Highly conserved Plasmodium vivax genomes in Duffy-negative individuals from Sudan

Abstract

Abstract Duffy-negatives were previously thought to be immune to Plasmodium vivax infections due to Duffy binding protein’s (PvDBP1) inability to invade erythrocytes lacking Duffy antigen receptor for chemokines (DARC) expression. Nevertheless, reports of P. vivax cases are growing throughout Africa and among Duffy-negative people. Although there are alternative invasion mechanisms by P. vivax , the exact mechanisms in Duffy-negative individuals are unclear. Sudan, with a mixed Duffy-negative and Duffy-positive population, is ideal to study differences between these infections on epidemiological and genetic scales. The goal of this study was to compare Duffy-positive and Duffy-negative infections in Sudanese individuals on epidemiological and genomic scales. We collected epidemiological data and sequenced parasite genomes and found that Duffy-positive individuals had significantly higher parasitemia than Duffy-negatives. Furthermore, Duffy-positive infected P. vivax genomes were much more diverse than Duffy-negatives, across all 14 chromosomes and 44 specific erythrocyte binding gene candidates. Genes of the merozoite surface protein family account for much of the genetic diversity found. Many erythrocyte binding gene candidates are under selection pressure, both positive and negative. Finally, in DBP and RBP genes, as well as TRAg 38, changes in amino acids in the binding regions to a structurally different residue could affect erythrocyte binding affinity and antigenic conformation.