Article Figures & Data
Figures
- FIG 1
2D representation of PfMRP2, with the location of the analyzed SNPs and microindels. The structure depicted refers to the reference P. falciparum 3D7 clone sequence, comprising 2,108 aa. Note that the numbering of amino acids follows the 3D7 reference genomic data, independently of the microindel variation observed in the studied Thai set of parasites.
- FIG 2
Microindels identified in the Pfmrp2 by sequencing the Thai isolates and aligning the sequences with publicly available sequencing data. The 5 microindels identified were subcategorized as MI variants of type a (the 3D7 reference genomic sequence type); the other types are designated b to l for the variants found among the Thai isolates (N) and the publicly available genomes. Symbols for publicly available genomes: £, Dd2; &, Hb3; #, UGT5.1; §, RAJ116; +, IGH-CR14. Highlighted black boxes denote amino acid positions that are described in the PlasmoDB database (http://www.plasmodb.org) as single nucleotide polymorphisms.
- FIG 3
SNPs and microindels and their associations with IC50 values and parasite clearance rates. We used one-way ANOVA to compare associations between IC50s and the presence (+) or absence (−) of the SNP or microindel type. Chi-square analysis was used to compare associations between high (<36-h) or low (>90-h) parasite clearance rates and the presence (+) or absence (−) of the SNP or microindel type. *, P < 0.05 (significant findings are also highlighted in gray, for additional emphasis. #, the number of samples bearing each genotype. Results represent only the analysis for genotypes with allele frequencies of >8%.
Tables
- TABLE 1
Membrane-spanning domains and transmembrane predictions for PfMRP2
MSD TM Predicted TM domaina (aa span) based on: Previously published (13) OCTOPUS TMHMM O/T merged MSD1 1 133–155 133–157 132–155 134–155 2 180–202 178–199 180–203 180–199 3 402–424 401–422 396–418 401–418 4 434–456 425–449 428–454 428–448 5 517–539 511–531 511–533 512–531 6 554–575 544–564 548–565 551–562 — 787–807 — — MSD2 7 — 1397–1419 1398–1426 1400–1417 8 1430–1452 1445–1472 1446–1471 1448–1470 1473–1495 — 1485–1506 — 9 1510–1532 1524–1545 1526–1546 1528–1545 10 1553–1570 1547–1564 1547–1565 1547–1564 11 1574–1593 1629–1658 1629–1651 1631–1651 12 1654–1676 1667–1689 1671–1693 1671–1689 ↵a The TM segments shown are those reported from a previous study (13) or predicted in this study by using the OCTOPUS and TMHMM software. To obtain a reliable model, we supported the information for the TM segments obtained by merging the OCTOPUS/TMHMM probabilities (i.e., data in the O/T merged column). TM domain amino acid ranges shown in bold had the greatest differences from the data obtained from reference 13 or via analysis using the OCTOPUS and TMHMM software programs. TM column represents the transmembrane number for the O/T merged model. Dashes (—) represent TM segments.
- TABLE 2
SNPs identified in Pfmrp2 by sequencing the Thai isolates
Chromosome positiona Nucleotide position Nucleotide change Amino acid position Amino acid change Frequency (proportion) Location 1198644 561 T → A 187 Synonymous 0.02 (1/46) TM2 1198610*# 595 C → G 199 L → V 1.00 (46/46) TM2 1198321 884 C → G 295 T → R 0.02 (1/46) loop 1198275 930 G → T 310 L → F 0.02 (1/46) loop 1198224 981 C → T 327 Synonymous 0.02 (1/46) loop 1197428*§ 1777 A → G 593 N → D 0.07 (3/46) NBD1 1197341* 1864 A → G 622 N → D 0.22 (10/46) NBD1 1197064*§# 2141 A → T 714 K → I 1.00 (46/46) NBD1 1196808*§ 2397 C → T 799 Synonymous 0.39 (16/41) NBD1 1195791*§ 3414 T → C 1138 Synonymous 0.20 (9/44) NBD1 1194626*# 4579 T → A 1527 S → T 1.00 (46/46) TM9 1194614*# 4591 C → A 1531 L → I 1.00 (46/46) TM9 1194093 5112 T → C 1704 Synonymous 0.02 (1/46) NBD2 1193954 5251 A → T 1751 N → Y 0.09 (3/34) NBD2 1193947§ 5258 T → C 1753 F → S 0.07 (3/46) NBD2 1193882 5323 A → G 1775 I → V 0.14 (5/36) NBD2 1193861 5344 A → T 1782 M → L 0.02 (1/46) NBD2 1193820 5385 A → T 1795 Synonymous 0.08 (3/37) NBD2 ↵a Symbols: *, SNP previously registered with PlasmoDB; §, SNP previously found by deep sequencing of 227 samples from Africa, Asia, and Oceania (30); #, SNP previously described in reference 31.
Supplemental material
Files in this Data Supplement:
- Supplemental file 1 -
Supplemental Figure S1: transmembrane probability of PfMRP2 2D structure. Table S1: oligonucleotide primer sequences.
PDF, 137K
- Supplemental file 1 -
