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1.
Genome Res ; 32(1): 203-213, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34764149

RESUMEN

Cryptosporidiosis is a leading cause of waterborne diarrheal disease globally and an important contributor to mortality in infants and the immunosuppressed. Despite its importance, the Cryptosporidium community has only had access to a good, but incomplete, Cryptosporidium parvum IOWA reference genome sequence. Incomplete reference sequences hamper annotation, experimental design, and interpretation. We have generated a new C. parvum IOWA genome assembly supported by Pacific Biosciences (PacBio) and Oxford Nanopore long-read technologies and a new comparative and consistent genome annotation for three closely related species: C. parvum, Cryptosporidium hominis, and Cryptosporidium tyzzeri We made 1926 C. parvum annotation updates based on experimental evidence. They include new transporters, ncRNAs, introns, and altered gene structures. The new assembly and annotation revealed a complete Dnmt2 methylase ortholog. Comparative annotation between C. parvum, C. hominis, and C. tyzzeri revealed that most "missing" orthologs are found, suggesting that the biological differences between the species must result from gene copy number variation, differences in gene regulation, and single-nucleotide variants (SNVs). Using the new assembly and annotation as reference, 190 genes are identified as evolving under positive selection, including many not detected previously. The new C. parvum IOWA reference genome assembly is larger, gap free, and lacks ambiguous bases. This chromosomal assembly recovers all 16 chromosome ends, 13 of which are contiguously assembled. The three remaining chromosome ends are provisionally placed. These ends represent duplication of entire chromosome ends including subtelomeric regions revealing a new level of genome plasticity that will both inform and impact future research.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Criptosporidiosis/genética , Cryptosporidium/genética , Variaciones en el Número de Copia de ADN , Genoma , Humanos , Telómero/genética
2.
Emerg Infect Dis ; 28(6): 1211-1223, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35608628

RESUMEN

Vertical transmission of leishmaniasis is common but is difficult to study against the background of pervasive vector transmission. We present genomic data from dogs in the United States infected with Leishmania infantum parasites; these infections have persisted in the apparent absence of vector transmission. We demonstrate that these parasites were introduced from the Old World separately and more recently than L. infantum from South America. The parasite population shows unusual genetics consistent with a lack of meiosis: a high level of heterozygous sites shared across all isolates and no decrease in linkage with genomic distance between variants. Our data confirm that this parasite population has been evolving with little or no sexual reproduction. This demonstration of vertical transmission has profound implications for the population genetics of Leishmania parasites. When investigating transmission in complex natural settings, considering vertical transmission alongside vector transmission is vital.


Asunto(s)
Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Parásitos , Animales , Perros , Enfermedades de los Perros/parasitología , Transmisión Vertical de Enfermedad Infecciosa , Leishmania infantum/genética , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/veterinaria , Estados Unidos/epidemiología , Perros de Trabajo
3.
PLoS Genet ; 15(11): e1008452, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31710597

RESUMEN

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied-despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania.


Asunto(s)
Interacciones Huésped-Parásitos/genética , Leishmania/genética , Psychodidae/parasitología , Trypanosomatina/genética , Animales , Drosophila melanogaster/genética , Drosophila melanogaster/parasitología , Infecciones por Euglenozoos/genética , Infecciones por Euglenozoos/parasitología , Infecciones por Euglenozoos/transmisión , Humanos , Insectos Vectores/genética , Leishmania/patogenicidad , Leishmaniasis/genética , Leishmaniasis/parasitología , Leishmaniasis/transmisión , Psychodidae/genética , Trypanosomatina/patogenicidad
4.
PLoS Genet ; 15(5): e1008042, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31091230

RESUMEN

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97-99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes.


