Microsatellite polymorphism within pfcrt provides evidence of continuing evolution of chloroquine-resistant alleles in Papua New Guinea

• Published in: Malaria Journal
• Main Authors: Sharma Yagya D, Reeder John, Mueller Ivo, Michon Pascal, Mehlotra Rajeev K, DaRe Jeana T, Stoneking Mark, Zimmerman Peter A
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2007
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-6-34; https://doaj.org/article/02de1a4485264672bf1ed7e78f341a81

Abstract Background Polymorphism in the pfcrt gene underlies Plasmodium falciparum chloroquine resistance (CQR), as sensitive strains consistently carry lysine (K), while CQR strains carry threonine (T) at the codon 76. Previous studies have shown that microsatellite (MS) haplotype variation can be used to study the evolution of CQR polymorphism and to characterize intra- and inter-population dispersal of CQR in Papua New Guinea (PNG). Methods Here, following identification of new polymorphic MS in introns 2 and 3 within the pfcrt gene (msint2 and msint3, respectively), locus-by-locus and haplotype heterozygosity ( H ) analyses were performed to determine the distribution of this intronic polymorphism among pfcrt chloroquine-sensitive and CQR alleles. Results For MS flanking the pfcrt CQR allele, H ranged from 0.07 (B5M77, -18 kb) to 0.094 (9B12, +2 kb) suggesting that CQ selection pressure was responsible for strong homogenisation of this gene locus. In a survey of 206 pfcrt -SVMNT allele-containing field samples from malaria-endemic regions of PNG, H for msint2 was 0.201. This observation suggests that pfcrt msint2 exhibits a higher level of diversity than what is expected from the analyses of pfcrt flanking MS. Further analyses showed that one of the three haplotypes present in the early 1980's samples has become the predominant haplotype (frequency = 0.901) in CQR parasite populations collected after 1995 from three PNG sites, when CQR had spread throughout malaria-endemic regions of PNG. Apparent localized diversification of pfcrt haplotypes at each site was also observed among samples collected after 1995, where minor CQR-associated haplotypes were found to be unique to each site. Conclusion In this study, a higher level of diversity at MS loci within the pfcrt gene was observed when compared with the level of diversity at pfcrt flanking MS. While pfcrt (K76T) and its immediate flanking region indicate homogenisation in PNG CQR parasite populations, pfcrt intronic MS variation provides evidence that the ...