Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia

Yap, Nan Jiun; Goh, Xiang Ting; Koehler, Anson V.; William, Timothy; Yeo, Tsin Wen; Vythilingam, Indra; Gasser, Robin B.; Lim, Yvonne Ai Lian

doi:10.1016/j.meegid.2017.06.019

Cited by 16 publications

(30 citation statements)

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“…The 165 singleton variable sites were detected indicated that new and rare variant were present indicating population expansion however, Li and Fu’s D* and F* did not show significant negative values. Overall, the full-length gene showed significant negative selection (− 7.43, P < 0.000) and similar significant negative selection has been recently reported for invasion genes pknbpxa , pkmsp3 , and pkmsp1 [ 27 – 29 ]. The phylogenetic tree showed separation of the P. knowlesi MSP1P isolates from Malaysian Borneo into 2 clusters while the laboratory lines from Peninsular Malaysia formed a third cluster.…”

Section: Discussionsupporting

confidence: 81%

“…A recent study showed that polymorphisms within the merozoite invasion genes (normocyte binding protein xa and xb , nbpxa and nbpxb ) of P. knowlesi were linked to hyperparasitaemia and disease severity in human infections [ 26 ]. Potential vaccine candidates like Duffy binding protein (DBP), merozoite surface protein (MSP) 1 and 3, normocyte binding protein xa have recently been studied from P. knowlesi clinical isolates [ 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Genetic diversity and natural selection of Plasmodium knowlesi merozoite surface protein 1 paralog gene in Malaysia

Ahmed

Muh

Han

2018

Malar J

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BackgroundHuman infections due to the monkey malaria parasite Plasmodium knowlesi is on the rise in most Southeast Asian countries specifically Malaysia. The C-terminal 19 kDa domain of PvMSP1P is a potential vaccine candidate, however, no study has been conducted in the orthologous gene of P. knowlesi. This study investigates level of polymorphisms, haplotypes and natural selection of full-length pkmsp1p in clinical samples from Malaysia.MethodsA total of 36 full-length pkmsp1p sequences along with the reference H-strain and 40 C-terminal pkmsp1p sequences from clinical isolates of Malaysia were downloaded from published genomes. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 and MEGA 5.0 software. Genealogical relationships were determined using haplotype network tree in NETWORK software v5.0. Population genetic differentiation index (FST) and population structure of parasite was determined using Arlequin v3.5 and STRUCTURE v2.3.4 software.ResultsComparison of 36 full-length pkmsp1p sequences along with the H-strain identified 339 SNPs (175 non-synonymous and 164 synonymous substitutions). The nucleotide diversity across the full-length gene was low compared to its ortholog pvmsp1p. The nucleotide diversity was higher toward the N-terminal domains (pkmsp1p-83 and 30) compared to the C-terminal domains (pkmsp1p-38, 33 and 19). Phylogenetic analysis of full-length genes identified 2 distinct clusters of P. knowlesi from Malaysian Borneo. The 40 pkmsp1p-19 sequences showed low polymorphisms with 16 polymorphisms leading to 18 haplotypes. In total there were 10 synonymous and 6 non-synonymous substitutions and 12 cysteine residues were intact within the two EGF domains. Evidence of strong purifying selection was observed within the full-length sequences as well in all the domains. Shared haplotypes of 40 pkmsp1p-19 were identified within Malaysian Borneo haplotypes.ConclusionsThis study is the first to report on the genetic diversity and natural selection of pkmsp1p. A low level of genetic diversity and strong evidence of negative selection was detected and observed in all the domains of pkmsp1p of P. knowlesi indicating functional constrains. Shared haplotypes were identified within pkmsp1p-19 highlighting further evaluation using larger number of clinical samples from Malaysia.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2256-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Genetic diversity and natural selection of Plasmodium knowlesi merozoite surface protein 1 paralog gene in Malaysia