Asunto(s)
Genoma de Protozoos , Leishmania infantum/genética , Leishmania major/genética , Leishmania tropica/genética , Animales , Secuencia de Bases , Quimera , Mapeo Cromosómico , Cruzamientos Genéticos , Genotipo , Patrón de Herencia , Insectos Vectores/parasitología , Leishmania infantum/metabolismo , Leishmania major/metabolismo , Leishmania tropica/metabolismo , Meiosis , Psychodidae/parasitología , Recombinación Genética , Secuenciación Completa del Genoma
5.
Proc Natl Acad Sci U S A ; 109(4): 1269-74, 2012 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-22232693

RESUMEN

The mammalian gut harbors a dense microbial community interacting in multiple ways, including horizontal gene transfer (HGT). Pangenome analyses established particularly high levels of genetic flux between Gram-negative Enterobacteriaceae. However, the mechanisms fostering intraenterobacterial HGT are incompletely understood. Using a mouse colitis model, we found that Salmonella-inflicted enteropathy elicits parallel blooms of the pathogen and of resident commensal Escherichia coli. These blooms boosted conjugative HGT of the colicin-plasmid p2 from Salmonella enterica serovar Typhimurium to E. coli. Transconjugation efficiencies of ~100% in vivo were attributable to high intrinsic p2-transfer rates. Plasmid-encoded fitness benefits contributed little. Under normal conditions, HGT was blocked by the commensal microbiota inhibiting contact-dependent conjugation between Enterobacteriaceae. Our data show that pathogen-driven inflammatory responses in the gut can generate transient enterobacterial blooms in which conjugative transfer occurs at unprecedented rates. These blooms may favor reassortment of plasmid-encoded genes between pathogens and commensals fostering the spread of fitness-, virulence-, and antibiotic-resistance determinants.


Asunto(s)
Evolución Biológica , Colitis/microbiología , Enterobacteriaceae/genética , Transferencia de Gen Horizontal/genética , Animales , Plásmidos de Bacteriocinas/genética , Secuencia de Bases , Biología Computacional , Cartilla de ADN/genética , Enterobacteriaceae/crecimiento & desarrollo , Escherichia coli/genética , Ratones , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Filogenia , ARN Ribosómico 16S/genética , Salmonella typhimurium/genética , Alineación de Secuencia , Análisis de Secuencia de ADN
6.
Proc Natl Acad Sci U S A ; 109(9): 3416-21, 2012 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-22331916

RESUMEN

Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections.


Asunto(s)
Variación Antigénica/genética , Evolución Molecular , Genoma de Protozoos , Evasión Inmune/genética , Trypanosoma brucei brucei/inmunología , Trypanosoma congolense/inmunología , Trypanosoma vivax/inmunología , Glicoproteínas Variantes de Superficie de Trypanosoma/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Protozoario/genética , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Filogenia , Conformación Proteica , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Recombinación Genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Trypanosoma brucei brucei/genética , Trypanosoma congolense/genética , Trypanosoma vivax/genética , Glicoproteínas Variantes de Superficie de Trypanosoma/química , Glicoproteínas Variantes de Superficie de Trypanosoma/inmunología
7.
Nat Methods ; 6(4): 291-5, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19287394

RESUMEN

Amplification artifacts introduced during library preparation for the Illumina Genome Analyzer increase the likelihood that an appreciable proportion of these sequences will be duplicates and cause an uneven distribution of read coverage across the targeted sequencing regions. As a consequence, these unfavorable features result in difficulties in genome assembly and variation analysis from the short reads, particularly when the sequences are from genomes with base compositions at the extremes of high or low G+C content. Here we present an amplification-free method of library preparation, in which the cluster amplification step, rather than the PCR, enriches for fully ligated template strands, reducing the incidence of duplicate sequences, improving read mapping and single nucleotide polymorphism calling and aiding de novo assembly. We illustrate this by generating and analyzing DNA sequences from extremely (G+C)-poor (Plasmodium falciparum), (G+C)-neutral (Escherichia coli) and (G+C)-rich (Bordetella pertussis) genomes.


Asunto(s)
Composición de Base , Mapeo Cromosómico/métodos , Biblioteca de Genes , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , Datos de Secuencia Molecular , Técnicas de Amplificación de Ácido Nucleico
8.
Front Cell Infect Microbiol ; 12: 900084, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35811682

