Plasmodium vivax synonymous substitution frequencies, evolution and population structure deduced from diversity in AMA 1 and MSP 1 genes

Polymorphic regions of the genes encoding Plasmodium vivax apical membrane antigen 1 (PvAMA1) and P. vivax merozoite surface protein 1 (PvMSP1) were s equenced to examine population diversity both within and between geographic al areas. Sequences were obtained for 219 isolates for PvAMA1 and for 175 i solates for PvMSP1 from Africa, China, India, Indonesia, Philippines, Papua New Guinea, Solomon Islands and Thailand. Over half of the isolates were o btained from different regions within the Philippines, and this was used to look at the diversity within a country. Sixty nine haplotypes and 22 polym orphic sites in a 414-bp region of PvAMA1 and 41 haplotypes and 34 polymorp hic sites in a 249-bp fragment of PvMSP1 were detected. For both PvAMA1 and PvMSP1, four previously unreported polymorphic nucleotide positions were i dentified. Population analysis indicated that there were significant differ ences in allele frequencies between different regions but these differences were small compared to the diversity within populations (Fixation index, F -ST, of 0.126 and 0.078 for PvAMA1 and PvMSP1, respectively). PvAMA1 and Pv MSP1 had similar nonsynonymous substitution frequencies but surprisingly, t he synonymous substitution fre-quency for PvMSP1 was eight times the freque ncy for PvAMA1 suggesting that synonymous substitutions in at least PvAMA1 are not neutral. (C) 2000 Elsevier Science B.V. All rights reserved.