Dataset Information

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

ABSTRACT: The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

SUBMITTER: Carlton JM

PROVIDER: S-EPMC2651158 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

Carlton Jane M JM Adams John H JH Silva Joana C JC Bidwell Shelby L SL Lorenzi Hernan H Caler Elisabet E Crabtree Jonathan J Angiuoli Samuel V SV Merino Emilio F EF Amedeo Paolo P Cheng Qin Q Coulson Richard M R RM Crabb Brendan S BS Del Portillo Hernando A HA Essien Kobby K Feldblyum Tamara V TV Fernandez-Becerra Carmen C Gilson Paul R PR Gueye Amy H AH Guo Xiang X Kang'a Simon S Kooij Taco W A TW Korsinczky Michael M Meyer Esmeralda V-S EV Nene Vish V Paulsen Ian I White Owen O Ralph Stuart A SA Ren Qinghu Q Sargeant Tobias J TJ Salzberg Steven L SL Stoeckert Christian J CJ Sullivan Steven A SA Yamamoto Marcio M MM Hoffman Stephen L SL Wortman Jennifer R JR Gardner Malcolm J MJ Galinski Mary R MR Barnwell John W JW Fraser-Liggett Claire M CM

Nature 20081001 7214

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vi ...[more]

PMID: 18843361

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Project description: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.

Project description:BackgroundThe distributions of incubation and relapse periods are key components of infectious disease models for the malaria parasite Plasmodium vivax; however, detailed distributions based upon experimental data are lacking.MethodsUsing a range of historical, experimental mosquito-transmitted human infections, Bayesian estimation with non-informative priors was used to determine parametric distributions that can be readily implemented for the incubation period and time-to-first relapse in P. vivax infections, including global subregions by parasite source. These analyses were complemented with a pooled analysis of observational human infection data with infections that included malaria chemoprophylaxis and long-latencies. The epidemiological impact of these distributional assumptions was explored using stochastic epidemic simulations at a fixed reproductive number while varying the underlying distribution of incubation periods.ResultsUsing the Deviance Information Criteria to compare parameterizations, experimental incubation periods are most closely modeled with a shifted log-logistic distribution; a log-logistic mixture is the best fit for incubations in observational studies. The mixture Gompertz distribution was the best fit for experimental times-to-relapse among the tested parameterizations, with some variation by geographic subregions. Simulations suggest underlying distributional assumptions have critically important impacts on both the time-scale and total case counts within epidemics.ConclusionsThese results suggest that the exponential and gamma distributions commonly used for modeling incubation periods and relapse times inadequately capture the complexity in the distributions of event times in P. vivax malaria infections. In future models, log-logistic and Gompertz distributions should be utilized for general incubation periods and relapse times respectively, and region-specific distributions should be considered to accurately model and predict the epidemiology of this important human pathogen.

Dataset Information

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

Publications

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

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