Article Figures & Data
Figures
- FIG 1
Alignment of the Plasmodium K13 kelch propeller domain. The Pfk13 mutations that have been associated with clinical delayed parasite clearance (2) are shown. The five mutations validated in vivo and in vitro are indicated with an asterisk. The Haemoproteus tartakovskyi (an avian haemosporidian parasite) k13 gene was included as an outgroup.
- FIG 2
Bayesian phylogenetic hypothesis of Plasmodium parasites based on the k13 gene (42 sequences; 1,985 bp, excluding gaps). The values at the nodes are posterior probabilities (see Materials and Methods). Haemoproteus tartakovskyi (an avian haemosporidian parasite) k13 gene was included as an outgroup.
- FIG 3
Relative evolutionary rates of the Plasmodium k13 gene. Branches are colored from high (green) to low (purple) according to their relative rates with respect to the rate at the root, which was set to 1, as estimated by RelTime without calibration constraints.
- FIG 4
Median-joining network of the P. falciparum k13 haplotypes. (A) Median-joining network of the P. falciparum k13 haplotypes using 982 cosmopolitan complete sequences. All the k13 gene sequences obtained here for P. falciparum population samples (n = 463), as well as those available in the PlasmoDB and NCBI databases (n = 519), were included. Branch lengths are proportional to divergence; node sizes are proportional to the total haplotype frequencies. The network shows 147 haplotypes found in 982 sequences with a haplotype diversity (Hd) of 0.742 (SD = 0.012). Every color corresponds to a different geographic origin. Lines separating haplotypes represent mutational steps. The four most frequent haplotypes are indicated. (B) Frequencies of candidate/validated mutations in the propeller domain of the Pfk13 gene that have been associated with clinical delayed parasite clearance by country (Table 2). Frequencies were estimated using an alignment constructed with 3,916 partial (n = 2,934) and complete (n = 982) k13 gene sequences. C-M, China-Myanmar.
Tables
- TABLE 1
Polymorphism found in k13 gene of Plasmodium falciparum
Continent π (SE) dS dN dN − dS (SEa) P value (Z-statistic),b hypothesis testing result S Tajima’s D (P value) No. of haplotypes (Hd) Asia (n = 321) 0.0004 (0.0002) 5.77E−05 0.0005 0.0004 (0.0002) 0.021 (2.338), dN > dS 32 −2.268 (<0.01) 30 (0.663) Africa (n = 411) 0.0006 (0.0003) 0.0004 0.0005 0.0002 (0.0003) 0.552 (0.597), dN = dS 85 −2.654 (<0.001) 86 (0.747) Americas (n = 128) 0.0003 (0.0002) 0.0006 0.0002 −0.0004 (0.0003) 0.271 (−1.107), dN = dS 19 −2.306 (<0.01) 16 (0.469) Total (n = 982) 0.0005 (0.0002) 0.0003 0.0006 −0.0003 (0.0003) 0.317 (1.006), dN = dS 146 −2.676 (<0.001) 147 (0.742) - TABLE 2
Number of Pfk13 sequences with mutations (candidates/validated) associated with clinical delayed parasite clearance (per codon and per country)a
Country No. of CDS No. of sequences inside propeller domain (codons 440 to 680) with: Compl. Partial Total P441L F446I G449A N458Y Y493H N537D G538V R539T I543T P553L R561H V568G P574L C580Y A675V Kenya 14 405 419 0 0 0 0 0 0 0 0 0 0 1 4 0 0 0 Mali 23 213 236 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Nigeria 29 27 56 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Cambodia 2 5 7 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 China 0 329 329 0 119 0 1 0 0 0 0 0 5 1 0 16 2 0 China-Myanmar border 57 0 57 0 28 0 1 0 0 0 1 0 0 0 0 3 0 0 India 0 140 140 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Myanmar 0 43 43 1 0 1 1 0 0 1 1 0 2 1 0 1 3 1 Thailand 260 973 1,233 8 12 10 11 9 0 6 14 0 0 21 0 63 298 0 Papua New Guinea 0 7 7 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Total 385 2,142 2,527 9 161 11 14 9 0 7 16 0 7 25 4 83 306 2 ↵a The total number of complete (Compl.) and partial sequences obtained from the databases (PlasmoDB and NCBI) are shown. CDS, coding sequences.
Supplemental material
- Supplemental file 1 -
Supplemental Data Sets S1 to S6
XLSX, 1.1M
- Supplemental file 1 -
