Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax

Abstract

BackgroundThe Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax.MethodsWe used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19).Principal findings/ConclusionsWe found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10−4 and 6.2 × 10−4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically diverse sites. Further genome-wide analyses are required to test the demographic scenario suggested by our data.

Whole Genome Sequencing ofPlasmodium vivaxIsolates Reveals Frequent Sequence and Structural Polymorphisms in Erythrocyte Binding Genes

“…Across the genome, the total number of SNPs observed among 44 P. vivax isolates in Ethiopia were comparable to those previously reported in South American [77] and Southeast Asian countries [19]. For instance, 303,616 high-quality SNPs were detected in 228 P. vivax isolates from Southeast Asia and Oceania in a previous study, of which Sal-I was used as the reference sequence and subtelomeric regions were discarded [19].…”

Population genomic evidence of a Southeast Asian origin ofPlasmodium vivax

“…To provide a worldwide comparative study of the P. vivax genetic diversity, population structure and evolution, we performed a large literature search to identify previously published genomic data set. We identified and collected fastq files from 1,134 P. vivax isolates obtained from the following 12 different bioprojects: PRJEB10888 ( 14 ), PRJEB2140 ( 12 ), PRJNA175266 ( 54 ), PRJNA240356 ( 13 ), PRJNA240452, PRJNA240531, PRJNA271480 ( 13 ), PRJNA284437 ( 55 ), PRJNA350554 ( 56 ), PRJNA432819 ( 57 ), PRJNA432819 ( 58 ), PRJNA65119 ( 59 ). In addition, 17 P. vivax-like sequenced genomes from Cameroon, Ivory Coast and Gabon were collected from two different bioprojects (PRJNA474492 and PRJEB2579) ( 23, 25 ).…”

Enhanced Ex Vivo Plasmodium vivax Intraerythrocytic Enrichment and Maturation for Rapid and Sensitive Parasite Growth Assays

“…Parasite sample collection. Brazilian P. vivax samples were collected with protocols described elsewhere, but in the town of Mâncio Lima, Acre State (30), the collections were performed in the context of a randomized, open-label clinical trial (NCT02691910). Indian P. vivax samples were collected with similar protocols but using CF11 columns for leukodepletion, essentially as described previously (31).…”

“…Next, 1.080 g/ml KCl Percoll was made by mixing 100% KCl Percoll with the dilution buffer at a ratio of 64.03% to 35.97%, and the density was verified at ambient temperature using a DMA 35 portable density meter (Anton Paar, Graz, Austria). Cryopreserved parasites were thawed as reported previously (30). Samples (0.100 l to 1500 l) of packed parasitized blood were resuspended to 3 ml using incomplete Iscove's modified Dulbecco's medium (IMDM) and layered on 3 ml of 1.080 g/ml KCl Percoll at ambient temperature in a 15-ml conical tube.…”