Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest.
Circumsporozoite protein (CSP) is the primary pre-erythrocytic vaccine target in Plasmodium species. Knowledge about their genetic diversity can help predict vaccine efficacy and the spread of novel parasite variants. Thus, we investigated pvcsp gene polymorphisms in 219 isolates (136 from Brazilian...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0241426 |
| _version_ | 1828286939558576128 |
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| author | Natália Ketrin Almeida-de-Oliveira Rebecca de Abreu-Fernandes Lidiane Lima-Cury Aline Rosa de Lavigne Anielle de Pina-Costa Daiana de Souza Perce-da-Silva Marcos Catanho Atila Duque Rossi Patrícia Brasil Cláudio Tadeu Daniel-Ribeiro Maria de Fátima Ferreira-da-Cruz |
| author_facet | Natália Ketrin Almeida-de-Oliveira Rebecca de Abreu-Fernandes Lidiane Lima-Cury Aline Rosa de Lavigne Anielle de Pina-Costa Daiana de Souza Perce-da-Silva Marcos Catanho Atila Duque Rossi Patrícia Brasil Cláudio Tadeu Daniel-Ribeiro Maria de Fátima Ferreira-da-Cruz |
| author_sort | Natália Ketrin Almeida-de-Oliveira |
| collection | DOAJ |
| description | Circumsporozoite protein (CSP) is the primary pre-erythrocytic vaccine target in Plasmodium species. Knowledge about their genetic diversity can help predict vaccine efficacy and the spread of novel parasite variants. Thus, we investigated pvcsp gene polymorphisms in 219 isolates (136 from Brazilian Amazon [BA], 71 from Rio de Janeiro Atlantic Forest [AF], and 12 from non-Brazilian countries [NB]). Forty-eight polymorphic sites were detected, 46 in the central repeat region (CR), and two in the C-terminal region. Also, the CR presents InDels and a variable number of repeats. All samples correspond to the VK210 variant, and 24 VK210 subtypes based on CR. Nucleotide diversity (π = 0.0135) generated a significant number of haplotypes (168) with low genetic differentiation between the Brazilian regions (Fst = 0.208). The haplotype network revealed similar distances among the BA and AF regions. The linkage disequilibrium indicates that recombination does not seem to be acting in diversity, reinforcing natural selection's role in accelerating adaptive evolution. The high diversity (low Fst) and polymorphism frequencies could be indicators of balancing selection. Although malaria in BA and AF have distinct vector species and different host immune pressures, consistent genetic signature was found in two regions. The immunodominant B-cell epitope mapped in the CR varies from seven to 19 repeats. The CR T-cell epitope is conserved only in 39 samples. Concerning to C-terminal region, the Th2R epitope presented nonsynonymous SNP only in 6% of Brazilian samples, and the Th3R epitope remained conserved in all studied regions. We conclude that, although the uneven distribution of alleles may jeopardize the deployment of vaccines directed to a specific variable locus, a unique vaccine formulation could protect populations in all Brazilian regions. |
| first_indexed | 2024-04-13T09:40:25Z |
| format | Article |
| id | doaj.art-d9178c7ff83a4f8eb007bbc1b30662c5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T09:40:25Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d9178c7ff83a4f8eb007bbc1b30662c52022-12-22T02:51:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011511e024142610.1371/journal.pone.0241426Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest.Natália Ketrin Almeida-de-OliveiraRebecca de Abreu-FernandesLidiane Lima-CuryAline Rosa de LavigneAnielle de Pina-CostaDaiana de Souza Perce-da-SilvaMarcos CatanhoAtila Duque RossiPatrícia BrasilCláudio Tadeu Daniel-RibeiroMaria de Fátima Ferreira-da-CruzCircumsporozoite protein (CSP) is the primary pre-erythrocytic vaccine target in Plasmodium species. Knowledge about their genetic diversity can help predict vaccine efficacy and the spread of novel parasite variants. Thus, we investigated pvcsp gene polymorphisms in 219 isolates (136 from Brazilian Amazon [BA], 71 from Rio de Janeiro Atlantic Forest [AF], and 12 from non-Brazilian countries [NB]). Forty-eight polymorphic sites were detected, 46 in the central repeat region (CR), and two in the C-terminal region. Also, the CR presents InDels and a variable number of repeats. All samples correspond to the VK210 variant, and 24 VK210 subtypes based on CR. Nucleotide diversity (π = 0.0135) generated a significant number of haplotypes (168) with low genetic differentiation between the Brazilian regions (Fst = 0.208). The haplotype network revealed similar distances among the BA and AF regions. The linkage disequilibrium indicates that recombination does not seem to be acting in diversity, reinforcing natural selection's role in accelerating adaptive evolution. The high diversity (low Fst) and polymorphism frequencies could be indicators of balancing selection. Although malaria in BA and AF have distinct vector species and different host immune pressures, consistent genetic signature was found in two regions. The immunodominant B-cell epitope mapped in the CR varies from seven to 19 repeats. The CR T-cell epitope is conserved only in 39 samples. Concerning to C-terminal region, the Th2R epitope presented nonsynonymous SNP only in 6% of Brazilian samples, and the Th3R epitope remained conserved in all studied regions. We conclude that, although the uneven distribution of alleles may jeopardize the deployment of vaccines directed to a specific variable locus, a unique vaccine formulation could protect populations in all Brazilian regions.https://doi.org/10.1371/journal.pone.0241426 |
| spellingShingle | Natália Ketrin Almeida-de-Oliveira Rebecca de Abreu-Fernandes Lidiane Lima-Cury Aline Rosa de Lavigne Anielle de Pina-Costa Daiana de Souza Perce-da-Silva Marcos Catanho Atila Duque Rossi Patrícia Brasil Cláudio Tadeu Daniel-Ribeiro Maria de Fátima Ferreira-da-Cruz Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. PLoS ONE |
| title | Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. |
| title_full | Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. |
| title_fullStr | Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. |
| title_full_unstemmed | Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. |
| title_short | Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest. |
| title_sort | balancing selection and high genetic diversity of plasmodium vivax circumsporozoite central region in parasites from brazilian amazon and rio de janeiro atlantic forest |
| url | https://doi.org/10.1371/journal.pone.0241426 |
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