RESUMEN

Visceral leishmaniasis is an important global health problem with an estimated of 50,000 to 90,000 new cases per year. VL is the most serious form of leishmaniasis as it can be fatal in 95% of the cases if it remains untreated. VL is a particularly acute problem in Brazil which contributed with 97% of all cases reported in 2020 in the Americas. In this country, VL affects mainly the poorest people in both urban and rural areas and continues to have a high mortality rate estimated around 8.15%. Here, we performed a temporal parasite population study using whole genome sequence data from a set of 34 canine isolates sampled in 2008, 2012 and 2015 from a re-emergent focus in Southeastern Brazil. Our study found the presence of two distinct sexual subpopulations that corresponded to two isolation periods. These subpopulations diverged hundreds of years ago with no apparent gene flow between them suggesting a process of rapid replacement during a two-year period. Sequence comparisons and analysis of nucleotide diversity also showed evidence of balancing selection acting on transport-related genes and antigenic families. To our knowledge this is the first population genomic study showing a turn-over of parasite populations in an endemic region for leishmaniasis. The complexity and rapid adaptability of these parasites pose new challenges to control activities and demand more integrated approaches to understand this disease in New World foci.


Asunto(s)
Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Leishmaniasis , Animales , Brasil/epidemiología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Perros , Humanos , Leishmania infantum/genética , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/veterinaria
9.
Parasit Vectors ; 14(1): 15, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407867

RESUMEN

BACKGROUND: Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that affects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control require a better understanding of the key step for transmission, namely the establishment of infection inside the fly. METHODS: The aim of this work was to identify sand fly systemic transcriptomic signatures associated with Leishmania infection. We used next generation sequencing to describe the transcriptome of whole Phlebotomus papatasi sand flies when fed with blood alone (control) or with blood containing one of three trypanosomatids: Leishmania major, L. donovani and Herpetomonas muscarum, the latter being a parasite not transmitted to humans. RESULTS: Of the trypanosomatids studied, only L. major was able to successfully establish an infection in the host P. papatasi. However, the transcriptional signatures observed after each parasite-contaminated blood meal were not specific to success or failure of a specific infection and they did not differ from each other. The transcriptional signatures were also indistinguishable after a non-contaminated blood meal. CONCLUSIONS: The results imply that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. Alternatively, Leishmania could suppress host responses. These results will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.


Asunto(s)
Perfilación de la Expresión Génica , Phlebotomus/parasitología , Trypanosomatina , Animales , Sangre/parasitología , Conducta Alimentaria , Humanos , Insectos Vectores/metabolismo , Insectos Vectores/parasitología , Leishmania infantum , Leishmania major , Leishmaniasis/parasitología , Leishmaniasis/transmisión , Phlebotomus/metabolismo
10.
mBio ; 12(3): e0097121, 2021 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-34182785

RESUMEN

Visceral leishmaniasis (VL) is a fatal disease and a growing public health problem in East Africa, where Ethiopia has one of the highest VL burdens. The largest focus of VL in Ethiopia is driven by high prevalence in migrant agricultural workers and associated with a high rate of coinfection with HIV. This coinfection makes VL more difficult to treat successfully and is associated with a high rate of relapse, with VL/HIV patients frequently experiencing many relapses of VL before succumbing to this infection. We present genome-wide data on Leishmania donovani isolates from a longitudinal study of cohorts of VL and VL/HIV patients reporting to a single clinic in Ethiopia. Extensive clinical data allow us to investigate the influence of coinfection and relapse on the populations of parasites infecting these patients. We find that the same parasite population is responsible for both VL and VL/HIV infections and that, in most cases, disease relapse is caused by recrudescence of the population of parasites that caused primary VL. Complex, multiclonal infections are present in both primary and relapse cases, but the infrapopulation of parasites within a patient loses genetic diversity between primary disease presentation and subsequent relapses, presumably due to a population bottleneck induced by treatment. These data suggest that VL/HIV relapses are not caused by genetically distinct parasite infections or by reinfection. Treatment of VL does not lead to sterile cure, and in VL/HIV, the infecting parasites are able to reestablish after clinically successful treatment, leading to repeated relapse of VL. IMPORTANCE Visceral leishmaniasis (VL) is the second largest cause of deaths due to parasite infections and a growing problem in East Africa. In Ethiopia, it is particularly associated with migrant workers moving from regions of nonendemicity for seasonal agricultural work and is frequently found as a coinfection with HIV, which leads to frequent VL relapse following treatment. Insight into the process of relapse in these patients is thus key to controlling the VL epidemic in Ethiopia. We show that there is little genetic differentiation between the parasites infecting HIV-positive and HIV-negative VL patients. Moreover, we provide evidence that relapses are caused by the initially infecting parasite population and that treatment induces a loss of genetic diversity in this population. We propose that restoring functioning immunity and improving antiparasitic treatment may be key in breaking the cycle of relapsing VL in VL/HIV patients.


