Reticulocyte Binding Protein Homologue 5 is a target of balancing selection in the Plasmodium falciparum population of Papua New Guinea

• DOI: 10.3389/fpara.2023.1288867
• Publication Date: 2023-12-22T04:38:06Z
• Authors: Myo T. Naung; Elijah Martin; Wilson Wong; Zahra Razook; Digjaya Utama; Andrew J. Guy; Shannon Takala Ha...; Alan F. Cowman; Enmoore Lin; Benson Kiniboro; Moses Laman; Ivo Mueller; Alyssa E. Barry
• Keywords: Basigin; Balancing selection; Nucleotide diversity

Plasmodium falciparum Reticulocyte Binding Protein Homologue (RH5), a leading malaria vaccine candidate, is essential for erythrocyte invasion by the parasite, interacting with human host receptor, basigin. RH5 has small number of polymorphisms relative to other blood-stage antigens, and in vitro studies have shown that vaccine-induced antibodies raised against are strain-transcending, however most investigating diversity been done Africa. Understanding genetic evolution antigens regions important their validation as candidates. In this study rh5 gene was sequenced 677 samples from longitudinal cohort Papua New Guinean (PNG) children aged 1-3 years. Of successfully sequenced, 566 were identified independent infections (i.e. one each pair identical sequences within hosts removed). A total 14 non-synonymous identified, eight ‘common’ population (minor allele frequency > 1%), 44 haplotypes ranging 1% 21%. Modeling common SNPs cryo-EM structure RH5/CyRPA/RIPR complex mapped them Basigin binding site near contact point CyRPA. Tajima’s D analyses corresponding nucleotide produced positive values indicating potential hotspots balancing selection. We attempted confirm whether these signals due immune selection measuring rate polymorphism between same host, association clinical symptoms, however, no such associations identified. Together results suggest while there evidence driving PNG P. population, escape not observed young children. Limited immunity therefore low selective pressure may explain result, alternatively evolutionary forces contribute at RH5-BSG interface PNG.