Molecular fusion events in carcinogenic organisms: a bioinformatics study for the detection of fused proteins between viruses, bacteria and eukaryotes

Abstract

Molecular fusion events have a prominent role in the initial steps of carcinogenesis. In this study, a bioinformatics analysis was performed between four organisms that are known to induce cancer development in humans: two viruses, Human Herpesvirus 4, and Human T-cell leukaemia virus, one bacterium, Helicobacter Pylori, and one trematode, Schistosoma mansoni. The annotated proteomes from these organisms were analysed using the SAFE software to identify protein fusion events, which may provide insight into protein function similarities and possible merging events during the course of evolution. Based on the results, five fused proteins with very similar functions were detected, whereas proteins with different functions that might act in the same molecular complex or biochemical pathway were not found. Thus, this study analysed the above four well-known cancer-related organisms with de novo bioinformatics programs and provided useful information on protein fusion events, hopefully leading to deeper understanding of carcinogenenesis.

Figure 1.

SAFE software, the main algorithm steps.

Figure 2.

Graphical representation of the discovered fusion events, that passed the unique cutoff filter, recuperated from the SAFE software. (A) The fusion event detected leading to a cell division control protein 48 from the AAA family in Schistosoma mansoni, containing ATPase domains from the proteins in Helicobater pylori. (B-E) The fusion events detected in Helicobater pylori. (B) The tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase (miaB) in Helicobacter pylori containing two [4Fe-4S]⁺ cluster created through the fusion of two putative radical SAM proteins with each one [4Fe-4S]⁺ cluster from Schistosoma mansoni. (C) The Phosphoglycerate kinase in Helicobater pylori created through the fusion of two Phosphoglycerate kinase from Schistosoma mansoni. (D) A threonyl-tRNA synthetase in Helicobater pylori created through the fusion of the C-terminal 3/4 part of a threonyl-tRNA synthetase, including the threonyl-tRNA synthetase-domain are fused with an uncharacterized protein that carries an anticodon-binding domain from Schistosoma mansoni. (E) An Aspartate-tRNA(Asp/Asn) ligase in Helicobacter pylori that it is able to aspartylate aspertat-tRNA and asparagine-tRNA created through the fusion of two threonyl-tRNA synthetase, one with a putative asparagine-tRNA ligase activity and one with a putative aspartate-tRNA ligase activity.