Asunto(s)
Evolución Molecular , Variación Genética , Infecciones por VIH/parasitología , Interacciones Huésped-Parásitos/genética , Leishmania donovani/genética , Coinfección/complicaciones , Coinfección/epidemiología , Coinfección/parasitología , Coinfección/virología , Etiopía/epidemiología , Infecciones por VIH/epidemiología , Humanos , Leishmania donovani/patogenicidad , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Estudios Longitudinales , Recurrencia , Secuenciación Completa del Genoma
11.
Elife ; 102021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33648633

RESUMEN

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection.


Asunto(s)
Variación Antigénica , Interacciones Huésped-Patógeno/genética , Malaria Falciparum/inmunología , Plasmodium falciparum/genética , Adulto , Animales , Anopheles/parasitología , Anticuerpos Antiprotozoarios/genética , Anticuerpos Antiprotozoarios/metabolismo , Antígenos de Protozoos , Eritrocitos/inmunología , Eritrocitos/parasitología , Femenino , Interacciones Huésped-Patógeno/inmunología , Humanos , Inflamación , Malaria Falciparum/parasitología , Malaria Falciparum/transmisión , Masculino , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo
12.
PLoS Negl Trop Dis ; 14(4): e0007143, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32310945

RESUMEN

Parasites of the genus Leishmania (Kinetoplastida: Trypanosomatidae) cause widespread and devastating human diseases. Visceral leishmaniasis due to Leishmania donovani is endemic in Ethiopia where it has also been responsible for major epidemics. The presence of hybrid genotypes has been widely reported in surveys of natural populations, genetic variation reported in a number of Leishmania species, and the extant capacity for genetic exchange demonstrated in laboratory experiments. However, patterns of recombination and the evolutionary history of admixture that produced these hybrid populations remain unclear. Here, we use whole-genome sequence data to investigate Ethiopian L. donovani isolates previously characterized as hybrids by microsatellite and multi-locus sequencing. To date there is only one previous study on a natural population of Leishmania hybrids based on whole-genome sequences. We propose that these hybrids originate from recombination between two different lineages of Ethiopian L. donovani occurring in the same region. Patterns of inheritance are more complex than previously reported with multiple, apparently independent, origins from similar parents that include backcrossing with parental types. Analysis indicates that hybrids are representative of at least three different histories. Furthermore, isolates were highly polysomic at the level of chromosomes with differences between parasites recovered from a recrudescent infection from a previously treated individual. The results demonstrate that recombination is a significant feature of natural populations and contributes to the growing body of data that shows how recombination, and gene flow, shape natural populations of Leishmania.


Asunto(s)
Quimera , Leishmania donovani/genética , Leishmaniasis Visceral/parasitología , Etiopía , Genotipo , Humanos , Recombinación Genética , Secuenciación Completa del Genoma
13.
PLoS Negl Trop Dis ; 14(5): e0007743, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32374726

RESUMEN

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host-parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.


Asunto(s)
Proteínas del Helminto/genética , Schistosoma mansoni/crecimiento & desarrollo , Schistosoma mansoni/genética , Esquistosomiasis mansoni/parasitología , Animales , Femenino , Proteínas del Helminto/metabolismo , Humanos , Masculino , Ratones , Schistosoma mansoni/metabolismo , Esquistosomiasis mansoni/patología , Transcriptoma
14.
Elife ; 92020 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-32209228

RESUMEN

Protozoan parasites of the Leishmania donovani complex - L. donovani and L. infantum - cause the fatal disease visceral leishmaniasis. We present the first comprehensive genome-wide global study, with 151 cultured field isolates representing most of the geographical distribution. L. donovani isolates separated into five groups that largely coincide with geographical origin but vary greatly in diversity. In contrast, the majority of L. infantum samples fell into one globally-distributed group with little diversity. This picture is complicated by several hybrid lineages. Identified genetic groups vary in heterozygosity and levels of linkage, suggesting different recombination histories. We characterise chromosome-specific patterns of aneuploidy and identified extensive structural variation, including known and suspected drug resistance loci. This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of the Leishmania donovani complex.


