Genetic diversity and natural selection of three blood-stage 6-Cys proteins in Plasmodium vivax populations from the China-Myanmar endemic border

Pv12, Pv38 and Pv41, the three 6-Cys family proteins which are expressed in the blood-stage of vivax malaria, might be involved in merozoite invasion activity and thus be potential vaccine candidate antigens of Plasmodium vivax. However, little information is available concerning the genetic diversity and natural selection of these three proteins. In the present study, we analyzed the amino acid sequences of P. vivax blood-stage 6-Cys family proteins in comparison with the homologue proteins of Plasmodium cynomolgi strain B using bioinformatic methods. We also investigated genetic polymorphisms and natural selection of these three genes in P. vivax populations from the China-Myanmar endemic border. The three P. vivax blood-stage 6-Cys proteins were shown to possess a signal peptide at the N-terminus, containing two s48/45 domains, and Pv12 and Pv38 have a GPI-anchor motif at the C-terminus. Then, 22, 21 and 29 haplotypes of pv12, pv38 and pv41 were identified out of 45, 38 and 40 isolates, respectively. The dN/dS values for Domain II of pv38 and pv41 were 3.33880 and 5.99829, respectively, suggesting positive balancing selection for these regions. Meanwhile, the C-terminus of pv41 showed high nucleotide diversity, and Tajima's D test suggested that this fragment could be under positive balancing selection. Overall, our results have significant implications, providing a genetic basis for blood-stage malaria vaccine development based on these three 6-Cys proteins.