes of L. braziliensis. Our analyses demonstrate high genomic variability of L. braziliensis in different regions of South America, mainly in Colombia and suggest that this species exhibits striking genomic diversity and a capacity of genomic hybridization; additionally, this is the first study to report whole-genome sequences of Colombian L. braziliensis isolates.


Asunto(s)
Leishmania braziliensis , Argentina , Brasil , Colombia/epidemiología , Variaciones en el Número de Copia de ADN , Genómica , Humanos , Leishmania braziliensis/genética , Hibridación de Ácido Nucleico
14.
Front Immunol ; 11: 510943, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33117335

RESUMEN

Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) is a geographically widespread and economically devastating pathogen that colonizes ciliated epithelium; the infection of Mhp can damnify the mucociliary functions as well as leading to Mycoplasma pneumonia of swine (MPS). MPS is a chronic respiratory infectious disease with high infectivity, and the mortality can be increased by secondary infections as the host immunity gets down-regulated during Mhp infection. The host immune responses are regarded as the main driving force for the disease development, while MPS is prone to attack repeatedly in farms even with vaccination or other treatments. As one of the smallest microorganisms with limited genome scale and metabolic pathways, Mhp can use several mechanisms to achieve immune evasion effect and derive enough nutrients from its host, indicating that there is a strong interaction between Mhp and porcine organism. In this review, we summarized the immune evasion mechanisms from genomic variability and post-translational protein processing. Besides, Mhp can induce the immune cells apoptosis by reactive oxygen species production, excessive nitric oxide (NO) release and caspase activation, and stimulate the release of cytokines to regulate inflammation. This article seeks to provide some new points to reveal the complicated interaction between the pathogen and host immune system with Mhp as a typical example, further providing some new strategies for the vaccine development against Mhp infection.


Asunto(s)
Proteínas Bacterianas/inmunología , Mycoplasma hyopneumoniae/inmunología , Neumonía Porcina por Mycoplasma/inmunología , Procesamiento Proteico-Postraduccional/inmunología , Porcinos/inmunología , Animales
15.
Genes (Basel) ; 11(3)2020 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-32120946

RESUMEN

Leishmania (Viannia) panamensis is one of the most important Leishmania species associated with cutaneous leishmaniasis (CL) in Latin America. Despite its wide geographic distribution and pathogenic potential in humans and animals, the genomic variability of this species is low compared with other Leishmania species circulating in the same geographical area. No studies have reported a detailed analysis of the whole genome of L. panamensis from clinical isolates using DNA high-throughput sequencing to clarify its intraspecific genomic variability or plausible divergence. Therefore, this study aimed to evaluate the intraspecific genomic variability of L. panamensis from Colombia and Panama. A total of 22 genomes were analyzed, 19 from Colombian patients with CL and three genomes from Panama obtained from public databases. The phylogenomic analysis revealed the potential existence of three well-supported clades as evidence of intraspecific divergence. Additionally, the whole-genome analysis showed low structural variations in terms of ploidy, copy number variations, and single-nucleotide polymorphisms (SNPs). SNPs shared among all clades were identified, revealing their importance in different biological processes of L. panamensis. The findings not only expand our knowledge of intraspecific genomic variability of one of the most important Leishmania species in South America but also highlights the possible existence of different clades/lineages/subpopulations across a geographic scale.


Asunto(s)
Variación Genética/genética , Genómica , Leishmania/genética , Leishmaniasis Cutánea/genética , Adolescente , Adulto , Anciano , Animales , Colombia/epidemiología , Variaciones en el Número de Copia de ADN/genética , Femenino , Genoma/genética , Variación Estructural del Genoma/genética , Humanos , Leishmania/patogenicidad , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Masculino , Persona de Mediana Edad , Panamá/epidemiología , Filogenia , Polimorfismo de Nucleótido Simple/genética , América del Sur/epidemiología , Adulto Joven
16.
Microbiologyopen ; 9(2): e974, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31797576

