Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia
Background. Malaria is still a public health problem in Saudi Arabia specifically in the Jazan region. Plasmodium falciparum knob-associated histidine-rich proteins (PfKAHRPs) play an important role in cerebral malaria pathophysiology as well as pathogenesis of P. falciparum infections. The repeat r...
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Wiley
2022-01-01
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| Series: | Journal of Tropical Medicine |
| Online Access: | http://dx.doi.org/10.1155/2022/3740889 |
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| author | Saad M. Bin Dajem Md Atique Ahmed Marie Fe F Bohol Syeda Wasfeea Wazid Mohammed I. Shafeai Fuad H. Rudiny Ali M. Motaen Kareem Morsy Hani Alothaid Ahmed A. Al-Qahtani |
| author_facet | Saad M. Bin Dajem Md Atique Ahmed Marie Fe F Bohol Syeda Wasfeea Wazid Mohammed I. Shafeai Fuad H. Rudiny Ali M. Motaen Kareem Morsy Hani Alothaid Ahmed A. Al-Qahtani |
| author_sort | Saad M. Bin Dajem |
| collection | DOAJ |
| description | Background. Malaria is still a public health problem in Saudi Arabia specifically in the Jazan region. Plasmodium falciparum knob-associated histidine-rich proteins (PfKAHRPs) play an important role in cerebral malaria pathophysiology as well as pathogenesis of P. falciparum infections. The repeat region of PfKAHRP C-terminal interaction domain has been found to bind to the infected red blood cells and the vascular endothelium. Thus, this study aimed to assess the allelic variations, genetic diversity, and natural selection acting at the C-terminal PfKAHRP between parasite isolates from Saudi Arabia. Materials and Methods. The PfKHARP C-terminal interaction domain was successfully PCR-amplified and sequence data from 441 clinical isolates from Saudi Arabia were obtained. The DnaSP v5.10 software was used to determine the genetic diversity, polymorphism, haplotype, and natural selection. Haplotype network analysis was constructed by using the median-joining method in the NETWORK version 5.0.0.1 software. Results. Alignment and analysis of 441 C-terminal PfKAHRP-deduced amino acid sequences identified 5 genotypes (I–V) based on the decapeptide repeat arrangements (TKEASTSKEA, TKEASTSKGA, TKEASTTEGA, and TKEASTSKRA). Among the repeat types, Type I (49.43%, 218/441) was the most abundant in Saudi Arabia, followed by Type II (48.29%, 213/441). Overall, the nucleotide diversity in the PfKHARP C-terminal region was found to be low in Saudi Arabia (π = 0.00142); however, natural selection tests indicated positive selection (dN-dS = 1.64, P<0.05) which was due to the variations within the repeat motifs. Genealogical relationship haplotype network of PfKAHRP from 4 different countries (i.e., Saudi Arabia, Iran, Burundi, and India) revealed 1 major shared haplotype cluster (H_1) with samples representative from all 4 countries (Saudi Arabia; n = 441, Burundi; n = 4, Iran; n = 13, and India; n = 1). Conclusion. Since this is the first study to report on genetic diversity of C-terminal PfKAHRP interaction domain and the repeat motifs from clinical samples in Saudi Arabia, it will contribute towards the rational design of antiadhesion drug therapies for P. falciparum malaria. |
| format | Article |
| id | doaj-art-bee5886616134f5683141022d959dd15 |
| institution | Kabale University |
| issn | 1687-9694 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
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| series | Journal of Tropical Medicine |
| spelling | doaj-art-bee5886616134f5683141022d959dd152025-02-03T05:58:56ZengWileyJournal of Tropical Medicine1687-96942022-01-01202210.1155/2022/3740889Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi ArabiaSaad M. Bin Dajem0Md Atique Ahmed1Marie Fe F Bohol2Syeda Wasfeea Wazid3Mohammed I. Shafeai4Fuad H. Rudiny5Ali M. Motaen6Kareem Morsy7Hani Alothaid8Ahmed A. Al-Qahtani9Department of BiologyICMR-Regional Medical Research CenterDepartment of Infection and ImmunityArogyo Society of Health, Welfare and Support (ASHWAS)Sabya General HospitalSabya General HospitalSabya General HospitalDepartment of BiologyDepartment of Basic SciencesDepartment of Infection and ImmunityBackground. Malaria is still a public health problem in Saudi Arabia specifically in the Jazan region. Plasmodium falciparum knob-associated histidine-rich proteins (PfKAHRPs) play an important role in cerebral malaria pathophysiology as well as pathogenesis of P. falciparum infections. The repeat region of PfKAHRP C-terminal interaction domain has been found to bind to the infected red blood cells and the vascular endothelium. Thus, this study aimed to assess the allelic variations, genetic diversity, and natural selection acting at the C-terminal PfKAHRP between parasite isolates from Saudi Arabia. Materials and Methods. The PfKHARP C-terminal interaction domain was successfully PCR-amplified and sequence data from 441 clinical isolates from Saudi Arabia were obtained. The DnaSP v5.10 software was used to determine the genetic diversity, polymorphism, haplotype, and natural selection. Haplotype network analysis was constructed by using the median-joining method in the NETWORK version 5.0.0.1 software. Results. Alignment and analysis of 441 C-terminal PfKAHRP-deduced amino acid sequences identified 5 genotypes (I–V) based on the decapeptide repeat arrangements (TKEASTSKEA, TKEASTSKGA, TKEASTTEGA, and TKEASTSKRA). Among the repeat types, Type I (49.43%, 218/441) was the most abundant in Saudi Arabia, followed by Type II (48.29%, 213/441). Overall, the nucleotide diversity in the PfKHARP C-terminal region was found to be low in Saudi Arabia (π = 0.00142); however, natural selection tests indicated positive selection (dN-dS = 1.64, P<0.05) which was due to the variations within the repeat motifs. Genealogical relationship haplotype network of PfKAHRP from 4 different countries (i.e., Saudi Arabia, Iran, Burundi, and India) revealed 1 major shared haplotype cluster (H_1) with samples representative from all 4 countries (Saudi Arabia; n = 441, Burundi; n = 4, Iran; n = 13, and India; n = 1). Conclusion. Since this is the first study to report on genetic diversity of C-terminal PfKAHRP interaction domain and the repeat motifs from clinical samples in Saudi Arabia, it will contribute towards the rational design of antiadhesion drug therapies for P. falciparum malaria.http://dx.doi.org/10.1155/2022/3740889 |
| spellingShingle | Saad M. Bin Dajem Md Atique Ahmed Marie Fe F Bohol Syeda Wasfeea Wazid Mohammed I. Shafeai Fuad H. Rudiny Ali M. Motaen Kareem Morsy Hani Alothaid Ahmed A. Al-Qahtani Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia Journal of Tropical Medicine |
| title | Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia |
| title_full | Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia |
| title_fullStr | Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia |
| title_full_unstemmed | Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia |
| title_short | Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia |
| title_sort | genetic diversity repeat motifs and natural selection at the c terminal knob associated histidine rich protein kahrp of plasmodium falciparum clinical samples from saudi arabia |
| url | http://dx.doi.org/10.1155/2022/3740889 |
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