RESUMO
Schistosomiasis, a neglected global pandemic, may be curtailed by blocking transmission of the parasite via its intermediate hosts, aquatic snails. Elucidating the genetic basis of snail-schistosome interaction is a key to this strategy. Here we map a natural parasite-resistance polymorphism from a Caribbean population of the snail Biomphalaria glabrata. In independent experimental evolution lines, RAD genotyping shows that the same genomic region responds to selection for resistance to the parasite Schistosoma mansoni. A dominant allele in this region conveys an 8-fold decrease in the odds of infection. Fine-mapping and RNA-Seq characterization reveal a <1Mb region, the Guadeloupe Resistance Complex (GRC), with 15 coding genes. Seven genes are single-pass transmembrane proteins with putative immunological roles, most of which show strikingly high nonsynonymous divergence (5-10%) among alleles. High linkage disequilibrium among three intermediate-frequency (>25%) haplotypes across the GRC, a significantly non-neutral pattern, suggests that balancing selection maintains diversity at the GRC. Thus, the GRC resembles immune gene complexes seen in other taxa and is likely involved in parasite recognition. The GRC is a potential target for controlling transmission of schistosomiasis, including via genetic manipulation of snails.
Assuntos
Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Caramujos/genética , Caramujos/parasitologia , Animais , Variação Genética , Interações Hospedeiro-Parasita , Humanos , Família Multigênica , Caramujos/imunologia , Índias OcidentaisRESUMO
Antigens present in aqueous n-butanolic extracts (BE) of Schistosoma mansoni (Venezuelan JL strain), Schistosoma intercalatum (Cameroon EDEA strain), and Schistosoma haematobium (Yemen strain) adult worm membranes were compared in immunoblot against sera of patients infected with S. mansoni, S. intercalatum, S. haematobium, Schistosoma japonicum, or Schistosoma mekongi looking for similarities (common antigens) and differences (species-specific antigens). About 17 S. mansoni BE polypeptides (M (r) approximately 8 to >80 kDa) were commonly recognized by S. mansoni-infected patient sera from Venezuela, Senegal, and Ethiopia. S. intercalatum-, S. haematobium-, or S. japonicum-infected sera were almost unreactive with S. mansoni BE. Nonetheless, S. mekongi-infected sera weakly cross-reacted with a approximately 10-15-kDa subset of S. mansoni BE. About 72.7% of S. intercalatum-infected patient sera reacted with a approximately 19-21-kDa complex in S. intercalatum BE and cross-reacted with a similar complex in S. haematobium BE. Conversely, all S. haematobium-infected patient sera reacted with a approximately 19-21-kDa complex in S. haematobium BE and cross-reacted with the approximately 19-21-kDa complex in S. intercalatum BE; S. mansoni- and S. japonicum-infected patient sera did not react with S. intercalatum or S. haematobium BE. Results showed the presence of a common membrane antigen between African schistosome species and species-specific antigens in S. mansoni BE that could be useful to discriminate between species and/or to detect Schistosoma infections.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Schistosoma/imunologia , Esquistossomose/diagnóstico , Esquistossomose/imunologia , Animais , Antígenos de Protozoários/química , Antígenos de Protozoários/isolamento & purificação , Reações Cruzadas , Etiópia , Feminino , Humanos , Immunoblotting/métodos , Masculino , Peso Molecular , Schistosoma/classificação , Senegal , VenezuelaRESUMO
Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.
Assuntos
Variação Genética , Filogenia , Schistosoma mansoni/genética , África , Animais , Arábia , Região do Caribe , DNA de Helmintos/genética , DNA Mitocondrial/genética , Feminino , Geografia , Haplótipos , Humanos , Madagáscar , Masculino , Análise de Sequência de DNA , América do SulRESUMO
Characterizing host and parasite population genetic structure and estimating gene flow among populations is essential for understanding coevolutionary interactions between hosts and parasites. We examined the population genetic structure of the trematode Schistosoma mansoni and its two host species (the definitive host Rattus rattus and the intermediate host Biomphalaria glabrata) using microsatellite markers. Parasites were sampled from rats. The study was conducted in five sites of the Guadeloupe Island, Lesser Antilles. Mollusks display a pattern of isolation by distance whereas such a pattern is not found neither in schistosomes nor in rats. The comparison of the distribution of genetic variability in S. mansoni and its two host species strongly suggests that migration of parasites is principally determined by that of the vertebrate host in the marshy focus of Guadeloupe. However, the comparison between genetic differentiation values in schistosomes and rats suggests that the efficacy of the schistosome rat-mediated dispersal between transmission sites is lower than expected given the prevalence, parasitic load and migration rate of rats among sites. This could notably suggest that rat migration rate could be negatively correlated to the age or the infection status of individuals. Models made about the evolution of local adaptation in function of the dispersal rates of hosts and parasites suggest that rats and mollusks should be locally adapted to their parasites.
