Abstract
BackgroundThe 175-kDa erythrocyte binding antigen (EBA-175) of Plasmodium falciparum plays a crucial role in merozoite invasion into human erythrocytes. EBA-175 is believed to have been under diversifying selection; however, there have been no studies investigating the effect of dispersal of humans out of Africa on the genetic variation of EBA-175 in P. falciparum.MethodsThe PCR-direct sequencing was performed for a part of the eba-175 gene (regions II and III) using DNA samples obtained from Thai patients infected with P. falciparum. The divergence times for the P. falciparum eba-175 alleles were estimated assuming that P. falciparum/Plasmodium reichenowi divergence occurred 6 million years ago (MYA). To examine the possibility of diversifying selection, nonsynonymous and synonymous substitution rates for Plasmodium species were also estimated.ResultsA total of 32 eba-175 alleles were identified from 131 Thai P. falciparum isolates. Their estimated divergence time was 0.13–0.14 MYA, before the exodus of humans from Africa. A phylogenetic tree for a large sequence dataset of P. falciparumeba-175 alleles from across the world showed the presence of a basal Asian-specific cluster for all P. falciparum sequences. A markedly more nonsynonymous substitutions than synonymous substitutions in region II in P. falciparum was also detected, but not within Plasmodium species parasitizing African apes, suggesting that diversifying selection has acted specifically on P. falciparumeba-175.ConclusionsPlasmodium falciparumeba-175 genetic diversity appeared to increase following the exodus of Asian ancestors from Africa. Diversifying selection may have played an important role in the diversification of eba-175 allelic lineages. The present results suggest that the dispersals of humans out of Africa influenced significantly the molecular evolution of P. falciparum EBA-175.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0820-2) contains supplementary material, which is available to authorized users.
Highlights
The 175-kDa erythrocyte binding antigen (EBA-175) of Plasmodium falciparum plays a crucial role in merozoite invasion into human erythrocytes
The 175-kDa erythrocyte binding antigen (EBA-175) of P. falciparum binds with a sialic acid on human glycophorin A (GYPA); the interaction of these molecules is the part of a major pathway for malaria parasite invasion into erythrocytes
Detection of eba‐175 alleles The nucleotide sequences of regions II and III of P. falciparum eba-175 were obtained by PCR-direct sequencing
Summary
The 175-kDa erythrocyte binding antigen (EBA-175) of Plasmodium falciparum plays a crucial role in merozoite invasion into human erythrocytes. The 175-kDa erythrocyte binding antigen (EBA-175) of P. falciparum binds with a sialic acid on human glycophorin A (GYPA); the interaction of these molecules is the part of a major pathway for malaria parasite invasion into erythrocytes. Previous studies have shown a significant excess of nonsynonymous substitutions over synonymous substitutions in this region in P. falciparum [8,9,10,11]; no studies have assessed to date the ratio of nonsynonymous to synonymous substitutions in other closely related Plasmodium species. When human and macaque genomes were compared, the gypa gene shows the highest number of nonsynonymous substitutions per nonsynonymous sites among 280 genes [10]. The high level of genetic polymorphisms shown by eba-175 and gypa is likely to result from host–pathogen coevolution
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