Plasmodium falciparum Malaria Parasites in Ghana Show Signatures of Balancing Selection at Artemisinin Resistance Predisposing Background Genes

Abstract

Sub-Saharan Africa is courting the risk of artemisinin resistance (ARTr) emerging in Plasmodium falciparum malaria parasites. Current molecular surveillance efforts for ARTr have been built on the utility of P. falciparum kelch13 ( pfk13) validated molecular markers. However, whether these molecular markers will serve the purpose of early detection of artemisinin-resistant parasites in Ghana is hinged on a pfk13 dependent evolution. Here, we tested the hypothesis that the background pfk13 genome may be present before the pfk13 ARTr-conferring variant(s) is selected and that signatures of balancing selection on these genomic loci may serve as an early warning signal of ARTr. We analyzed 12 198 single nucleotide polymorphisms (SNPs) in Ghanaian clinical isolates in the Pf3K MalariaGEN dataset that passed a stringent filtering regimen. We identified signatures of balancing selection in 2 genes (phosphatidylinositol 4-kinase and chloroquine resistance transporter) previously reported as background loci for ARTr. These genes showed statistically significant and high positive values for Tajima’s D, Fu and Li’s F, and Fu and Li’s D. This indicates that the biodiversity required to establish a pfk13 background genome may have been primed in clinical isolates of P. falciparum from Ghana as of 2010. Despite the absence of ARTr in Ghana to date, our finding supports the current use of pfk13 for molecular surveillance of ARTr in Ghana and highlights the potential utility of monitoring malaria parasite populations for balancing selection in ARTr precursor background genes as early warning molecular signatures for the emergence of ARTr.

Molecular speciation of Plasmodium and multiplicity of P. falciparum infection in the Central region of Ghana

“…The current study demonstrated that there is clonal expansion of P . falciparum infections in the Central region with 55.5% of the study participants having between 2–6, similar to the 56% prevalence reported by Tandoh et al [ 44 ]. Furthermore, the prevalence of polyclonal infection also corroborates with findings on parasite diversity in other parts of Ghana, which concluded that P .…”

Population structure analysis to explore genetic diversity and geographical distribution characteristics of cultivated-type tea plant in Guizhou Plateau

“…Previous studies showed population bottlenecks and/or balancing selection when positive Tajima’s D values were determined for a population [ 39 , 40 ]. The positive Tajima’s D values of all tea populations here suggest that they all underwent population bottlenecks and/or balancing selection (Table 2 ).…”

“…Previous studies demonstrated that positive Tajima’s D values indicated population bottlenecks and/or balancing selection [ 39 , 40 ]. Positive Tajima’s D values were observed in all populations in the present study.…”

Population Structure Analysis Revealed Water or Ancient Hub-induced Genetic Diversity of Cultivated-type Tea Plants in Guizhou Plateau

“…Previous studies showed that there exist population bottlenecks and/or balancing selection when the positive Tajima's D values was detected in a population [43,44]. The positive Tajima's D values were observed in all these populations, suggesting that these populations existed population bottlenecks, and/or balancing selection (Table 2).…”