Assuntos
Demografia , Variação Genética , Genética Populacional , Ratos/genética , Schistosoma mansoni/genética , Caramujos/genética , Animais , Sequência de Bases , Meio Ambiente , Triagem de Portadores Genéticos , Geografia , Guadalupe , Interações Hospedeiro-Parasita , Repetições de Microssatélites/genética , Modelos Biológicos , Dados de Sequência Molecular , Ratos/parasitologia , Análise de Sequência de DNA , Caramujos/parasitologiaRESUMO
Accurate inferences on population genetics data require a sound underlying theoretical null model. Nearly nothing is known about the gene dynamics of organisms with complex life cycles precluding any biological interpretation of population genetics parameters. In this article, we used an infinite island model to derive the expectations of those parameters for the life cycle of a dioecious organism obligatorily alternating sexual and asexual reproductions as it is the case for schistosomes (plathyhelminth parasites). This model allowed us to investigate the effects of the degree of mixing among individuals coming from different subpopulations at each new generation (represented in the model by the migration rates before and after clonal reproductions) and the variance in the reproductive success of individuals during the clonal phase. We also consider the effects of different migration rates and degrees of clonal reproductive skew between male and female individuals. Results show that the variance in the reproductive success of clones is very important in shaping the distribution of the genetic variability both within and among subpopulations. Thus, higher variance in the reproductive success of clones generates heterozygous excesses within subpopulations and also increases genetic differentiation between them. Migration occurring before and after asexual reproduction has different effects on the patterns of F(IS) and F(ST). When males and females display different degrees of reproductive skew or migration rates, we observe differences in their respective population genetic structure. While results of the model apply to any organism alternating sexual and clonal reproductions (e.g. all parasitic trematodes, many plants, and all aphididae), we finally confront some of these theoretical expectations to empirical data from Schistosoma mansoni infecting Rattus rattus in Guadeloupe.
Assuntos
Variação Genética , Genética Populacional , Modelos Genéticos , Schistosoma/genética , Animais , Feminino , Guadalupe , Masculino , Muridae/parasitologia , Platelmintos/parasitologia , Dinâmica Populacional , Ratos , Reprodução/genética , Fatores SexuaisRESUMO
The mode of reproduction (sexual and/or asexual) and the mating system determine the patterns of gene transmission and genotype formation across generations. Schistosoma mansoni is a dioecious trematode that necessarily alternates sexual and asexual reproduction during its life cycle. In a previous study of the distribution of S. mansoni genetic variability within and between definitive host individuals, we noticed that deleting multilocus genotypes from each infrapopulation so as to keep only one copy of each multilocus genotype, seemed to have a substantial effect on FIS values. More precisely, female FIS increased when repeated genotypes were removed whereas no effect was observed on male FIS. This suggested that multilocus genotypes at high frequency tended to be more heterozygous. The aim of the present study is specifically to test and analyse this phenomenon. We demonstrate that the number of repetitions per clone correlates with individual heterozygosity. This effect is however, sex-specific: only female clone size correlates with heterozygosity. We discuss this phenomenon in relation to the heterozygosity-fitness relationship and the sex-specific response to inbreeding depression.
Assuntos
Variação Genética , Genética Populacional , Schistosoma mansoni/genética , Animais , Simulação por Computador , Feminino , Guadalupe , Heterozigoto , Modelos Lineares , Desequilíbrio de Ligação , Masculino , Repetições de Microssatélites/genética , Método de Monte Carlo , Reprodução/fisiologia , Fatores SexuaisRESUMO
Twelve natural populations of Pseudosuccinea columella snails, sampled in the western and central regions of Cuba, were analyzed using the RAPD-PCR technique to screen for resistance to Fasciola hepatica. Ten OPA primers previously shown to produce marker bands for resistance and susceptibility were tested. A new population of P. columella (El Azufre, Pinar del Río) exhibited the amplification patterns of resistant snails, and its resistant status was confirmed after experimental exposure to miracidia. No genetic variability was detected across or within the susceptible isolates. Similarly, the novel resistant isolate displayed an RAPD profile identical to the profile of two other isolates previously identified as resistant to F. hepatica. However, clear differences in RAPD banding patterns and genetic distance were observed between resistant and susceptible isolates.
