Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali
Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.943445/full |
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| author | Aoua Coulibaly Aoua Coulibaly Mouhamadou Fadel Diop Aminatou Kone Antoine Dara Amed Ouattara Amed Ouattara Nicola Mulder Olivo Miotto Mahamadou Diakite Abdoulaye Djimde Alfred Amambua-Ngwa |
| author_facet | Aoua Coulibaly Aoua Coulibaly Mouhamadou Fadel Diop Aminatou Kone Antoine Dara Amed Ouattara Amed Ouattara Nicola Mulder Olivo Miotto Mahamadou Diakite Abdoulaye Djimde Alfred Amambua-Ngwa |
| author_sort | Aoua Coulibaly |
| collection | DOAJ |
| description | Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented. |
| first_indexed | 2024-04-12T03:31:25Z |
| format | Article |
| id | doaj.art-b410892a4b84462dad8c61c30bc4aa50 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T03:31:25Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b410892a4b84462dad8c61c30bc4aa502022-12-22T03:49:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-10-011310.3389/fgene.2022.943445943445Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern MaliAoua Coulibaly0Aoua Coulibaly1Mouhamadou Fadel Diop2Aminatou Kone3Antoine Dara4Amed Ouattara5Amed Ouattara6Nicola Mulder7Olivo Miotto8Mahamadou Diakite9Abdoulaye Djimde10Alfred Amambua-Ngwa11Malaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliComputational Biology Division, University of Cape Town, Cape Town, South AfricaDisease Control and Elimination, Medical Research Council Unit The Gambia at LSHTM, Banjul, GambiaMalaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliMalaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliMalaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliUniversity of Maryland Baltimore, Baltimore, MD, United StatesComputational Biology Division, University of Cape Town, Cape Town, South AfricaMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, ThailandMalaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliMalaria Research and Training Center, University of Science, Techniques, and Technologies of Bamako, Bamako, MaliDisease Control and Elimination, Medical Research Council Unit The Gambia at LSHTM, Banjul, GambiaPlasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented.https://www.frontiersin.org/articles/10.3389/fgene.2022.943445/fullmalariadrug resistancegenetic variationpositive selectiondifferentiation |
| spellingShingle | Aoua Coulibaly Aoua Coulibaly Mouhamadou Fadel Diop Aminatou Kone Antoine Dara Amed Ouattara Amed Ouattara Nicola Mulder Olivo Miotto Mahamadou Diakite Abdoulaye Djimde Alfred Amambua-Ngwa Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali Frontiers in Genetics malaria drug resistance genetic variation positive selection differentiation |
| title | Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali |
| title_full | Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali |
| title_fullStr | Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali |
| title_full_unstemmed | Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali |
| title_short | Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali |
| title_sort | genome wide snp analysis of plasmodium falciparum shows differentiation at drug resistance associated loci among malaria transmission settings in southern mali |
| topic | malaria drug resistance genetic variation positive selection differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.943445/full |
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