RESUMEN

Halobacterium salinarum is an extremely halophilic archaeon that is widely distributed in hypersaline environments and was originally isolated as a spoilage organism of salted fish and hides. The type strain 91-R6 (DSM 3754T ) has seldom been studied and its genome sequence has only recently been determined by our group. The exact relationship between the type strain and two widely used model strains, NRC-1 and R1, has not been described before. The genome of Hbt. salinarum strain 91-R6 consists of a chromosome (2.17 Mb) and two large plasmids (148 and 102 kb, with 39,230 bp being duplicated). Cytosine residues are methylated (m4 C) within CTAG motifs. The genomes of type and laboratory strains are closely related, their chromosomes sharing average nucleotide identity (ANIb) values of 98% and in silico DNA-DNA hybridization (DDH) values of 95%. The chromosomes are completely colinear, do not show genome rearrangement, and matching segments show <1% sequence difference. Among the strain-specific sequences are three large chromosomal replacement regions (>10 kb). The well-studied AT-rich island (61 kb) of the laboratory strains is replaced by a distinct AT-rich sequence (47 kb) in 91-R6. Another large replacement (91-R6: 78 kb, R1: 44 kb) codes for distinct homologs of proteins involved in motility and N-glycosylation. Most (107 kb) of plasmid pHSAL1 (91-R6) is very closely related to part of plasmid pHS3 (R1) and codes for essential genes (e.g. arginine-tRNA ligase and the pyrimidine biosynthesis enzyme aspartate carbamoyltransferase). Part of pHS3 (42.5 kb total) is closely related to the largest strain-specific sequence (164 kb) in the type strain chromosome. Genome sequencing unraveled the close relationship between the Hbt. salinarum type strain and two well-studied laboratory strains at the DNA and protein levels. Although an independent isolate, the type strain shows a remarkably low evolutionary difference to the laboratory strains.


Asunto(s)
Genoma Arqueal , Genómica , Halobacterium salinarum/genética , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Evolución Biológica , Biología Computacional/métodos , Orden Génico , Heterogeneidad Genética , Genómica/métodos , Anotación de Secuencia Molecular , Plásmidos
17.
Bio Protoc ; 10(24): e3871, 2020 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-33659508

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; initially named 2019-nCoV) is responsible for the recent coronavirus disease (COVID-19) pandemic, and polymerase chain reaction (PCR) is the current standard method for diagnosis from patient samples. As PCR assays are prone to sequence mismatches due to mutations in the viral genome, it is important to verify the genomic variability at primer/probe binding regions periodically. This step-by-step protocol describes a bioinformatics approach for an extensive evaluation of the sequence variability within the primer/probe target regions of the SARS-CoV-2 genome. The protocol can be applied to any molecular diagnostic assay of choice using freely available software programs and the ready-to-use multiple sequence alignment (MSA) file provided. Graphic abstract Overview of the sequence tracing protocol. The figure was created using the Library of Science and Medical Illustrations from somersault18:24 licensed under a CC BY-NC-SA 4.0 license (https://creativecommons.org/licenses/by-nc-sa/4.0/). Video abstract: https://youtu.be/M1lV1liWE9k.

18.
Front Psychiatry ; 11: 593233, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33551865

RESUMEN

Twentieth-century genetics was hard put to explain the irregular behavior of neuropsychiatric disorders. Autism and schizophrenia defy a principle of natural selection; they are highly heritable but associated with low reproductive success. Nevertheless, they persist. The genetic origins of such conditions are confounded by the problem of variable expression, that is, when a given genetic aberration can lead to any one of several distinct disorders. Also, autism and schizophrenia occur on a spectrum of severity, from mild and subclinical cases to the overt and disabling. Such irregularities reflect the problem of missing heritability; although hundreds of genes may be associated with autism or schizophrenia, together they account for only a small proportion of cases. Techniques for higher resolution, genomewide analysis have begun to illuminate the irregular and unpredictable behavior of the human genome. Thus, the origins of neuropsychiatric disorders in particular and complex disease in general have been illuminated. The human genome is characterized by a high degree of structural and behavioral variability: DNA content variation, epistasis, stochasticity in gene expression, and epigenetic changes. These elements have grown more complex as evolution scaled the phylogenetic tree. They are especially pertinent to brain development and function. Genomic variability is a window on the origins of complex disease, neuropsychiatric disorders, and neurodevelopmental disorders in particular. Genomic variability, as it happens, is also the fuel of evolvability. The genomic events that presided over the evolution of the primate and hominid lineages are over-represented in patients with autism and schizophrenia, as well as intellectual disability and epilepsy. That the special qualities of the human genome that drove evolution might, in some way, contribute to neuropsychiatric disorders is a matter of no little interest.

