Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the re...

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Autores principales:	Anthony Ford, Daniel Kepple, Beka Raya Abagero, Jordan Connors, Richard Pearson, Sarah Auburn, Sisay Getachew, Colby Ford, Karthigayan Gunalan, Louis H Miller, Daniel A Janies, Julian C Rayner, Guiyun Yan, Delenasaw Yewhalaw, Eugenia Lo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/30965ea5d37241d5bc75ea82bf8f930b
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spelling	oai:doaj.org-article:30965ea5d37241d5bc75ea82bf8f930b2021-12-02T20:23:25ZWhole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.1935-27271935-273510.1371/journal.pntd.0008234https://doaj.org/article/30965ea5d37241d5bc75ea82bf8f930b2020-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0008234https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale.Anthony FordDaniel KeppleBeka Raya AbageroJordan ConnorsRichard PearsonSarah AuburnSisay GetachewColby FordKarthigayan GunalanLouis H MillerDaniel A JaniesJulian C RaynerGuiyun YanDelenasaw YewhalawEugenia LoPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 14, Iss 10, p e0008234 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Anthony Ford Daniel Kepple Beka Raya Abagero Jordan Connors Richard Pearson Sarah Auburn Sisay Getachew Colby Ford Karthigayan Gunalan Louis H Miller Daniel A Janies Julian C Rayner Guiyun Yan Delenasaw Yewhalaw Eugenia Lo Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
description	Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale.
format	article
author	Anthony Ford Daniel Kepple Beka Raya Abagero Jordan Connors Richard Pearson Sarah Auburn Sisay Getachew Colby Ford Karthigayan Gunalan Louis H Miller Daniel A Janies Julian C Rayner Guiyun Yan Delenasaw Yewhalaw Eugenia Lo
author_facet	Anthony Ford Daniel Kepple Beka Raya Abagero Jordan Connors Richard Pearson Sarah Auburn Sisay Getachew Colby Ford Karthigayan Gunalan Louis H Miller Daniel A Janies Julian C Rayner Guiyun Yan Delenasaw Yewhalaw Eugenia Lo
author_sort	Anthony Ford
title	Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
title_short	Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
title_full	Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
title_fullStr	Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
title_full_unstemmed	Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
title_sort	whole genome sequencing of plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/30965ea5d37241d5bc75ea82bf8f930b
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Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

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