Genetic diversity and natural selection analysis of VAR2CSA and vir genes: implication for vaccine development

TL;DR

This study analyzes genetic diversity in malaria-related genes to understand their evolution and inform vaccine development.

Contribution

The study reveals high genetic diversity and similar evolutionary patterns in VAR2CSA and vir genes across regions, important for vaccine design.

Findings

High genetic diversity observed in VAR2CSA and vir genes across Southeast Asia and sub-Saharan Africa.

Vir genes 12 and 21 show higher diversity compared to vir 4 and vir 27.

DBL3X fragment of VAR2CSA is the most diverse with high haplotype diversity.

Abstract

Variable surface antigens (VSAs) encoded by var and vir genes in Plasmodium falciparum and Plasmodium vivax, respectively, are known to be involved in malaria pathogenesis and host immune escape through antigenic variations. Knowledge of the genetic diversity of these antigens is essential for malaria control and effective vaccine development. In this study, we analysed the genetic diversity and evolutionary patterns of two fragments (DBL2X and DBL3X) of VAR2CSA gene and four vir genes (vir 4, vir 12, vir 21 and vir 27) from different endemic regions, including Southeast Asia and sub-Saharan Africa. High levels of segregating sites (S) and haplotype diversity (Hd) were observed in both var and vir genes. Among vir genes, vir 12 (S = 131, Hd = 0.996) and vir 21 (S = 171, Hd = 892) were found to be more diverse as compared to vir 4 (S = 11, Hd = 0.748) and vir 27 (S = 23, Hd = 0.814). DBL2X (S = 99, Hd = 0.996) and DBL3X (S = 307, Hd = 0.999) fragments showed higher genetic diversity. Our analysis indicates that var and vir genes are highly diverse and follow the similar evolutionary pattern globally. Some codons showed signatures of positive or negative selection pressure, but vir and var genes are likely to be under balancing selection. This study highlights the high variability of var and vir genes and underlines the need of functional experimental studies to determine the most relevant allelic forms for effective progress towards vaccine formulation and testing.

The online version contains supplementary material available at 10.1186/s44342-024-00009-0.

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