Single-nucleotide polymorphisms and genome diversity in Plasmodium vivax

Abstract

The study of genetic variation in malaria parasites has practical significance for developing strategies to control the disease. Vaccines based on highly polymorphic antigens may be confounded by allelic restriction of the host immune response. In response to drug pressure, a highly plastic genome may generate resistant mutants more easily than a monomorphic one. Additionally, the study of the distribution of genomic polymorphisms may provide information leading to the identification of genes associated with traits such as parasite development and drug resistance. Indeed, the age and diversity of the human malaria parasite Plasmodium falciparum has been the subject of recent debate, because an ancient parasite with a complex genome is expected to present greater challenges for drug and vaccine development. The genome diversity of the important human pathogen Plasmodium vivax, however, remains essentially unknown. Here we analyze an approximately 100-kb contiguous chromosome segment from five isolates, revealing 191 single-nucleotide polymorphisms (SNPs) and 44 size polymorphisms. The SNPs are not evenly distributed across the segment with blocks of high and low diversity. Whereas the majority (approximately 63%) of the SNPs are in intergenic regions, introns contain significantly less SNPs than intergenic sequences. Polymorphic tandem repeats are abundant and are more uniformly distributed at a frequency of about one polymorphic tandem repeat per 3 kb. These data show that P. vivax has a highly diverse genome, and provide useful information for further understanding the genome diversity of the parasite.

Fig. 1.

SNP distribution, nucleotide diversity, base composition, and SNP haplotypes of a 100-kb P. vivax chromosomal segment. (A) A physical map integrated with SNPs and polymorphic TRs. Vertical lines above the thick horizontal chromosome line represent SNPs (green, noncoding; purple, synonymous; black, nonsynonymous); vertical lines below the chromosome line represent polymorphic TRs (long lines) or simple sequence repeats (short lines). Gene annotation and gene identification numbers are according to Tchavtchitch et al. (9). Filled red and black rectangles above and below the thin horizontal line represent gene models on the Watson and Crick strands, respectively. (B) Nucleotide diversity with sliding window size of 500 bp, obtained by using DNASP 3.99. (C) GC content plotted along the DNA segment with a window size of 50 bases. (D) SNP haplotypes for the five P. vivax isolates. Blue, G; green, A; red, T; yellow, C. Conserved haplotype blocks are marked with black bars.