Unraveling CAF-1 family in Plasmodium falciparum: comparative genome-wide identification and phylogenetic analysis among eukaryotes, expression profiling and protein-protein interaction studies.

Abstract

The present research reports a detailed in silico analysis of chromatin assembly factor-1 (CAF-1) family in human malaria parasite Plasmodium falciparum. Our analysis revealed five chromatin assembly factor-1 genes in P. falciparum (PfCAF-1) and the PfCAF-1 family was divided into two classes where, Class A belongs to the CAF-1 complex and others are kept in Class B. For comparative studies, orthologs of PfCAF-1 family were identified across 53 eukaryotic species and evolutionary relationships were drawn for different CAF-1 subfamilies. The phylogenetic analysis revealed grouping of evolutionary-related species together, although, divergence was observed in branching pattern. A detailed analysis of domain composition highlighted species-specific features viz. species-specific KDDS repeats of 84 amino acids were identified in PfCAF-1A whereas, members of CAF-1C/RbAp48 and RbAp46 subfamily exhibited least variation in size and domain composition. The qRT-PCR analysis revealed upregulation of PfCAF-1 members in trophozoite or schizont stage. Furthermore, a comparative expression analysis of the available transcriptome and proteome data along with qRT-PCR analysis revealed mixed expression patterns (coordination as well as non-coordination between different studies). Protein-protein interaction network analyses of PfCAF-1 family were carried out highlighting important complexes based on interologs. The PfRbAp48 was found to be highly connected with a total of 108 PPIs followed by PfRbAp46. The results unravel insights into the PfCAF-1 family and identify unique features, thus opening new perspectives for further targeted developments to understand and combat malaria menace.