Abstract
BackgroundDomain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila.ResultsIn this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs.ConclusionsThis is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.
Highlights
Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms
To determine protein linkages between a kinetoplastid protozoan species, Trypanosoma brucei, and seven protists representing all major eukaryotic lineages, we used the domain fusion analysis method modified by our in-house software as described in the methods
Trypanosoma brucei TREU927 was used as a reference organism and its complete proteome of 8788 proteins was compared with the proteomes of the seven target species (Table 1), in terms of domain architecture, to identify distant relationships
Summary
Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Proteins exert their diverse functions usually through interactions with other molecules, and often through interactions with other proteins. Apart from direct biochemical analysis to detect protein-protein interactions, an in silico approach is sometimes used to predict protein-protein interactions This fusion analysis ( known as “Rosetta stone” method) takes advantage of the study of genomic structures and sequence similarity to detect putative interacting protein pairs, which, importantly might not have been suspected based on current biochemical knowledge. T. brucei is amenable to genetic manipulation for verification of the results presented here
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