Asunto(s)
Variación Genética , Genoma de Protozoos , Leishmania donovani/genética , Aneuploidia , Animales , Variaciones en el Número de Copia de ADN , Resistencia a Medicamentos/genética , Evolución Molecular , Heterocigoto , Polimorfismo de Nucleótido Simple , Selección Genética
15.
Mol Biol Evol ; 25(9): 1877-87, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18550617

RESUMEN

The obligate intracellular bacterium Wolbachia pipientis strain wPip induces cytoplasmic incompatibility (CI), patterns of crossing sterility, in the Culex pipiens group of mosquitoes. The complete sequence is presented of the 1.48-Mbp genome of wPip which encodes 1386 coding sequences (CDSs), representing the first genome sequence of a B-supergroup Wolbachia. Comparisons were made with the smaller genomes of Wolbachia strains wMel of Drosophila melanogaster, an A-supergroup Wolbachia that is also a CI inducer, and wBm, a mutualist of Brugia malayi nematodes that belongs to the D-supergroup of Wolbachia. Despite extensive gene order rearrangement, a core set of Wolbachia genes shared between the 3 genomes can be identified and contrasts with a flexible gene pool where rapid evolution has taken place. There are much more extensive prophage and ankyrin repeat encoding (ANK) gene components of the wPip genome compared with wMel and wBm, and both are likely to be of considerable importance in wPip biology. Five WO-B-like prophage regions are present and contain some genes that are identical or highly similar in multiple prophage copies, whereas other genes are unique, and it is likely that extensive recombination, duplication, and insertion have occurred between copies. A much larger number of genes encode ankyrin repeat (ANK) proteins in wPip, with 60 present compared with 23 in wMel, many of which are within or close to the prophage regions. It is likely that this pattern is partly a result of expansions in the wPip lineage, due for example to gene duplication, but their presence is in some cases more ancient. The wPip genome underlines the considerable evolutionary flexibility of Wolbachia, providing clear evidence for the rapid evolution of ANK-encoding genes and of prophage regions. This host-Wolbachia system, with its complex patterns of sterility induced between populations, now provides an excellent model for unraveling the molecular systems underlying host reproductive manipulation.


Asunto(s)
Culex/microbiología , Evolución Molecular , Genoma Bacteriano , Wolbachia/genética , Animales , Repetición de Anquirina/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , ADN Bacteriano , Drosophila melanogaster/microbiología , Duplicación de Gen , Transferencia de Gen Horizontal , Datos de Secuencia Molecular , Profagos/genética , Simbiosis
16.
Wellcome Open Res ; 4: 193, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32055709

RESUMEN

The var gene family of the human malaria parasite Plasmodium falciparum encode proteins that are crucial determinants of both pathogenesis and immune evasion and are highly polymorphic. Here we have assembled nearly complete var gene repertoires from 2398 field isolates and analysed a normalised set of 714 from across 12 countries. This therefore represents the first large scale attempt to catalogue the worldwide distribution of var gene sequences We confirm the extreme polymorphism of this gene family but also demonstrate an unexpected level of sequence sharing both within and between continents. We show that this is likely due to both the remnants of selective sweeps as well as a worrying degree of recent gene flow across continents with implications for the spread of drug resistance. We also address the evolution of the var repertoire with respect to the ancestral genes within the Laverania and show that diversity generated by recombination is concentrated in a number of hotspots. An analysis of the subdomain structure indicates that some existing definitions may need to be revised From the analysis of this data, we can now understand the way in which the family has evolved and how the diversity is continuously being generated. Finally, we demonstrate that because the genes are distributed across the genome, sequence sharing between genotypes acts as a useful population genetic marker.

