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

Abstract

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.

Genome-Wide Patterns of Genetic Polymorphism and Signatures of Selection in Plasmodium vivax

“…Detailed analyses of the function of this protein and others showing signature of positive selection, like histone deacetylases, could help better understand their specific roles in the adaptation of the parasite to the human host and perhaps open the possibility to identify essential proteins that could serve as targets for treatment. Although intense efforts have been invested in understanding genes encoding antigens putatively under balancing selection to understand the parasite’ evasion of the host immunity ( Escalante et al 2004 ; Chenet et al 2012 ; Krzyczmonik et al 2012 ; Pacheco et al 2012a ), other genes presenting signatures of directional selection such as the putative small GTPase Rab1 could be key regulators of cytoskeleton dynamics and/or been involved in secretory activities ( Jekely 2003 ). Unfortunately, there is no thorough understanding of this and other proteins functions in the Plasmodium cell.…”

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies possible targets of allele-specific immunity to clinical malaria

“…Fifty-five of the genes containing significantly differentiated sites (38%) encode proteins of unknown function that are not associated with any computed or curated molecular function or biological process based on Gene Ontology ( S1 Table ). These 145 gene products included some proteins previously identified as potential vaccine candidates, including AMA1 (apical membrane antigen 1) [ 17 , 20 ], ASP (apical sushi protein, PF3D7_0405900) [ 41 ], CLAG8 (cytoadherence linked asexual protein 8, PF3D7_0831600) [ 42 , 43 ], SLARP (sporozoite and liver asparagine-rich protein, PF3D7_1147000) [ 44 ] and a conserved protein of unknown function (PF3D7_1359000) [ 45 ].…”

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies potential targets of allele-specific immunity to clinical malaria

“…Fifty-five of the genes containing significantly differentiated sites (38%) encode proteins of unknown function that are not associated with any computed or curated molecular function or biological process based on Gene Ontology (Supplementary Table 1). These 145 gene products included some proteins previously identified as potential vaccine candidates, including AMA1 (apical membrane antigen 1) (Takala et al, 2009; Thera et al, 2011, p. 20), ASP (apical sushi protein, PF3D7_0405900) (Vanegas et al, 2014), CLAG8 (cytoadherence linked asexual protein 8, PF3D7_0831600) (Gupta et al, 2015; Iriko et al, 2008), SLARP (sporozoite and liver asparagine-rich protein, PF3D7_1147000) (van Schaijk et al, 2014) and a conserved protein of unknown function (PF3D7_1359000) (Krzyczmonik et al, 2012).…”