Assuntos
Fasciolíase/transmissão , Predisposição Genética para Doença/genética , Lymnaea/genética , Lymnaea/parasitologia , Animais , Cuba , Técnica de Amplificação ao Acaso de DNA PolimórficoRESUMO
Mating system plays a determinant role in the maintenance and distribution of genetic variations. It can be assessed indirectly by analyzing the distribution of the genetic variability within populations or directly by considering how mating pairs are formed. In the present study, 71 pairs of adult Schistosoma mansoni worms sampled from naturally infected rats were genotyped to investigate how male and female schistosomes paired according to their genetic relatedness. Among all samples, pangamy, the random association between males and females, could not be rejected. Whereas the schistosome mating system has been intensively studied under experimental conditions, to the best of our knowledge, our study is the first to attempt to understand the way in which males and females pair in natural conditions.
Assuntos
Variação Genética , Muridae/parasitologia , Doenças dos Roedores/parasitologia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/veterinária , Animais , DNA de Helmintos/química , Feminino , Genótipo , Guadalupe , Heterozigoto , Masculino , Repetições de Microssatélites/genética , Dados de Sequência Molecular , Polimorfismo Genético , Distribuição Aleatória , Reprodução , Schistosoma mansoni/classificação , Schistosoma mansoni/genética , Esquistossomose mansoni/parasitologiaRESUMO
Isolates of Cuban Pseudosuccinea columella susceptible and non-susceptible to Fasciola hepatica miracidial infection were compared for cellular reaction to miracidial development, shell morphometrics, mantle pigmentation pattern, and egg laying behaviour. At 24 h post-exposure, non-susceptible snails showed an early cellular host reaction to encapsulate and phagocytise the miracidium, whereas viable transforming miracidia were observed in exposed susceptible snails, indicating that non-susceptibility resulted from resistance rather than physiological unsuitability. Susceptible isolates (more than 80% susceptible to infection) showed significantly higher values of the morphometric indices shell width/length and aperture width/length than resistant isolates (100% resistant). Mantle pigmentation pattern was analysed using Visilog software; the cumulative distances between mantle spots were plotted and compared between isolates, showing a clear distinction between groups. Egg-laying behaviour also showed significant differences with susceptible snails preferring to lay their eggs on the container's walls whereas resistant snails preferred to lay their eggs on the bottom of the container.
Assuntos
Fasciola hepatica , Caramujos/parasitologia , Animais , Cuba , Interações Hospedeiro-Parasita , Estágios do Ciclo de Vida , Óvulo/crescimento & desenvolvimento , Fenótipo , Caramujos/anatomia & histologia , Caramujos/crescimento & desenvolvimentoRESUMO
Protein electrophoresis, RAPD-PCR and nuclear rDNA ITS sequencing were performed to search for genetic differences between Pseudosuccinea columella snails susceptible and resistant to Fasciola hepatica infection. Of the 21 enzymatic loci analyzed in both populations, none of them exhibited neither within- or between-group variation. Such an absence of enzyme polymorphism support the hypothesis of selfing as the "prevalent" mating system for this hermaphroditic species. Conversely, the RAPD profiles displayed clear differences between susceptible and resistant isolates for 17 of the 26 primers tested while no within-group variation was detected. rDNA ITS sequence analysis from snails of each isolates showed only two bases that differed between groups accounting for a 0.17% of variation confirming that susceptible and resistant snails belong to the same species. This is the first time that a genetic variation using RAPD markers is demonstrated between susceptible and resistant lymnaeid snails vis-a-vis of F. hepatica infection in absence of experimental selection.
Assuntos
Fasciola hepatica/fisiologia , Marcadores Genéticos , Caramujos/genética , Animais , Sequência de Bases , DNA Ribossômico/química , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Isoenzimas/análise , Dados de Sequência Molecular , Técnica de Amplificação ao Acaso de DNA Polimórfico , Caramujos/imunologia , Caramujos/parasitologiaRESUMO
An uncommon snail-trematode interaction pattern was found for the Pseudosuccinea columella - Fasciola hepaticamodel under laboratory conditions. Week-old juveniles from two isolates showed very high rates of infection (90.0% and 93.3%) after exposure to five miracidia. They also showed differences in their life history traits when compared to a control group. However, they did not exhibit the increase in size and reduction/cessation in host fecundity which is usually observed in most of the other related snail-trematode systems. In contrast, infected juvenile P. columella showed increased egg laying after the onset of cercarial emission and there was no effect on growth. A third isolate of P. columella was found to be refractory to miracidial infection. This constitutes the first report of non-susceptibility to F. hepatica in a lymnaeid species which is usually susceptible. These non-susceptible snails exhibited lower fecundity and survival compared to non-exposed susceptible snails under identical laboratory conditions. The differences observed in terms of life span and reproduction could result from the cost of resistance for individuals from this isolate.