Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya
Background: Malaria elimination and eradication efforts can be advanced by including transmission-blocking or reducing vaccines (TBVs) alongside existing interventions. Key transmission-blocking vaccine candidates, such as Pfs230 domain one and Pfs48/45 domain 3, should be genetically stable to avoi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.867906/full |
| _version_ | 1818009017028444160 |
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| author | Kevin O. Ochwedo Kevin O. Ochwedo Fredrick O. Ariri Fredrick O. Ariri Wilfred O. Otambo Wilfred O. Otambo Edwin O. Magomere Edwin O. Magomere Isaiah Debrah Isaiah Debrah Shirley A. Onyango Shirley A. Onyango Pauline W. Orondo Harrysone E. Atieli Sidney O. Ogolla Antony C. A. Otieno Wolfgang R. Mukabana Wolfgang R. Mukabana Andrew K. Githeko Andrew K. Githeko Ming-Chieh Lee Guiyun Yan Daibin Zhong James W. Kazura |
| author_facet | Kevin O. Ochwedo Kevin O. Ochwedo Fredrick O. Ariri Fredrick O. Ariri Wilfred O. Otambo Wilfred O. Otambo Edwin O. Magomere Edwin O. Magomere Isaiah Debrah Isaiah Debrah Shirley A. Onyango Shirley A. Onyango Pauline W. Orondo Harrysone E. Atieli Sidney O. Ogolla Antony C. A. Otieno Wolfgang R. Mukabana Wolfgang R. Mukabana Andrew K. Githeko Andrew K. Githeko Ming-Chieh Lee Guiyun Yan Daibin Zhong James W. Kazura |
| author_sort | Kevin O. Ochwedo |
| collection | DOAJ |
| description | Background: Malaria elimination and eradication efforts can be advanced by including transmission-blocking or reducing vaccines (TBVs) alongside existing interventions. Key transmission-blocking vaccine candidates, such as Pfs230 domain one and Pfs48/45 domain 3, should be genetically stable to avoid developing ineffective vaccines due to antigenic polymorphisms. We evaluated genetic polymorphism and temporal stability of Pfs230 domain one and Pfs48/45 domain three in Plasmodium falciparum parasites from western Kenya.Methods: Dry blood spots on filter paper were collected from febrile malaria patients reporting to community health facilities in endemic areas of Homa Bay and Kisumu Counties and an epidemic-prone area of Kisii County in 2018 and 2019. Plasmodium speciation was performed using eluted DNA and real-time PCR. Amplification of the target domains of the two Pfs genes was performed on P. falciparum positive samples. We sequenced Pfs230 domain one on 156 clinical isolates and Pfs48/45 domain three on 118 clinical isolates to infer the levels of genetic variability, signatures of selection, genetic diversity indices and perform other evolutionary analyses.Results:Pfs230 domain one had low nucleotide diversity (π = 0.15 × 10–2) with slight variation per study site. Six polymorphic sites with nonsynonymous mutations and eight haplotypes were discovered. I539T was a novel variant, whereas G605S was nearing fixation. Pfs48/45 domain three had a low π (0.063 × 10–2), high conservation index, and three segregating sites, resulting in nonsynonymous mutation and four haplotypes. Some loci of Pfs230 D1 were in positive or negative linkage disequilibrium, had negative or positive selection signatures, and others (1813, 1955) and (1813, 1983) had a history of recombination. Mutated loci pairs in Pfs48/45 domain three had negative linkage disequilibrium, and some had negative and positive Tajima’s D values with no history of recombination events.Conclusion: The two transmission blocking vaccine candidates have low nucleotide diversity, a small number of zone-specific variants, high nucleotide conservation index, and high frequency of rare alleles. With the near fixation a polymorphic site and the proximity of mutated codons to antibody binding epitopes, it will be necessary to continue monitoring sequence modifications of these domains when designing TBVs that include Pfs230 and Pfs48/45 antigens. |
| first_indexed | 2024-04-14T05:37:28Z |
| format | Article |
| id | doaj.art-7d1ad5e18b954fb0a0e007f436860ec7 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T05:37:28Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-7d1ad5e18b954fb0a0e007f436860ec72022-12-22T02:09:35ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-05-011310.3389/fgene.2022.867906867906Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western KenyaKevin O. Ochwedo0Kevin O. Ochwedo1Fredrick O. Ariri2Fredrick O. Ariri3Wilfred O. Otambo4Wilfred O. Otambo5Edwin O. Magomere6Edwin O. Magomere7Isaiah Debrah8Isaiah Debrah9Shirley A. Onyango10Shirley A. Onyango11Pauline W. Orondo12Harrysone E. Atieli13Sidney O. Ogolla14Antony C. A. Otieno15Wolfgang R. Mukabana16Wolfgang R. Mukabana17Andrew K. Githeko18Andrew K. Githeko19Ming-Chieh Lee20Guiyun Yan21Daibin Zhong22James W. Kazura23Department of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaDepartment of Zoology, School of Physical and Biological Sciences, Maseno University, Kisumu, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaDepartment of Zoology, School of Physical and Biological Sciences, Maseno University, Kisumu, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaDepartment of Biochemistry, Egerton University, Nakuru, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaWest Africa Centre for Cell Biology of Infectious Pathogen, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, GhanaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaSchool of Zoological Sciences, Kenyatta University, Nairobi, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaCentre for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, KenyaDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, KenyaCentre for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, CA, United StatesProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, CA, United StatesProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, CA, United StatesCentre for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, United StatesBackground: Malaria elimination and eradication efforts can be advanced by including transmission-blocking or reducing vaccines (TBVs) alongside existing interventions. Key transmission-blocking vaccine candidates, such as Pfs230 domain one and Pfs48/45 domain 3, should be genetically stable to avoid developing ineffective vaccines due to antigenic polymorphisms. We evaluated genetic polymorphism and temporal stability of Pfs230 domain one and Pfs48/45 domain three in Plasmodium falciparum parasites from western Kenya.Methods: Dry blood spots on filter paper were collected from febrile malaria patients reporting to community health facilities in endemic areas of Homa Bay and Kisumu Counties and an epidemic-prone area of Kisii County in 2018 and 2019. Plasmodium speciation was performed using eluted DNA and real-time PCR. Amplification of the target domains of the two Pfs genes was performed on P. falciparum positive samples. We sequenced Pfs230 domain one on 156 clinical isolates and Pfs48/45 domain three on 118 clinical isolates to infer the levels of genetic variability, signatures of selection, genetic diversity indices and perform other evolutionary analyses.Results:Pfs230 domain one had low nucleotide diversity (π = 0.15 × 10–2) with slight variation per study site. Six polymorphic sites with nonsynonymous mutations and eight haplotypes were discovered. I539T was a novel variant, whereas G605S was nearing fixation. Pfs48/45 domain three had a low π (0.063 × 10–2), high conservation index, and three segregating sites, resulting in nonsynonymous mutation and four haplotypes. Some loci of Pfs230 D1 were in positive or negative linkage disequilibrium, had negative or positive selection signatures, and others (1813, 1955) and (1813, 1983) had a history of recombination. Mutated loci pairs in Pfs48/45 domain three had negative linkage disequilibrium, and some had negative and positive Tajima’s D values with no history of recombination events.Conclusion: The two transmission blocking vaccine candidates have low nucleotide diversity, a small number of zone-specific variants, high nucleotide conservation index, and high frequency of rare alleles. With the near fixation a polymorphic site and the proximity of mutated codons to antibody binding epitopes, it will be necessary to continue monitoring sequence modifications of these domains when designing TBVs that include Pfs230 and Pfs48/45 antigens.https://www.frontiersin.org/articles/10.3389/fgene.2022.867906/fullPfs230Pfs48/45transmission blocking vaccinesgenetic diversityevolutionary forces |
| spellingShingle | Kevin O. Ochwedo Kevin O. Ochwedo Fredrick O. Ariri Fredrick O. Ariri Wilfred O. Otambo Wilfred O. Otambo Edwin O. Magomere Edwin O. Magomere Isaiah Debrah Isaiah Debrah Shirley A. Onyango Shirley A. Onyango Pauline W. Orondo Harrysone E. Atieli Sidney O. Ogolla Antony C. A. Otieno Wolfgang R. Mukabana Wolfgang R. Mukabana Andrew K. Githeko Andrew K. Githeko Ming-Chieh Lee Guiyun Yan Daibin Zhong James W. Kazura Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya Frontiers in Genetics Pfs230 Pfs48/45 transmission blocking vaccines genetic diversity evolutionary forces |
| title | Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya |
| title_full | Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya |
| title_fullStr | Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya |
| title_full_unstemmed | Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya |
| title_short | Rare Alleles and Signatures of Selection on the Immunodominant Domains of Pfs230 and Pfs48/45 in Malaria Parasites From Western Kenya |
| title_sort | rare alleles and signatures of selection on the immunodominant domains of pfs230 and pfs48 45 in malaria parasites from western kenya |
| topic | Pfs230 Pfs48/45 transmission blocking vaccines genetic diversity evolutionary forces |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.867906/full |
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