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

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de Oliveira, Thais C. ; Rodrigues, Priscila T. ; Menezes, Maria Jose ; Goncalves-Lopes, Raquel M. ; Bastos, Melissa S. ; Lima, Nathalia F. ; Barbosa, Susana ; Gerber, Alexandra L. ; de Morais, Guilherme Loss ; Berna, Luisa ; Phelan, Jody ; Robello, Carlos ; de Vasconcelos, Ana Tereza R. ; Alves, Joao Marcelo P. ; Ferreira, Marcelo U.

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 11, n. 7 JUL 2017.
• Web of Science Citations: 8

Abstract

Background The 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. Methods We 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/Conclusions We found that New World populations of P. vivax are as diverse (nucleotide diversity p between 5.2 x 10(-4) and 6.2 x 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. (AU)

• FAPESP's process: 13/26928-0 - Mansonella ozzardi: a neglected filaria that may modulate the immune response to co-occurring infections
• Grantee: Nathália Ferreira Lima
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/51835-7 - Chloroquine resistance in Plasmodium vivax: phenotypic and molecular evaluation in Brazilian Western Amazon
• Grantee: Marcelo Urbano Ferreira
• Support type: Regular Research Grants
• FAPESP's process: 13/23770-6 - Optimising malaria case detection in a low transmission setting in rural Brazilian Amazon
• Grantee: Susana Do Carmo Pinto Barbosa
• Support type: Scholarships in Brazil - Post-Doctorate