Abstract
BackgroundParasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection.ResultsWe have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL) motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization.ConclusionThese results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.
Highlights
Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence
Phylogenetic classification of the RIFIN family An alignment of 134 RIFIN protein sequences from the P. falciparum reference strain 3D7 was analyzed in order to detect divergences within the family
A-type RIFINs are characterized by a total of 10 highly conserved cysteine residues, compared to 6 in Btype variants, 5 of which are common to both sub-types (Fig. 1B grey arrows)
Summary
Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. One important feature of these organisms is that they do not express the whole protein repertoire simultaneously [7,8,9,10] These polymorphic families are predominantly situated in the sub-telomeric ends of chromosomes [2,3,4,5,6], where gene rearrangements are frequent [11,12]. They encode for proteins that presumably fulfill several functions and immune pressure has driven them to antigenically vary at the surface of the infected erythrocyte [13]. Such an accumulation of experimental data is missing for protein families in most parasite species
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