Abstract
BackgroundMany parasites use multicopy protein families to avoid their host's immune system through a strategy called antigenic variation. RIFIN and STEVOR proteins are variable surface antigens uniquely found in the malaria parasites Plasmodium falciparum and P. reichenowi. Although these two protein families are different, they have more similarity to each other than to any other proteins described to date. As a result, they have been grouped together in one Pfam domain. However, a recent study has described the sub-division of the RIFIN protein family into several functionally distinct groups. These sub-groups require phylogenetic analysis to sort out, which is not practical for large-scale projects, such as the sequencing of patient isolates and meta-genomic analysis.ResultsWe have manually curated the rif and stevor gene repertoires of two Plasmodium falciparum genomes, isolates DD2 and HB3. We have identified 25% of mis-annotated and ~30 missing rif and stevor genes. Using these data sets, as well as sequences from the well curated reference genome (isolate 3D7) and field isolate data from Uniprot, we have developed a tool named RSpred. The tool, based on a set of hidden Markov models and an evaluation program, automatically identifies STEVOR and RIFIN sequences as well as the sub-groups: A-RIFIN, B-RIFIN, B1-RIFIN and B2-RIFIN. In addition to these groups, we distinguish a small subset of STEVOR proteins that we named STEVOR-like, as they either differ remarkably from typical STEVOR proteins or are too fragmented to reach a high enough score. When compared to Pfam and TIGRFAMs, RSpred proves to be a more robust and more sensitive method. We have applied RSpred to the proteomes of several P. falciparum strains, P. reichenowi, P. vivax, P. knowlesi and the rodent malaria species. All groups were found in the P. falciparum strains, and also in the P. reichenowi parasite, whereas none were predicted in the other species.ConclusionsWe have generated a tool for the sorting of RIFIN and STEVOR proteins, large antigenic variant protein groups, into homogeneous sub-families. Assigning functions to such protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. RSpred removes the need for complicated and time consuming phylogenetic analysis methods. It will benefit both research groups sequencing whole genomes as well as others working with field isolates. RSpred is freely accessible via http://www.ifm.liu.se/bioinfo/.
Highlights
Many parasites use multicopy protein families to avoid their host’s immune system through a strategy called antigenic variation
The RIFIN and STEVOR families are groups of Variable Surface Antigens (VSA) proteins that are unique to the Plasmodium falciparum and P. reichenowi parasites [4,5,6,7,8,9]
A recent analysis of the whole rif gene repertoire, which encode for RIFIN proteins, from the reference genome has concluded that this family can be subdivided into functionally distinct groups [12]
Summary
Many parasites use multicopy protein families to avoid their host’s immune system through a strategy called antigenic variation. RIFIN and STEVOR proteins are variable surface antigens uniquely found in the malaria parasites Plasmodium falciparum and P. reichenowi These two protein families are different, they have more similarity to each other than to any other proteins described to date. A recent analysis of the whole rif gene repertoire, which encode for RIFIN proteins, from the reference genome has concluded that this family can be subdivided into functionally distinct groups [12]. One of these sub-groups, A-RIFIN, as well as the STEVOR proteins are predominantly exposed to the host’s immune system at the surface of the infected red blood cell (RBC) [4,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
