Genetic polymorphism of Duffy binding protein in Pakistan Plasmodium vivax isolates

Abstract

Plasmodium vivax Duffy binding protein (PvDBP) is crucial for erythrocyte invasion, interacting with the Duffy Antigen Receptor for Chemokines (DARC) on the erythrocyte surface. The amino-terminal cysteine-rich region II of PvDBP (PvDBPII) is a promising blood stage vaccine candidate, yet the genetic polymorphisms of this protein in global P. vivax isolates complicate the design of effective vaccines against vivax malaria. This study analyzed the genetic polymorphism of PvDBPII in Pakistan P. vivax isolates. A total of 29 single nucleotide polymorphisms (SNPs), including 22 nonsynonymous SNPs, were identified in 118 Pakistan PvDBPII. Most amino acid substitutions occurred in subdomains II and III, with six commonly observed in the global PvDBPII population. The amino acid change patterns in Pakistan PvDBPII generally mirrored those in global PvDBPII, although the frequencies of amino acid changes varied by country. Nucleotide diversity in Pakistan PvDBPII was comparable to that found in global PvDBPII. Evidence of natural selection and recombination in Pakistan PvDBPII aligned with observations in global PvDBPII. Analysis of the haplotype network of global PvDBPII revealed a complexed network of 167 haplotypes, but no geographical clustering was observed. The findings are crucial for understanding the genetic characteristics of Pakistan PvDBPII. A comprehensive analysis of nucleotide diversity and evolutionary trends in the global PvDBPII population offers valuable insights for the development of vivax malaria vaccines based on this antigen.