Genetic diversity of the Plasmodium vivax phosphatidylinositol 3-kinase gene in two regions of the China-Myanmar border

Abstract

Artemisinin resistance in Plasmodium falciparum was associated with mutations in the propeller domain of the PfK13 gene and increased phosphatidylinositol-3′-kinase (PfPI3K) activity. Assessment of the genetic diversity of the PfK13 ortholog PvK12 in Plasmodium vivax field samples from the same hotspots of P. falciparum artemisinin resistance revealed a limited genetic diversity of PvK12. Following the same logic, we analyzed genetic variations of the PvPI3K gene in 188 P. vivax field isolates from two geographic locations along the China-Myanmar border. Overall, high genetic diversity of PvPI3K was observed; parasites from Yunnan's Tengchong County had higher genetic diversity than those from Laiza Township, Kachin State, Myanmar. Almost all the neutrality tests applied detected statistically significant deviation from zero. The negative Tajima's D values in both populations implicated that PvPI3K gene might have experienced either a directional selection or an expansion in population size. There was low linkage disequilibrium between the PvPI3K mutations in both populations, suggesting the existence of large, almost panmictic, parasite populations that enabled effective recombination. This later result was confirmed by the detection of a minimum of five recombination events in each population with two major breakpoints. Multiple tests for selection confirmed a signature of purifying selection on PvPI3K. All the amino acid mutations were predicted to be neutral for the PI3K protein's function. These findings provide insights on the genetic diversity of P. vivax populations along the China-Myanmar border.