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- Title
Whole Genome Sequencing of Field Isolates Reveals a Common Duplication of the Duffy Binding Protein Gene in Malagasy Plasmodium vivax Strains.
- Authors
Menard, Didier; Chan, Ernest R.; Benedet, Christophe; Ratsimbasoa, Arsène; Kim, Saorin; Chim, Pheaktra; Do, Catherine; Witkowski, Benoit; Durand, Remy; Thellier, Marc; Severini, Carlo; Legrand, Eric; Musset, Lise; Nour, Bakri Y. M.; Mercereau-Puijalon, Odile; Serre, David; Zimmerman, Peter A.
- Abstract
Background: Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes. Methods/Principal Findings: Through recent whole genome sequencing we obtained ≥70× coverage of the P. vivax genome from five field-isolates, resulting in ≥93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported. Conclusions/Significance: The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations. Author Summary: Malaria results from infection of human red blood cells (RBC) by Plasmodium parasite's merozoite. For Plasmodium vivax the process of RBC invasion has been hypothesized to depend on interactions between the parasite's Duffy binding protein (PvDBP) and human Duffy blood group antigen because Duffy-negative people (most often people of African descent) were shown to be highly resistant to RBC infection and disease. Over the past five years, researchers are reporting with increasing frequency that Duffy-negative individuals are infected with P. vivax. This raises new questions as to how P. vivax infects the RBC when the Duffy blood group antigen is not available. Here we show that the parasite's Duffy binding protein gene has been duplicated in multiple P. vivax strains, especially at high prevalence in Madagascar. The specificity and prevalence of this polymorphism suggest that the parasite genome has responded to the barrier of Duffy negativity through the duplication of the PvDBP gene. Our results indicate that the PvDBP duplication is a recent event and provide novel research avenues to understand alternative pathways for P. vivax RBC invasion.
- Subjects
MADAGASCAR; EAST Africa; WHOLE genome sequencing; CARRIER proteins; PLASMODIUM vivax; BLOOD group antigens; GENE rearrangement; BABESIA
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 11, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002489