The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum.
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ABSTRACT:
SUBMITTER: Neafsey DE
PROVIDER: S-EPMC3432710 | biostudies-literature | 2012 Sep
REPOSITORIES: biostudies-literature
Publications
The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum.
Neafsey Daniel E DE Galinsky Kevin K Jiang Rays H Y RH Young Lauren L Sykes Sean M SM Saif Sakina S Gujja Sharvari S Goldberg Jonathan M JM Young Sarah S Zeng Qiandong Q Chapman Sinéad B SB Dash Aditya P AP Anvikar Anupkumar R AR Sutton Patrick L PL Birren Bruce W BW Escalante Ananias A AA Barnwell John W JW Carlton Jane M JM
Nature genetics 20120805 9
We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a ...[more]
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Project description:BACKGROUND:Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium. Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS). METHODS:Plasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13-2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation. RESULTS:Sequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (? = 0.00036 ± 0.00003), with the highest ? value observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright's fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with FST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations (FST = 0.60266), and between Thailand and Iran populations (FST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes. CONCLUSIONS:The present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV.
| S-EPMC7137254 | biostudies-literature
Project description:BACKGROUND: Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. METHODS: Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. RESULTS AND CONCLUSION: A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n?=?77) for pvama-1; 23 (n?=?84) for pvcsp; and 23 (n?=?35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n?=?30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n?=?11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.
| S-EPMC3519596 | biostudies-literature
Project description:We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.
| S-EPMC1460124 | biostudies-other
Project description:Genetic diversity and population structure of Plasmodium vivax parasites are valuable to the prediction of the origin and spread of novel variants within and between populations, and to the program evaluation of malaria control measures. Using two polymorphic genetic markers, the merozoite surface protein genes PvMSP-3? and PvMSP-3?, we investigated the genetic diversity of four Southeast Asian P. vivax populations, representing both subtropical and temperate strains with dramatically divergent relapse patterns. PCR amplification of PvMSP-3? and PvMSP-3? genes detected three and four major size polymorphisms among the 235 infections examined, respectively, while restriction analysis detected 15 and 19 alleles, respectively. Samples from different geographical areas differed dramatically in their PvMSP-3? and PvMSP-3? allele composition and frequency. Samples tended to cluster on the basis of their PCR-RFLP polymorphism. These results indicated that different parasite genotypes were circulating in each endemic area, and that geographic isolation may exist. Multiple infections were detected in all four parasite populations, ranging from 20.5% to 31.8%, strongly indicating that P. vivax populations were highly diverse and multiple clonal infections are common in these malaria-hypoendemic regions of Southeast Asia.
| S-EPMC3143071 | biostudies-literature
Project description:BACKGROUND:Plasmodium lactate dehydrogenase (pLDH) is a major target in diagnosing the erythrocytic stage of malaria parasites because it is highly expressed during blood-stage parasites and is distinguished from human LDH. Rapid diagnostic tests (RDTs) for malaria use pLDH as a target antigen; however, genetic variations in pLDH within the natural population threaten the efficacy of pLDH-based RDTs. METHODS:Genetic polymorphisms of Plasmodium vivax LDH (PvLDH) and Plasmodium falciparum LDH (PfLDH) in Myanmar isolates were analysed by nucleotide sequencing analysis. Genetic polymorphisms and the natural selection of PvLDH and PfLDH were analysed using DNASTAR, MEGA6, and DnaSP ver. 5.10.00 programs. The genetic diversity and natural selection of global PvLDH and PfLDH were also analysed. The haplotype network of global PvLDH and PfLDH was constructed using NETWORK ver. 5.0.0.3. Three-dimensional structures of PvLDH and PfLDH were built with YASARA Structure ver. 18.4.24 and the impact of mutations on structural change and stability was evaluated with SDM ver. 2, CUPSAT and MAESTROweb. RESULTS:Forty-nine PvLDH and 52 PfLDH sequences were obtained from Myanmar P. vivax and P. falciparum isolates. Non-synonymous nucleotide substitutions resulting in amino acid changes were identified in both Myanmar PvLDH and PfLDH. Amino acid changes were also identified in the global PvLDH and PfLDH populations, but they did not produce structural alterations in either protein. Low genetic diversity was observed in global PvLDH and PfLDH, which may be maintained by a strong purifying selection. CONCLUSION:This study extends knowledge for genetic diversity and natural selection of global PvLDH and PfLDH. Although amino acid changes were observed in global PvLDH and PfLDH, they did not alter the conformational structures of the proteins. These suggest that PvLDH and PfLDH are genetically well-conserved in global populations, which indicates that they are suitable antigens for diagnostic purpose and attractive targets for drug development.
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Project description:Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.
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Project description:We compared transcript levels at several points along the asexual blood cycle between 21 P. falciparum lines. These 21 parasite lines are organized in 4 sets of parasite lines, with all parasite lines within a set sharing a clonal origin. We compared transcript levels within each set. We also performed comparative genome hybridization (CGH) for all 21 parasite lines.
2012-02-07 | E-MTAB-673 | biostudies-arrayexpress
Project description:BackgroundMalaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection.MethodsThis study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated.ResultsThe median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively.ConclusionEarly experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.
| S-EPMC8685492 | biostudies-literature
Project description:Panama and all nations within the Mesoamerican region have committed to eliminate malaria within this decade. With more than 90% of the malaria cases in this region caused by Plasmodium vivax, an efficient national/regional elimination plan must include a comprehensive study of this parasite's genetic diversity. Here, we retrospectively analyzed P. vivax genetic diversity in autochthonous and imported field isolates collected in different endemic regions in Panama from 2007 to 2020, using highly polymorphic markers (csp, msp-1, and msp-3α). We did the analysis using molecular techniques that are cost-effective for malaria molecular surveillance within Mesoamerica. Thus, we used molecular analyses that are feasible for malaria molecular surveillance within the region, and that can provide useful information for policy and decision making about malaria elimination. We also evaluated if haplotypes established by combining the genotypes found in these genes were associated with relevant epidemiological variables and showed structure across the transmission foci that have been observed in Panama. Ten different haplotypes were identified, some of them strongly associated with geographical origin, age, and collection year. Phylogenetic analysis of csp (central repeat domain) revealed that both major variant types (vk210 and vk247) were circulating in Panama. Variant vk247 was restricted to the eastern endemic regions, while vk210 was predominant (77.3%) and widespread, displaying higher diversity (14 alleles) and geographically biased alleles. The regional implications of these molecular findings for the control of P. vivax malaria to achieve elimination across Mesoamerica are discussed.
| S-EPMC8401434 | biostudies-literature
Project description:The malaria parasite Plasmodium falciparum replicates via schizogony: a fundamentally unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. It also has one of the most A/T-biased genomes ever sequenced. Here, we present the first comprehensive study of the specification and activation of DNA replication origins during Plasmodium schizogony. Potential replication origins were found to be abundant, with ORC1-binding sites detected every ~800 bp throughout the genome. They had no motif enrichment, but were biased towards areas of higher G/C content. Origin activation was then measured at single-molecule resolution via DNAscent technology, and was much less dense than ORC1-binding sites, with origins activated preferentially in areas of low transcriptional activity. Consistently, replication forks moved slowest through the most highly transcribed genes, suggesting that conflicts between transcription and origin firing inhibit efficient replication, and that P. falciparum has evolved its S-phase to minimise such conflicts.
2023-01-30 | GSE208757 | GEO