Few Plasmodium falciparum merozoite ligand and erythrocyte receptor pairs show evidence of balancing selection

Abstract

Erythrocyte surface proteins have been identified as receptors of Plasmodium falciparum merozoite proteins. The ligand-receptor interactions enable the parasite to invade human erythrocytes, initiating the clinical symptoms of malaria. These interactions are likely to have had an evolutionary impact on the genes that encode the ligand and receptor proteins. We used sequence data from Kilifi, Kenya to detect departures from neutrality in a paired analysis of P. falciparum merozoite ligands and their erythrocyte receptor genes from the same population. We genotyped parasite and human DNA obtained from 93 individuals with severe malaria. We examined six merozoite ligands EBA175, EBL1, EBA140, MSP1, Rh4 and Rh5, and their corresponding erythrocyte receptors, glycophorin (Gyp) A, GypB, GypC, band 3, complement receptor (CR) 1 and basigin, focusing on the regions involved in the ligand-receptor interactions. Positive Tajima's D values (>1) were observed only in the MSP1 C-terminal region and EBA175 region II, while negative values (<−1) were observed in EBL-1 region II, Rh4, basigin exons 3 and 5, CR1 exon 5, Gyp B exons 2, 3 and 4 and Gyp C exon 2. Additionally, ebl-1 region II and basigin exon 3 showed extreme negative values in all three tests, Tajima's D, Fu & Li D* and F*, ≤ − 2. A large majority of the erythrocyte receptor and merozoite genes have a negative Tajima's D even when compared with previously published whole genome data. Thus, highlighting EBA175 region II and MSP1–33, as outlier genes with a positive Tajima's D (>1). Both these genes contain multiple polymorphisms, which in the case of EBA175 may counteract receptor polymorphisms and/or evade host immune responses and in MSP1 the polymorphisms may primarily evade host immune responses.

Population genetic and biophysical evidences reveal that purifying selection shapes the genetic landscape of Plasmodium falciparum RH ligands in Chhattisgarh and West Bengal, India

“…Despite an overall abundance of low frequency polymorphisms, the structures of the parasite population from different geographical regions showed remarkable genetic differentiation possibly due to factors such as local adaptation and/or random genetic drift. Nevertheless, frequency of C203Y was found to be high in Kenya and Mali, as well [43,44].…”

Plasmodium falciparum Malaria Parasites in Ghana Show Signatures of Balancing Selection at Artemisinin Resistance Predisposing Background Genes

“…We found 579 P. falciparum genes with Tajima’s D greater than 1 ( Figure 5 , Supplemental Table S1 ). 26 - 28 Of these, genomic positions above the 90th percentile of the Tajima’s D distribution showed gene ontology biochemical processes spanning multiple pathways ( Supplemental Table S2 ). There were no SNPs in the pfk13 gene and none of the reported SNPs that form the background genome for ARTr to emerge were identified in this analysis ( Supplemental Table S3 ).…”

Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

“…Balancing selection (BS) has been studied in Plasmodium parasites extensively. In this genus, proteins that interact directly with host cells maintain high genetic diversity ( Mobegi et al 2014 ; Ochola-Oyier et al 2019 ; Hocking et al 2020 ), as do proteins that are exported to the surface of erythrocytes ( Jeffares et al 2007 ). BS signals are also enriched in solvent-exposed regions of proteins consistent with selection for increased diversity via a rare allele advantage ( Guy et al 2018 ).…”