Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence

Neafsey, Daniel E.; Schaffner, Stephen F.; Volkman, Sarak K.; Park, Daniel; Montgomery, Philip; Milner, Danny A.; Lukens, Amanda K.; Rosen, David; Daniels, Rachel F.; Houde, Nathan; Cortese, Joseph F.; Tyndall, Erin; Gates, Casey; Stange-Thomann, Nicole; Sarr, Ousmane; Ndiaye, Daouda; Ndir, O.; Mboup, S.; Ferreira, Marcelo U.; Moraes, Sandra do Lago; Dash, A. P.; Chitnis, Chetan E.; Wiegand, Roger C.; Hartl, Daniel L.; Birren, Bruce W.; Lander, Eric S.; Sabeti, Pardis C.; Wirth, Dyann F.

doi:10.1186/gb-2008-9-12-r171

Cited by 117 publications

(126 citation statements)

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“…The trend towards a negative correlation between levels of genetic diversity and malaria transmission contrasts with the pattern observed for P. falciparum , for which highest diversity is seen in high-transmission settings [8,15]. This contrast is surprising and may reflect differences in the demographic history and biology of these major human parasites.…”

Section: Resultsmentioning

confidence: 82%

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

et al. 2010

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BackgroundThe ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized.ResultsWe examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance.ConclusionThese findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.See commentary: http://www.biomedcentral.com/1741-7007/8/90

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Section: Resultsmentioning

confidence: 82%

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

et al. 2010

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“…We will call it here the "starving sex hypothesis". It has been accepted by many authors in order to account for the observed population structure of Plasmodium (Arnott et al, 2012;Branch et al, 2011;Chenet et al, 2012;Conway, 2007;Ferreira et al, 2007;Gupta et al, 2012;Imwong et al, 2006Imwong et al, , 2007Iwagami et al, 2009;Mobegi et al, 2012;Mu et al, 2005;Mzilahowa et al, 2007;Neafsey, 2013;Neafsey et al, 2008;Nkhoma et al, 2013;Schultz et al, 2010;Volkman et al, 2012a,b). It can be challenged, as we will further see, since many observations are at odds with it, both in P. falciparum and in Plasmodium vivax.…”

Section: Population Structure Of Plasmodium Andmentioning

confidence: 99%

New Insights into Clonality and Panmixia in Plasmodium and Toxoplasma

Tibayrenc¹,

Ayala²

2014

Advances in Parasitology

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“…Research has revealed that recombination rates are variable for P. falciparum strains and achieve the highest values for African strains (Mu et al, 2005). It was also observed that genes related to immunity are under stronger diversifying selection when compared to other genes as they have higher pN/pS ratio (Jeffares et al, 2007;Neafsey et al, 2008). Identification and characterization of such genes may be crucial for better understanding of the disease, its different clinical manifestations and potential resistance to vaccination (Richie and Saul, 2002).…”

Section: Introductionmentioning

confidence: 99%

Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

Krzyczmonik

Świtnicki

Kaczanowski

2012

Infection, Genetics and Evolution

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It was observed that pressure of host immune system leads to diversifying selection (which can be measured in terms of pN/pS ratio). In this research we checked whether Plasmodium falciparum proteins containing experimentally evident epitopes from the IEDB database are subject to diversifying selection. We also investigated which life stage of this parasite and which proteins are subject to the strongest immune pressure. To answer these questions we used information about experimentally evident epitopes from Plasmodium, that interact with human immune system and sequences of different isolates of P. falciparum.We confirmed the expectations that proteins containing IEDB epitopes are subject to stronger diversifying selection which is evidenced by higher pN/pS ratio. A stage characterized by the highest average pN/pS ratio is that of the sporozoite. The greatest fraction of putative antigens is also present at this stage. We also found that the sporozoite stage is particularly interesting for further analysis as it potentially contains the highest number of unidentified epitopes.

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Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence

Abstract: An array-based SNP genotyping platform for Plasmodium falciparum is reported together with an analysis of SNP diversity in global population samples.

Cited by 117 publications

References 35 publications

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

New Insights into Clonality and Panmixia in Plasmodium and Toxoplasma

Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

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