Geographical and temporal dynamics of genetic diversity of Plasmodium falciparum merozoite surface proteins 1/2 in India

The high genetic diversity of Plasmodium falciparum (Pf) is a big obstacle to successful vaccine development programs. Here, the geographical and temporal dynamics of the genetic diversity of Indian Pf isolates from patients living in Ranchi, Raipur, Mewat, and Rourkela were analyzed. Typing and frequency of merozoite surface protein 1 and 2 genes (pfmsp1/2), their genotypes, clonality, heterozygosity, multiplicity of infection, and neutral evolution metrics were computed. A phylogenetic analysis was also performed for these two genes. The dominant allelic types were K1 (55%) and MAD20 (55%) for msp1, and FC27 (64.7%) for msp2. Infections were mainly monoclonal in Ranchi and Mewat while polyclonal in Raipur and Rourkela. Polyclonal infections dropped from 57.1 to 71.3% in 2013 to 33.3–33.4% in 2016 in Raipur. K1 and MAD20 sequences were highly diverse due to the organization of the amino acid units SGG, SVA, SVT, and SGN. The IC/3D7-related G,S,A-rich region showed a large variation of four to eight amino acid repeats, including mostly GAVASA (81.8%), GSGA (54.5%), and GASGSA (45.5%). The 32-amino acid sequence of the FC27 type was present in all isolates with several mutations. The msp1/2 sequences were not under neutral evolution, except the K1 family, which is under balancing selection. The msp1/2 sequences are phylogenetically closer to previous Indian sequences than those from Africa, Asia, the Americas, and Oceania. This study outlines a high genetic diversity of Pf infections with complex structure, and evolutionary signature changed with time.