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Understanding the population genetics of genes which shape resistance to antimalarial drugs can help in devising novel control strategies. The high spread of the resistant strains of the malaria parasite Plasmodium falciparum pose a greater challenge than before to the control programs across the world. Specific mutations in the P. falciparum chloroquine resistant transporter gene “ Pfcrt ” have been associated with resistance to not only chloroquine, but also to amodiaquine, one of the artemisinin partners used in Cameroon for the treatment of uncomplicated malaria. We here present data on genetic variation at the Single Nucleotide Polymorphisms (SNPs) level in the Pfcrt gene in five distinct geographical settings of the Southern-Cameroon (the most malaria endemic part), i.e. Ebolowa, Yaounde, Bertoua, Douala and Kye-ossi (a city bordering Cameroon and two others African countries). Two novel mutations, hitherto unreported (in Cameroon) were found in the Pfcrt gene and variable genetic diversity was observed across the populations. High linkage disequilibrium was found between few SNPs including one of the novel mutations suggesting a synergistic work for conferring/maintaining a higher level of resistance. The inference of evolutionary pattern of this gene in Cameroon based on the genetic diversity data depicts a signature of Darwinian positive natural selection on these loci. Observation of novel mutations might traduce new variants in chloroquine/or amodiaquine resistance (proposal awaiting an experimental verification) and signal of positive selection can be the result of drug pressure exerted by misuse of chloroquine (though officially banned from the country) and/or amodiaquine. Our findings thus, provide a baseline understanding of the evolution of a malaria drug resistant gene in Cameroon and suggest a successful establishment of chloroquine-resistant strains which requires urgent attention of the malaria control program in Cameroon. [ABSTRACT FROM AUTHOR]

Abstract Plasmodium vivax resistance to chloroquine (CQ) was first reported over 60 years ago. Here we analyzed sequence variations in the multidrug resistance 1 gene ( Pvmdr1 ), a putative molecular marker for P. vivax CQ resistance, in field isolates collected from three sites in Thailand during 2013–2016. Several single nucleotide polymorphisms previously implicated in reduced CQ sensitivity were found. These genetic variations encode amino acids in the two nucleotide-binding domains as well as the transmembrane domains of the protein. The high level of genetic diversity of Pvmdr1 provides insights into the evolutionary history of this gene. Specifically, there was little evidence of positive selection at amino acid F1076L in global isolates to be promoted as a possible marker for CQ resistance. Population genetic analysis clearly divided the parasites into eastern and western populations, which is consistent with their geographical separation by the central malaria-free area of Thailand. With CQ-primaquine remaining as the frontline treatment for vivax malaria in all regions of Thailand, such a population subdivision could be shaped and affected by the current drugs for P. falciparum since mixed P. falciparum/P. vivax infections often occur in this region. Highlights • Low genetic diversity of Pvmdr1 gene in Thailand • Particular domains of the gene showed high genetic diversity. • The parasites are genetically subdivided into eastern and western populations. • There was action of directional selection in the evolutionary course of Pvmdr1 gene. • The mutant F1076L known as one of the probable markers for CQR was under selection. [ABSTRACT FROM AUTHOR]