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

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

Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a mole...

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Main Authors:	Yap, N.J., Goh, X.T., Koehler, A.V., William, T., Yeo, T.W., Vythilingam, I., Gasser, R.B., Lim, Y.A.L.
Format:	Article
Published:	Elsevier 2017
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/17587/ http://dx.doi.org/10.1016/j.meegid.2017.06.019
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spelling	my.um.eprints.175872017-08-03T06:19:43Z http://eprints.um.edu.my/17587/ Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia Yap, N.J. Goh, X.T. Koehler, A.V. William, T. Yeo, T.W. Vythilingam, I. Gasser, R.B. Lim, Y.A.L. R Medicine Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42 kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42 kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine. However, to date, no study has yet investigated the sequence diversity of the gene encoding P. knowlesi MSP-142 (comprising Pk-msp-119 and Pk-msp-133) among isolates in Malaysia. The present study explored this aspect. Twelve P. knowlesi isolates were collected from patients from hospitals in Selangor and Sabah Borneo, Malaysia, between 2012 and 2014. The Pk-msp-142 gene was amplified by PCR and directly sequenced. Haplotype diversity (Hd) and nucleotide diversity (л) were studied among the isolates. There was relatively high genetic variation among P. knowlesi isolates; overall Hd and л were 1 ± 0.034 and 0.01132 ± 0.00124, respectively. A total of nine different haplotypes related to amino acid alterations at 13 positions, and the Pk-MSP-119 sequence was found to be more conserved than Pk-msp-133. We have found evidence for negative selection in Pk-msp-42 as well as the 33 kDa and 19 kDa fragments by comparing the rate of non-synonymous versus synonymous substitutions. Future investigations should study large numbers of samples from disparate geographical locations to critically assess whether this molecule might be a potential vaccine target for P. knowlesi. Elsevier 2017 Article PeerReviewed Yap, N.J. and Goh, X.T. and Koehler, A.V. and William, T. and Yeo, T.W. and Vythilingam, I. and Gasser, R.B. and Lim, Y.A.L. (2017) Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia. Infection, Genetics and Evolution, 54. pp. 39-46. ISSN 1567-1348 http://dx.doi.org/10.1016/j.meegid.2017.06.019 doi:10.1016/j.meegid.2017.06.019
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Yap, N.J. Goh, X.T. Koehler, A.V. William, T. Yeo, T.W. Vythilingam, I. Gasser, R.B. Lim, Y.A.L. Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
description	Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42 kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42 kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine. However, to date, no study has yet investigated the sequence diversity of the gene encoding P. knowlesi MSP-142 (comprising Pk-msp-119 and Pk-msp-133) among isolates in Malaysia. The present study explored this aspect. Twelve P. knowlesi isolates were collected from patients from hospitals in Selangor and Sabah Borneo, Malaysia, between 2012 and 2014. The Pk-msp-142 gene was amplified by PCR and directly sequenced. Haplotype diversity (Hd) and nucleotide diversity (л) were studied among the isolates. There was relatively high genetic variation among P. knowlesi isolates; overall Hd and л were 1 ± 0.034 and 0.01132 ± 0.00124, respectively. A total of nine different haplotypes related to amino acid alterations at 13 positions, and the Pk-MSP-119 sequence was found to be more conserved than Pk-msp-133. We have found evidence for negative selection in Pk-msp-42 as well as the 33 kDa and 19 kDa fragments by comparing the rate of non-synonymous versus synonymous substitutions. Future investigations should study large numbers of samples from disparate geographical locations to critically assess whether this molecule might be a potential vaccine target for P. knowlesi.
format	Article
author	Yap, N.J. Goh, X.T. Koehler, A.V. William, T. Yeo, T.W. Vythilingam, I. Gasser, R.B. Lim, Y.A.L.
author_facet	Yap, N.J. Goh, X.T. Koehler, A.V. William, T. Yeo, T.W. Vythilingam, I. Gasser, R.B. Lim, Y.A.L.
author_sort	Yap, N.J.
title	Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
title_short	Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
title_full	Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
title_fullStr	Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
title_full_unstemmed	Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia
title_sort	genetic diversity in the c-terminus of merozoite surface protein 1 among plasmodium knowlesi isolates from selangor and sabah borneo, malaysia
publisher	Elsevier
publishDate	2017
url	http://eprints.um.edu.my/17587/ http://dx.doi.org/10.1016/j.meegid.2017.06.019
_version_	1643690459881537536
score	13.211869

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

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