Ahmed

Muh

Han

2018

Malar J

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“…Hitherto, proteins of P. knowlesi involved in invasion of erythrocytes are generally under purifying (negative) selection ( Table 1 ), in most cases different from those of P. vivax and P. falciparum . 73 – 83 Negative selection may imply that the genes are under functional constrains. At the same time, the mutations are deleterious to the parasite and the P. knowlesi population is screening for best-adapted variants.…”

Section: Molecular Epidemiology and Diversitymentioning

confidence: 99%

<em>Plasmodium knowlesi</em> malaria: current research perspectives

Amir¹,

Cheong²,

Silva³

et al. 2018

IDR

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Originally known to cause simian malaria, Plasmodium knowlesi is now known as the fifth human malaria species. Since the publishing of a report that largely focused on human knowlesi cases in Sarawak in 2004, many more human cases have been reported in nearly all of the countries in Southeast Asia and in travelers returning from these countries. The zoonotic nature of this infection hinders malaria elimination efforts. In order to grasp the current perspective of knowlesi malaria, this literature review explores the different aspects of the disease including risk factors, diagnosis, treatment, and molecular and functional studies. Current studies do not provide sufficient data for an effective control program. Therefore, future direction for knowlesi research is highlighted here with a final aim of controlling, if not eliminating, the parasite.

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“…A recent P. knowlesi study showed association of polymorphisms within the merozoite invasion genes (normocyte binding protein xa and xb , nbpxa and nbpxb ) with high parasite counts and disease severity in human infections [ 17 ]. A number of blood stage antigens like Duffy binding protein (DBP), merozoite surface protein 1 (MSP-1), MSP-1 paralog, MSP-3 and nbpxa have very recently been studied from P. knowlesi clinical isolates but none has been shown to be under positive natural selection [ 18 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia

Ahmed

Lau

Quan

2018

Malar J

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BackgroundPlasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falciparum, however, no study has been done in the orthologous gene of P. knowlesi. This study investigates nucleotide diversity, haplotypes, natural selection and population differentiation of full-length pktrap genes in clinical samples from Malaysia.MethodsForty full-length pktrap sequences from clinical isolates of Malaysia along with the reference H-strain were downloaded from published databases. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. McDonald–Kreitman test was conducted using P. vivax and Plasmodium coatneyi as ortholog sequence in DnaSP 5.10 software. Population genetic differentiation index (FST) of parasite populations was determined using Arlequin v3.5. Phylogenetic relationships between trap ortholog genes were determined using MEGA 5.0 software.ResultsComparison of 40 full-length pktrap sequences along with the H-strain identified 74 SNPs (53 non-synonymous and 21 synonymous substitutions) resulting in 29 haplotypes. Analysis of the full-length gene showed that the nucleotide diversity was lower compared to its nearest ortholog pvtrap. Domain-wise analysis indicated that the proline/asparagine rich region had higher nucleotide diversity compared to the von Willebrand factor domain and the thrombospondin-type-1 domain. McDonald–Kreitman test identified that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. knowlesi was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. knowlesi and P. vivax. The von Willebrand factor domain also indicated balancing selection using MK test, however, it did not give significant results when tested with P. coatneyi as an outgroup. Phylogenetic analysis of full-length genes identified three distinct sub-clusters of P. knowlesi, one originating from Peninsular Malaysia and two originating from Malaysian Borneo. High population differentiation values was observed within samples from Peninsular Malaysia and Malaysian Borneo.ConclusionsThis study is the first to report on the genetic diversity and natural selection of full-length pktrap. Low level of genetic diversity was found across the full-length gene of pktrap. Balancing selection of the von Willebrand factor domain indicated that TRAP could be a target in inducing immune response against P. knowlesi infections. However, higher number of samples would be necessary to further confirm the findings.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2423-1) contains supplementary material, which is available to authorized users.

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Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia

Cited by 16 publications

References 48 publications

Genetic diversity and natural selection of Plasmodium knowlesi merozoite surface protein 1 paralog gene in Malaysia

Genetic diversity and natural selection of Plasmodium knowlesi merozoite surface protein 1 paralog gene in Malaysia

<em>Plasmodium knowlesi</em> malaria: current research perspectives

Diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia

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