Dataset Information

Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.

ABSTRACT: Despite a significant drop in malaria deaths during the past decade, malaria continues to be one of the biggest health problems around the globe. WD40 repeats (WDRs) containing proteins comprise one of the largest and functionally diverse protein superfamily in eukaryotes, acting as scaffolds for assembling large protein complexes. In the present study, we report an extensive in silico analysis of the WDR gene family in human malaria parasite Plasmodium falciparum. Our genome-wide identification has revealed 80 putative WDR genes in P. falciparum (PfWDRs). Five distinct domain compositions were discovered in Plasmodium as compared to the human host. Notably, 31 PfWDRs were annotated/re-annotated on the basis of their orthologs in other species. Interestingly, most PfWDRs were larger as compared to their human homologs highlighting the presence of parasite-specific insertions. Fifteen PfWDRs appeared specific to the Plasmodium with no assigned orthologs. Expression profiling of PfWDRs revealed a mixture of linear and nonlinear relationships between transcriptome and proteome, and only nine PfWDRs were found to be stage-specific. Homology modeling identified conservation of major binding sites in PfCAF-1 and PfRACK. Protein-protein interaction network analyses suggested that PfWDRs are highly connected proteins with ~1928 potential interactions, supporting their role as hubs in cellular networks. The present study highlights the roles and relevance of the WDR family in P. falciparum, and identifies unique features that lay a foundation for further experimental dissection of PfWDRs.

SUBMITTER: Chahar P

PROVIDER: S-EPMC4456382 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.

Chahar Priyanka P Kaushik Manjeri M Gill Sarvajeet Singh SS Gakhar Surendra Kumar SK Gopalan Natrajan N Datt Manish M Sharma Amit A Gill Ritu R

PloS one 20150604 6

Despite a significant drop in malaria deaths during the past decade, malaria continues to be one of the biggest health problems around the globe. WD40 repeats (WDRs) containing proteins comprise one of the largest and functionally diverse protein superfamily in eukaryotes, acting as scaffolds for assembling large protein complexes. In the present study, we report an extensive in silico analysis of the WDR gene family in human malaria parasite Plasmodium falciparum. Our genome-wide identification ...[more]

PMID: 26043001

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Project description:BACKGROUND:Plasmodium falciparum shares its most recent common ancestor with parasites found in African apes; these species constitute the so-called Laverania clade. In this investigation, the evolutionary history of Plasmodium lineages found in chimpanzees (Pan troglodytes) was explored. METHODS:Here, the remainders of 74 blood samples collected as part of the chimpanzees' routine health examinations were studied. For all positive samples with parasite lineages belonging to the Laverania clade, the complete mitochondrial genome (mtDNA), the gene encoding dihydrofolate reductase-thymidylate synthase (dhfr-ts), the chloroquine resistance transporter (Pfcrt), the circumsporozoite protein (csp), merozoite surface protein 2 (msp2), and the DBL-1 domain from var2CSA were amplified, cloned, and sequenced. Other Plasmodium species were included in the mtDNA, dhfr-ts, and csp analyses. Phylogenetic and evolutionary genetic analyses were performed, including molecular clock analyses on the mtDNA. RESULTS/CONCLUSIONS:Nine chimpanzees were malaria positive (12.2%); four of those infections were identified as P. falciparum, two as a Plasmodium reichenowi-like parasite or Plasmodium sp., one as Plasmodium gaboni, and two as Plasmodium malariae. All P. falciparum isolates were resistant to chloroquine indicating that the chimpanzees acquired such infections from humans in recent times. Such findings, however, are not sufficient for implicating chimpanzees as an animal reservoir for P. falciparum.Timing estimates support that the Laverania clade has co-existed with hominids for a long-period of time. The proposed species P. gaboni, Plasmodium billbrayi, and Plasmodium billcollinsi are monophyletic groups supporting that they are indeed different species.An expanded CSP phylogeny is presented, including all the Laverania species and other malarial parasites. Contrasting with other Plasmodium, the Laverania csp exhibits great conservation at the central tandem repeat region. Msp2 and var2CSA, however, show extended recent polymorphism in P. falciparum that likely originated after the P. reichenowi-P. falciparum split. The accumulation of such diversity may indicate adaptation to the human host. These examples support the notion that comparative approaches among P. falciparum and its related species will be of great value in understanding the evolution of proteins that are important in parasite invasion of the human red blood cell, as well as those involved in malaria pathogenesis.

Dataset Information

Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.

Publications

Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.

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