Bioinformatic insights to the ESAG5 and GRESAG5 gene families in kinetoplastid parasites

Abstract

Trypanosoma brucei, the causative agent of African sleeping sickness, evades the immune response by expressing a coat of variant surface glycoprotein (VSG). VSG is expressed from a single telomeric expression site (ES), along with a number of expression site associated genes ( ESAGs). Thus far, the function of most ESAGs is unknown. One ES contains the serum resistance associated gene ( SRA), which confers resistance to trypanosome lytic factor in T. b. rhodesiense. Only three other ESAGs – 5, 6 and 7 – are present in this ES. ESAGs 6 and 7 encode a heterodimeric transferrin receptor, but the function of ESAG5 has not been identified. We present here a bioinformatic analysis of ESAG5 and distinguish between T. brucei-specific ESAGs and Genes Related to ESAG5 ( GRESAGs), which occur outside of ESs in chromosomal-internal contexts. Further, a genome-wide survey of these genes across kinetoplastids identifies a family of GRESAG5s in a number of species. Analysis of phylogenetic relationships indicates that this family may have evolved from a single ancestral copy. Predicted properties of (GR)ESAG5 proteins indicate a glycosylated protein containing either a signal peptide or transmembrane domain. Further analysis indicates a possible relationship to the lipid transfer/lipopolysaccharide-binding family which includes the bactericidal/permeability increasing (BPI) protein. Together, these results provide insights into the structure and evolution of an important extended gene family, and present a number of testable hypotheses which will aid in elucidating the function of ESAG5.