title: Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family.
abstract: BACKGROUND
  Parasitic 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Microbiology, Tumor and Cell biology (MTC), Karolinska Institutet, SE-17177 Stockholm, Sweden and Swedish Institute for Infectious Diseases Control, SE-17182 Stockholm, Sweden. nicolas.joannin@ki.se
authors.forename: Nicolas
authors.initials: N
authors.lastname: Joannin
authors.forename: Saraswathi
authors.initials: S
authors.lastname: Abhiman
authors.forename: Erik L
authors.initials: EL
authors.lastname: Sonnhammer
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation / Q000276:immunology; D000953:Antigens, Protozoan / Q000145:classification* / Q000235:genetics; D017125:Genes, Protozoan; D018503:Genome, Protozoan; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000145:classification* / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins