Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global ...health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole-genome data from eight field samples from a region in Cordóba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•The array containing MSP3 genes was characterized among Plasmodium species.•The P. falciparum MSP3 proteins are analogous to those found in P. vivax.•The high number of paralogs has ...an earlier origin in the P. vivax clade.•Host range cannot explain the variation in the number of paralogs among species.•The MSP3 evolution is consistent with a multi-allelic diversifying selection model.
The genus Plasmodium is a diversified group of parasites with more than 200 known species that includes those causing malaria in humans. These parasites use numerous proteins in a complex process that allows them to invade the red blood cells of their vertebrate hosts. Many of those proteins are part of multi-gene families; one of which is the merozoite surface protein-3 (msp3) family. The msp3 multi-gene family is considered important in the two main human parasites, Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously expressed in the blood stage (merozoite) and are immunogenic. There are large differences among Plasmodium species in the number of paralogs in this family. Such differences have been previously explained, in part, as adaptations that allow the different Plasmodium species to invade their hosts. To investigate this, we characterized the array containing msp3 genes among several Plasmodium species, including P. falciparum and P. vivax. We first found no evidence indicating that the msp3 family of P. falciparum was homologous to that of P. vivax. Subsequently, by focusing on the diverse clade of nonhuman primate parasites to which P. vivax is closely related, where homology was evident, we found no evidence indicating that the interspecies variation in the number of paralogs was an adaptation related to changes in host range or host switches. Overall, we hypothesize that the evolution of the msp3 family in P. vivax is consistent with a model of multi-allelic diversifying selection where the paralogs may have functionally redundant roles in terms of increasing antigenic diversity. Thus, we suggest that the expressed MSP3 proteins could serve as “decoys”, via antigenic diversity, during the critical process of invading the host red blood cells.
Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete ...surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria parasites (genus Plasmodium) are a diverse group found in many species of vertebrate hosts. These parasites invade red blood cells in a complex process comprising several proteins, many ...encoded by multigene families, one of which is merozoite surface protein 7 (msp7). In the case of Plasmodium vivax, the most geographically widespread human-infecting species, differences in the number of paralogs within multigene families have been previously explained, at least in part, as potential adaptations to the human host. To explore this in msp7, we studied its orthologs in closely related nonhuman primate parasites; investigating both paralog evolutionary history and genetic polymorphism. The emerging patterns were then compared with the human parasite Plasmodium falciparum. We found that the evolution of the msp7 family is consistent with a birth-and-death model, where duplications, pseudogenizations, and gene loss events are common. However, all paralogs in P. vivax and P. falciparum had orthologs in their closely related species in non-human primates indicating that the ancestors of those paralogs precede the events leading to their origins as human parasites. Thus, the number of paralogs cannot be explained as an adaptation to human hosts. Although there is no functional information for msp7 in P. vivax, we found evidence for purifying selection in the genetic polymorphism of some of its paralogs as well as their orthologs in closely related non-human primate parasites. We also found evidence indicating that a few of P. vivax's paralogs may have diverged from their orthologs in non-human primates by episodic positive selection. Hence, they may had been under selection when the lineage leading to P. vivax diverged from the Asian non-human primates and switched into Homininae. All these lines of evidence suggest that msp7 is functionally important in P. vivax.
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•The array containing msp7 genes is characterized among Plasmodium species.•The number of msp7 paralogs is particularly high in the P. vivax clade.•The msp7 paralogs in P. vivax and P. falciparum predates their origins as human parasites.•Few Pvmsp7 paralogs may have diverged from their orthologs in non-human primates by episodic positive selection.•Some level of conservation of the HABP peptides across Pfmsp7 and Prmsp7 paralogs was observed.
Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria ...transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods.
A descriptive study that combines active (ACD), passive (PCD), and reactive (RCD) case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604) and 9% by quantitative polymerase chain reaction (qPCR) (52/604) were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence). Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93), most of them being asymptomatic (46/71). Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2%) and An. Darlingi (42,5%). One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA.
This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that lead to discovery of secondary but genetically unrelated malaria cases indicating undetected malaria transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mutations in the
(
) gene are linked to delayed parasite clearance in response to artemisinin-based combination therapies (ACTs) in Southeast Asia. To explore the evolutionary rate and constraints ...acting on this gene,
orthologs from species sharing a recent common ancestor with
and
were analyzed. These comparative studies were followed by genetic polymorphism analyses within
using 982 complete
sequences from public databases and new data obtained by next-generation sequencing from African and Haitian isolates. Although
orthologs evolve at heterogeneous rates, the gene was conserved across the genus, with only synonymous substitutions being found at residues where mutations linked to the delayed parasite clearance phenotype have been reported. This suggests that those residues were under constraint from undergoing nonsynonymous changes during evolution of the genus. No fixed nonsynonymous differences were found between
and its orthologs in closely related species found in African apes. This indicates that all nonsynonymous substitutions currently found in
are younger than the time of divergence between
and its closely related species. At the population level, no mutations linked to delayed parasite clearance were found in our samples from Africa and Haiti. However, there is a high number of single
mutations segregating in
populations, and two predominant alleles are distributed worldwide. This pattern is discussed in terms of how changes in the efficacy of natural selection, affected by population expansion, may have allowed for the emergence of mutations tolerant to ACTs.
