Abstract
Merozoite surface protein 7 (MSP-7) is a multigene family expressed during malaria blood-stage infection. MSP-7 forms complex with MSP-1 prior to merozoite egress from erythrocytes, and could affect merozoite invasion of erythrocytes. To characterize sequence variation in the orthologue in P. vivax (PvMSP-7), a gene member encoding PvMSP-7E was analyzed among 92 Thai isolates collected from 3 major endemic areas of Thailand (Northwest: Tak, Northeast: Ubon Ratchathani, and South: Yala and Narathiwat provinces). In total, 52 distinct haplotypes were found to circulate in these areas. Although population structure based on this locus was observed between each endemic area, no genetic differentiation occurred between populations collected from different periods in the same endemic area, suggesting spatial but not temporal genetic variation. Sequence microheterogeneity in both N- and C- terminal regions was predicted to display 4 and 6 α-helical domains, respectively. Signals of purifying selection were observed in α-helices II-X, suggesting structural or functional constraint in these domains. By contrast, α-helix-I spanning the putative signal peptide was under positive selection, in which amino acid substitutions could alter predicted CD4+ T helper cell epitopes. The central region of PvMSP-7E comprised the 5'-trimorphic and the 3'-dimorphic subregions. Positive selection was identified in the 3' dimorphic subregion of the central domain. A consensus of intrinsically unstructured or disordered protein was predicted to encompass the entire central domain that contained a number of putative B cell epitopes and putative protein binding regions. Evidences of intragenic recombination were more common in the central region than the remainders of the gene. These results suggest that the extent of sequence variation, recombination events and selective pressures in the PvMSP-7E locus seem to be differentially affected by protein secondary structure.