Hawadak Joseph, Arya Aditi, Chaudhry Shewta, Singh Vineeta
ICMR-National Institute of Malaria Research (NIMR), Delhi, 110077, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Genomics Inform. 2024 Jul 15;22(1):11. doi: 10.1186/s44342-024-00009-0.
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.
恶性疟原虫和间日疟原虫中分别由var和vir基因编码的可变表面抗原（VSA），已知通过抗原变异参与疟疾发病机制和宿主免疫逃逸。了解这些抗原的遗传多样性对于疟疾控制和有效的疫苗开发至关重要。在本研究中，我们分析了来自不同流行地区（包括东南亚和撒哈拉以南非洲）的VAR2CSA基因的两个片段（DBL2X和DBL3X）以及四个vir基因（vir 4、vir 12、vir 21和vir 27）的遗传多样性和进化模式。在var和vir基因中均观察到高水平的分离位点（S）和单倍型多样性（Hd）。在vir基因中，与vir 4（S = 11，Hd = 0.748）和vir 27（S = 23，Hd = 0.814）相比，发现vir 12（S = 131，Hd = 0.996）和vir 21（S = 171，Hd = 0.892）具有更高的多样性。DBL2X（S = 99，Hd = 0.996）和DBL3X（S = 307，Hd = 0.999）片段显示出更高的遗传多样性。我们的分析表明，var和vir基因高度多样，并且在全球范围内遵循相似的进化模式。一些密码子显示出正选择或负选择压力的特征，但vir和var基因可能处于平衡选择之下。本研究突出了var和vir基因的高变异性，并强调需要进行功能实验研究以确定对疫苗配方和测试的有效进展最相关的等位基因形式。
