Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum
Abstract Background The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Parasites & Vectors |
| Online Access: | http://link.springer.com/article/10.1186/s13071-017-2260-z |
| _version_ | 1818215860461895680 |
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| author | Kolapo M. Oyebola Emmanuel T. Idowu Yetunde A. Olukosi Taiwo S. Awolola Alfred Amambua-Ngwa |
| author_facet | Kolapo M. Oyebola Emmanuel T. Idowu Yetunde A. Olukosi Taiwo S. Awolola Alfred Amambua-Ngwa |
| author_sort | Kolapo M. Oyebola |
| collection | DOAJ |
| description | Abstract Background The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. Methods We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima’s D) and integrated haplotype score (iHS) to identify genes under selection. Results Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima’s D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. Conclusion We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known genomic signatures of selection from drug pressure and host immunity. This is evidence that P. falciparum populations explore common adaptive strategies that can be targeted for the development of new interventions. |
| first_indexed | 2024-12-12T06:42:47Z |
| format | Article |
| id | doaj.art-03de2cf2af1f443da484cff2ce78dedf |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-12T06:42:47Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-03de2cf2af1f443da484cff2ce78dedf2022-12-22T00:34:17ZengBMCParasites & Vectors1756-33052017-06-011011710.1186/s13071-017-2260-zPooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparumKolapo M. Oyebola0Emmanuel T. Idowu1Yetunde A. Olukosi2Taiwo S. Awolola3Alfred Amambua-Ngwa4Medical Research Council Unit The GambiaParasitology and Bioinformatics, Department of Zoology, Faculty of Science, University of LagosNigerian Institute of Medical ResearchNigerian Institute of Medical ResearchMedical Research Council Unit The GambiaAbstract Background The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. Methods We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima’s D) and integrated haplotype score (iHS) to identify genes under selection. Results Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima’s D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. Conclusion We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known genomic signatures of selection from drug pressure and host immunity. This is evidence that P. falciparum populations explore common adaptive strategies that can be targeted for the development of new interventions.http://link.springer.com/article/10.1186/s13071-017-2260-z |
| spellingShingle | Kolapo M. Oyebola Emmanuel T. Idowu Yetunde A. Olukosi Taiwo S. Awolola Alfred Amambua-Ngwa Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum Parasites & Vectors |
| title | Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum |
| title_full | Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum |
| title_fullStr | Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum |
| title_full_unstemmed | Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum |
| title_short | Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum |
| title_sort | pooled dna sequencing identifies genomic regions of selection in nigerian isolates of plasmodium falciparum |
| url | http://link.springer.com/article/10.1186/s13071-017-2260-z |
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