Comparison of genomic signatures of selection on Plasmodium falciparum between different regions of a country with high malaria endemicity

Duffy, Craig W.; Assefa, Samuel; Abugri, James; Amoako, Nicholas; Owusu‐Agyei, Seth; Anyorigiya, Thomas; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Conway, David J.; Awandare, Gordon A.

doi:10.1186/s12864-015-1746-3

Cited by 40 publications

(60 citation statements)

References 52 publications

(16 reference statements)

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“…In particular, all var genes were present in the de novo assembly with all but one having greater than 50% exonic coverage (Figure S1C,D). In spite of the similarities, the Burkina parasites contain approximately 25,000 SNPs genome-wide compared to the Pf3D7 reference strain, which is in agreement with the level of variability expected for field isolates2829. However, these differences were not sufficiently high to affect mapping of sequencing reads of parasites present in Burkina to the 3D7 reference genome.…”

Section: Resultssupporting

confidence: 74%

Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae

Gómez-Díaz¹,

Yerbanga²,

Lefèvre³

et al. 2017

Sci Rep

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P. falciparum phenotypic plasticity is linked to the variant expression of clonal multigene families such as the var genes. We have examined changes in transcription and histone modifications that occur during sporogonic development of P. falciparum in the mosquito host. All var genes are silenced or transcribed at low levels in blood stages (gametocyte/ring) of the parasite in the human host. After infection of mosquitoes, a single var gene is selected for expression in the oocyst, and transcription of this gene increases dramatically in the sporozoite. The same PF3D7_1255200 var gene was activated in 4 different experimental infections. Transcription of this var gene during parasite development in the mosquito correlates with the presence of low levels of H3K9me3 at the binding site for the PF3D7_1466400 AP2 transcription factor. This chromatin state in the sporozoite also correlates with the expression of an antisense long non-coding RNA (lncRNA) that has previously been shown to promote var gene transcription during the intraerythrocytic cycle in vitro. Expression of both the sense protein-coding transcript and the antisense lncRNA increase dramatically in sporozoites. The findings suggest a complex process for the activation of a single particular var gene that involves AP2 transcription factors and lncRNAs.

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Section: Resultssupporting

confidence: 74%

Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae

Gómez-Díaz¹,

Yerbanga²,

Lefèvre³

et al. 2017

Sci Rep

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“…5a). The average F WS value across all infections was 0.87, which is higher (indicating less mixed infections) than seen previously in comparable sequence data from highly endemic African population samples (Auburn et al 2012;Mobegi et al 2014;Duffy et al 2015).…”

Section: Genomewide Analysis Of Plasmodium Falciparum Population Strucontrasting

confidence: 44%

“…Tajima's D values were calculated to assess the allele frequency spectrum for each gene with at least 3 SNPs using custom R scripts as applied to previous population samples (Duffy et al 2015). As there were missing SNP data in subsets of isolates at each gene, isolates were excluded on a per gene basis to retain those with complete data for the analysis of each gene separately.…”

Section: Plasmodium Falciparum Genome Sequencing and Population Genommentioning

confidence: 99%

Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution

Duffy

Ba²,

Assefa

et al. 2017

Molecular Ecology

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To determine whether the major human malaria parasite Plasmodium falciparum exhibits fragmented population structure or local adaptation at the northern limit of its African distribution where the dry Sahel zone meets the Sahara, samples were collected from diverse locations within Mauritania over a range of ~1000 km. Microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and Illumina paired‐end sequences were obtained to yield high coverage genomewide single nucleotide polymorphism (SNP) data for 65 clinical infection samples from four locations. Most infections contained single parasite genotypes, reflecting low rates of transmission and superinfection locally, in contrast to the situation seen in population samples from countries further south. A minority of infections shared related or identical genotypes locally, indicating some repeated transmission of parasite clones without recombination. This caused some multilocus linkage disequilibrium and local divergence, but aside from the effect of repeated genotypes there was minimal differentiation between locations. Several chromosomal regions had elevated integrated haplotype scores (|iHS|) indicating recent selection, including those containing drug resistance genes. A genomewide FST scan comparison with previous sequence data from an area in West Africa with higher infection endemicity indicates that regional gene flow prevents genetic isolation, but revealed allele frequency differentiation at three drug resistance loci and an erythrocyte invasion ligand gene. Contrast of extended haplotype signatures revealed none to be unique to Mauritania. Discrete foci of infection on the edge of the Sahara are genetically highly connected to the wider continental parasite population, and local elimination would be difficult to achieve without very substantial reduction in malaria throughout the region.

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“…However, a closer look at previously published P. falciparum scans for selection in multiple locations in Africa also reveals a role for adaptation through the modification of transcriptional regulation. The P. falciparum ortholog of the SETdomain protein on chromosome 11 (PVX_114585) identified in our nS L analysis lies near the center of a selective sweep that also has occurred in Senegal, the Gambia, and Ghana (16,49,50). In addition, it is known that transcriptional timing can affect P. falciparum drug-resistance responses, in particular to artemisinins (51).…”

Section: Discussionmentioning

confidence: 99%

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Parobek

Lin

Saunders

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivax's resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination.D uring the last decade, western Cambodia has been the focus of numerous and multimodal interventions to control the spread of artemisinin-resistant Plasmodium falciparum (1, 2). Such interventions, including increased vector control, increased surveillance, and improved access to quality artemisinin-combination therapy (ACT), would be expected to curtail coendemic Plasmodium vivax as well. However, even as P. falciparum infections in Cambodia decreased by 81% between 2009 and 2013, P. vivax cases have increased, making it the predominant species in the Mekong region (3-6). This scenario, repeated in Brazil and other areas of coendemicity, has led to growing awareness that P. vivax, although infecting the same populations and transmitted by the same mosquito vectors, will likely be the more challenging species to eradicate (6-9). In this study, we use population genomics to gain insight into the evolutionary factors underlying P. vivax's resilience to malaria control measures.Population genetic studies have previously hinted at the resilience of P. vivax populations in comparison with P. falciparum. Studies of microsatellites and highly variable antigens of sympatric P. vivax and P. falciparum populations in Southeast Asia and the Southwest Pacific have consistently shown P. viv...

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Comparison of genomic signatures of selection on Plasmodium falciparum between different regions of a country with high malaria endemicity

Cited by 40 publications

References 52 publications

Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae

Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae

Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

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