Genome-Wide Analysis of Genetic Diversity in Plasmodium falciparum Isolates From China-Myanmar Border

Abstract

Plasmodium falciparum isolates from China-Myanmar border (CMB) have experienced regional special selective pressures and adaptive evolution. However, the genomes of P. falciparum isolates from this region to date are poorly characterized. Herein, we performed whole-genome sequencing of 34 P. falciparum isolates from CMB and a series of genome-wide sequence analyses to reveal their genetic diversity, population structures, and comparisons with the isolates from other epidemic regions (Thai-Cambodia border, Thai-Myanmar border, and West Africa). Totally 59,720 high-quality single-nucleotide polymorphisms (SNPs) were identified in the P. falciparum isolates from CMB, with average nucleotide diversity (π = 4.59 × 10^-4) and LD decay (132 bp). The Tajima's D and Fu and Li's D values of the CMB isolates were -0.8 (p < 0.05) and -0.84 (p < 0.05), respectively, suggesting a demographic history of recent population expansion or purifying selection. Moreover, 78 genes of the parasite were identified that could be under positive selection, including those genes conferring drug resistance such as pfubp1. In addition, 33 SNPs were identified for tracing the source of the parasites with a high accuracy by analysis of the most differential SNPs among the four epidemic regions. Collectively, our data demonstrated high diversity of the CMB isolates' genomes forming a distinct population, and the identification of 33-SNP barcode provides a valuable surveillance of parasite migration among the regions.

Keywords: China–Myanmar border; Plasmodium falciparum; diversity; genetic marker; genomes.

Figure 1

The top |iHS| hits in isolates from China–Myanmar border. X axis is chromosomes 1 to 14 in alternating colors; y axis is the value of |iHS|. The loci above the blue horizontal lines have the top 1% of |iHS| values.

Figure 2

Linkage disequilibrium (LD) decay in four regions. LD decay was measured by r ² between pairs of markers with MAF >2% and within 1,000 bp.

Figure 3

Population structure in the sample set analyzed. (A–C) Principal component analysis (A), a neighbor-joining tree (B) and an admixture analysis (C). Principal component analysis identified the four groups clearly. The neighbor-joining tree has four distinct branches separating four major components of population structure that correspond to the four geographical groups of sample; samples from WAF are separated from TCB, TMB, and CMB by long branches. Admixture analysis distinguished these four major components according to an optimized cluster value of K = 6, and multiple parasite subpopulations were found in TCB. WAF, West Africa; TCB, Thai–Cambodia border; TMB, Thai–Myanmar border; CMB, China–Myanmar border.

Figure 4

The top |XPEHH| hits for WAF, TCB, and TMB, using CMB as reference. X axis is chromosomes 1 to 14 in alternating colors; y axis is the value of |XPEHH|. The loci above the blue horizontal lines have the top 1% of |XPEHH| values; vertical lines represent the chromosome locations of three genes detected across the isolates from the other three regions (WAF, TCB, and TMB).