Comparative analysis of Trypanosoma brucei gambiense antigen gene family and its potential use in epidemiology of sleeping sickness

Abstract

The identification of African trypanosomes infective for man and the characterization of their repertoire of variable antigen types (VATs) is a major challenge to epidemiologists. The present work, based on previous studies, brings evidence that DNA analysis may provide a molecular approach to these problems. Two cloned cDNAs coding for Trypanosoma brucei brucei variant-specific antigens have been used as probes to evaluate, by hybridization on DNA blots, the relatedness of different trypanosome clone stocks, mainly of T. b. gambiense. It appears that, in all T. b. gambiense stocks, the AnTat 1.8-like gene family produces a typical pattern of bands which is discussed in terms of gene evolution and of possible use as a means to discriminate T. b. gambiense from the other sub-species. A deviation from this common pattern concerns the basic copy of the gene, the presence or absence of which is correlated with the ability of the stocks to express AnTat 1.8 isotypes: this observation suggests that only one member of the AnTat 1.8 DNA sequence family might be involved in the expression of the AnTat 1.8 isotype, and that useful information on serodemes and their VAT repertoires could be obtained from DNA analysis. Among the silent sequences of this family, one appears remarkably similar to the basic copy. Its apparent inability to be expressed could be linked to alterations of the repetitive sequences flanking the transposable element. This observation supports the hypothesis that these repeats are involved in the transposition leading to expression of the gene.