17.
BMC Biol ; 5: 39, 2007 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-17883830

RESUMEN

BACKGROUND: Wolbachia are obligate endosymbiotic bacteria maternally transmitted through the egg cytoplasm that are responsible for several reproductive disorders in their insect hosts, such as cytoplasmic incompatibility (CI) in infected mosquitoes. Species in the Culex pipiens complex display an unusually high number of Wolbachia-induced crossing types, and based on present data, only the wPip strain is present. RESULTS: The sequencing of the wPip strain of Wolbachia revealed the presence of 60 ankyrin repeat domain (ANK) encoding genes and expression studies of these genes were carried out in adult mosquitoes. One of these ANK genes, pk2, is shown to be part of an operon of three prophage-associated genes with sex-specific expression, and is present in two identical copies in the genome. Another homolog of pk2 is also present that is differentially expressed in different Cx. pipiens group strains. A further two ANK genes showed sex-specific regulation in wPip-infected Cx. pipiens group adults. CONCLUSION: The high number, variability and differential expression of ANK genes in wPip suggest an important role in Wolbachia biology, and the gene family provides both markers and promising candidates for the study of reproductive manipulation.


Asunto(s)
Repetición de Anquirina , Culex/microbiología , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Wolbachia/genética , Animales , Culex/fisiología , Cartilla de ADN , Interacciones Huésped-Patógeno , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Simbiosis , Wolbachia/fisiología
18.
Elife ; 72018 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-29580379

RESUMEN

Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations but has not yet been widely applied to single-celled organisms. Transcriptional variation in unicellular malaria parasites from the Plasmodium genus is associated with critical phenotypes including red blood cell invasion and immune evasion, yet transcriptional variation at an individual parasite level has not been examined in depth. Here, we describe the adaptation of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute transcriptional variation for more than 500 individual parasites of both rodent and human malaria comprising asexual and sexual life-cycle stages. We uncover previously hidden discrete transcriptional signatures during the pathogenic part of the life cycle, suggesting that expression over development is not as continuous as commonly thought. In transmission stages, we find novel, sex-specific roles for differential expression of contingency gene families that are usually associated with immune evasion and pathogenesis.


Asunto(s)
Perfilación de la Expresión Génica , Variación Genética , Plasmodium/genética , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Animales , Humanos , Roedores
19.
mBio ; 8(5)2017 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-28900023

RESUMEN

Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal "somy" (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection.IMPORTANCELeishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy.


Asunto(s)
Dosificación de Gen , Regulación de la Expresión Génica , Genoma de Protozoos , Leishmania donovani/genética , ADN Protozoario/genética , Genes Protozoarios , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leishmaniasis Cutánea/parasitología , Leishmaniasis Visceral/parasitología , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN
20.
Sci Rep ; 7: 40804, 2017 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-28091623

RESUMEN

Leishmaniasis is a highly diverse group of diseases caused by kinetoplastid of the genus Leishmania. These parasites are taxonomically diverse, with human pathogenic species separated into two subgenera according to their development site inside the alimentary tract of the sand fly insect vector. The disease encompasses a variable spectrum of clinical manifestations with tegumentary or visceral symptoms. Among the causative species in Brazil, Leishmania (Leishmania) amazonensis is an important etiological agent of human cutaneous leishmaniasis that accounts for more than 8% of all cases in endemic regions. L. (L.) amazonensis is generally found in the north and northeast regions of Brazil. Here, we report the first isolation of L. (L.) amazonensis from dogs with clinical manifestations of visceral leishmaniasis in Governador Valadares, an endemic focus in the southeastern Brazilian State of Minas Gerais where L. (L.) infantum is also endemic. These isolates were characterized in terms of SNPs, chromosome and gene copy number variations, confirming that they are closely related to a previously sequenced isolate obtained in 1973 from the typical Northern range of this species. The results presented in this article will increase our knowledge of L. (L.) amazonensis-specific adaptations to infection, parasite survival and the transmission of this Amazonian species in a new endemic area of Brazil.


Asunto(s)
Enfermedades de los Perros/parasitología , Genoma de Protozoos , Leishmania/genética , Leishmaniasis/parasitología , Animales , Brasil , Variaciones en el Número de Copia de ADN , Enfermedades de los Perros/epidemiología , Perros , Leishmania/aislamiento & purificación , Leishmania/patogenicidad , Leishmaniasis/epidemiología , Leishmaniasis/veterinaria , Polimorfismo de Nucleótido Simple
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