title: The transferrin receptor genes of Trypanosoma equiperdum are less diverse in their transferrin binding site than those of the broad-host range Trypanosoma brucei.
abstract: Trypanosoma brucei and T. equiperdum infect the mammalian bloodstream and tissues. T. brucei is transmitted by tsetse flies between an extremely large range of mammals in sub-Saharan Africa. In contrast, T. equiperdum is restricted to equines, where it is transmitted as a venereal disease. Both species evade immune destruction by changing their variant surface glycoprotein (VSG), encoded in a telomeric VSG expression site. T. brucei has about 20 VSG expression sites, and it has been proposed that their genetic diversity plays a role in host adaptation. Two expression site-associated genes ESAG6 and ESAG7, encode variable transferrin receptor subunits allowing trypanosomes to internalize polymorphic transferrin molecules from different mammals. We investigated if there was a correlation between the size of the trypanosome host range and the degree of ESAG6 genetic diversity. Both T. equiperdum and T. brucei appear to have approximately similar numbers of ESAG6, however, the genetic diversity of the ESAG6 family varies in the two species. We sequenced 114 T. equiperdum ESAG6 genomic clones, resulting in the isolation of 10 T. equiperdum ESAG6 variants. The T. equiperdum ESAG6 genes were less genetically diverse than those of T. brucei in regions known to play a role in transferrin binding. This indicates that ESAG6 genetic diversity playing a role in host adaptation could have been lost in the absence of selection pressure. There was also evidence of positive selection ( d(N) /d(S) = approximately 5) acting on other ESAG6 regions not involved in transferrin binding, perhaps due to antigenic variation of these surface molecules.
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Isobe
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Gloria
authors.initials: G
authors.lastname: Rudenko
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D014644:Genetic Variation; D008969:Molecular Sequence Data; D011990:Receptors, Transferrin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014168:Transferrin / Q000378:metabolism*; D014345:Trypanosoma / Q000235:genetics*
chemical_list: D017931:DNA Primers; D011990:Receptors, Transferrin; D014168:Transferrin