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•Plasmodium lineages found in lemurs are a diverse monophyletic group.•Plasmodium in lemurs shares a common ancestor with primate parasites from Africa.•The combination of Apicoplast ...loci with the mtDNA yields robust phylogenies.•There could be co-speciation between Plasmodium parasites and their lemur hosts.•The Plasmodium falciparum clade may have originated with Homininae.
Among the primate malaria parasites, those found in lemurs have been neglected. Here, six Plasmodium lineages were detected in 169 lemurs. Nearly complete mitochondrial genomes (mtDNA, ≈6Kb) and apicoplast loci (≈6Kb) were obtained from these parasites and other Haemosporida species. Plasmodium spp. in lemurs are a diverse clade that shares a common ancestor with other primate parasites from continental Africa. Time-trees for the mtDNA were estimated under different scenarios, and the origin of the lemur clade coincides with the proposed time of their host species' most recent common ancestor (Lemuridae-Indriidae). A time tree with fewer taxa was estimated with mtDNA + Apicoplast loci. Those time estimates overlapped but were younger and had narrower credibility intervals than those from mtDNA alone. Importantly, the mtDNA + Apicoplast estimates that the clade including the most lethal malaria parasite in humans, Plasmodium falciparum, may have originated with Homininae (African apes). Finally, the phylogenetic congruence of the lemurs and their parasites was explored. A statistically significant scenario identified four cospeciation, two duplications, four transfer (host-switches), and zero loss events. Thus, the parasite species sampled in lemurs seem to be radiating with their hosts.
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•The first complete Haemoproteus (subgenus Haemoproteus) apicoplast genome was assembled and annotated.•This genome shares a common conserved structure with other haemosporidian ...apicoplasts.•There is codon usage bias in the haemosporidian apicoplast genome.•Single apicoplast gene phylogenies fail to solve clades that recently diverged.
Apicomplexa is a phylum of parasitic protozoa; among them are the order Haemosporida, vector-borne parasites that include those that cause malaria (genus Plasmodium). Most Apicomplexa species have a non-photosynthetic plastid or apicoplast. Given its unique metabolic pathways, this organelle is considered a target for malaria therapeutics. Regardless of its importance, there is a paucity of complete apicoplast genome data hindering comparative studies. Here, the Haemoproteus (Haemoproteus) columbae apicoplast genome (lineage HAECOL1) was obtained using next-generation sequencing. This genome was included in a comparative analysis with other plastids. This 29.8 kb circular genome shares the same structure found in Plasmodium parasites. It is A + T rich (87.7%), comparable but at the higher end of A + T content observed in Plasmodium species (85.5–87.2%). As expected, considering its high A + T content, the synonymous codon usage (RSCU) and the effective number of codons (ENc) showed a moderate codon bias. Several apicoplast genes have a phylogenetic signal. However, unlike mitochondrial genes, single-gene phylogenies have low support in haemosporidian clades that diverged recently. The H. columbae apicoplast genome suggests that the apicoplast function may be conserved across Haemosporida. This parasite could be a model to study this organelle in a non-mammalian system.
Habitat modification may facilitate the emergence of novel pathogens, and the expansion of agricultural frontiers make domestic animals important sources of pathogen spillover to wild animals. We ...demonstrate for the first time that Plasmodium juxtanucleare, a widespread parasite from domestic chickens, naturally infects free-living passerines. We sampled 68 wild birds within and at the border of conservation units in central Brazil composed by Cerrado, a highly threatened biome. Seven out of 10 passerines captured in the limits of a protected area with a small farm were infected by P. juxtanucleare as was confirmed by sequencing a fragment of the parasite's cytochrome b. Blood smears from these positive passerines presented trophozoites, meronts and gametocytes compatible with P. juxtanucleare, meaning these birds are competent hosts for this parasite. After these intriguing results, we sampled 30 backyard chickens managed at the area where P. juxtanucleare-infected passerines were captured, revealing one chicken infected by the same parasite lineage. We sequenced the almost complete mitochondrial genome from all positive passerines, revealing that Brazilian and Asian parasites are closely related. P. juxtanucleare can be lethal to non-domestic hosts under captive and rehabilitation conditions, suggesting that this novel spillover may pose a real threat to wild birds.
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