19.
Front Genet ; 10: 865, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31620169

RESUMEN

Tuberculosis (TB), caused by the human pathogens Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum, has plagued humanity for millennia and remains the deadliest infectious disease in the modern world. Mycobacterium tuberculosis and M. africanum can be subdivided phylogenetically into seven lineages exhibiting a low but significant degree of genomic diversity and preferential geographic distributions. Human genetic variability impacts all stages of TB pathogenesis ranging from susceptibility to infection with Mtb, progression of infection to disease, and the development of distinct clinical subtypes. The genetic study of severe childhood TB identified strong inborn single-gene errors revealing crucial pathways of vulnerability to TB. However, the identification of major TB-susceptibility genes on the population level has remained elusive. In particular, the replication of findings from candidate and genome-wide association studies across distinct human populations has proven difficult, thus hampering the characterization of reliable host molecular markers of susceptibility. Among the possible confounding factors of genetic association studies is Mtb genomic variability, which generally was not taken into account by human genetic studies. In support of this possibility, Mtb lineage was found to be a contributing factor to clinical presentation of TB and epidemiological spread of Mtb in exposed populations. The confluence of pathogen and human host genetic variability to TB pathogenesis led to the consideration of a possible coadaptation of Mtb strains and their human hosts, which should reveal itself in significant interaction effects between Mtb strain and TB-susceptibility/resistance alleles. Here, we present some of the most consistent findings of genetic susceptibility factors in human TB and review studies that point to genome-to-genome interaction between humans and Mtb lineages. The limited results available so far suggest that analyses considering joint human-Mtb genomic variability may provide improved power for the discovery of pathogenic drivers of the ongoing TB epidemic.

20.
BMC Genomics ; 19(1): 816, 2018 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-30424726

RESUMEN

BACKGROUND: Trypanosoma cruzi, the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. TcII is among the major DTUs enrolled in human infections in South America southern cone, where it is associated with severe cardiac and digestive symptoms. Despite the importance of TcII in Chagas disease epidemiology and pathology, so far, no genome-wide comparisons of the mitochondrial and nuclear genomes of TcII field isolates have been performed to track the variability and evolution of this DTU in endemic regions. RESULTS: In the present work, we have sequenced and compared the whole nuclear and mitochondrial genomes of seven TcII strains isolated from chagasic patients from the central and northeastern regions of Minas Gerais, Brazil, revealing an extensive genetic variability within this DTU. A comparison of the phylogeny based on the nuclear or mitochondrial genomes revealed that the majority of branches were shared by both sequences. The subtle divergences in the branches are probably consequence of mitochondrial introgression events between TcII strains. Two T. cruzi strains isolated from patients living in the central region of Minas Gerais, S15 and S162a, were clustered in the nuclear and mitochondrial phylogeny analysis. These two strains were isolated from the other five by the Espinhaço Mountains, a geographic barrier that could have restricted the traffic of insect vectors during T. cruzi evolution in the Minas Gerais state. Finally, the presence of aneuploidies was evaluated, revealing that all seven TcII strains have a different pattern of chromosomal duplication/loss. CONCLUSIONS: Analysis of genomic variability and aneuploidies suggests that there is significant genomic variability within Minas Gerais TcII strains, which could be exploited by the parasite to allow rapid selection of favorable phenotypes. Also, the aneuploidy patterns vary among T. cruzi strains and does not correlate with the nuclear phylogeny, suggesting that chromosomal duplication/loss are recent and frequent events in the parasite evolution.


Asunto(s)
Aneuploidia , Enfermedad de Chagas/parasitología , Variación Genética , Genoma de Protozoos , Proteínas Protozoarias/genética , Trypanosoma cruzi/genética , Secuenciación Completa del Genoma/métodos , Animales , Enfermedad de Chagas/transmisión , ADN Protozoario/genética , Genotipo , Humanos , Insectos Vectores/parasitología , Tipificación Molecular , Filogenia , Trypanosoma cruzi/clasificación , Trypanosoma cruzi/aislamiento & purificación
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