C-G.C.11: FuFisOr Finder: A Bioinformatics Pipeline for Detecting Orthology Based Fusion and Fission Events in Protein Sequences
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Keywords
fusion fission evolution bacteria python ortholog
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The prediction of homologous genes is fundamental for functional annotation transfer, evolutionary analysis, and comparative genomics. Orthology inference tools such as Proteinortho, OrthoFinder, SonicParanoid, and OrthoMCL distinguish orthologs and paralogs but typically overlook gene fusion and fission events, which also play a key role in protein evolution by reshaping domain architectures and enabling functional diversification.
We demonstrate that orthology data can be leveraged to detect fusion and fission events, extending its utility beyond conventional applications. To this end, we developed FuFisOr, a lightweight post-processing pipeline designed to identify such events from orthology inference outputs, using Proteinortho as an example. The pipeline detects candidate fission sets aligning to potential fusion proteins by exploiting reciprocal best hits, avoiding additional similarity searches. FuFisOr integrates seamlessly with Proteinortho, requires minimal pre-processing, and is adaptable to other tools.
FuFisOr was evaluated on three bacterial proteomes: Pseudomonas aeruginosa, Bacillus subtilis, and Escherichia coli, identifying 15 high-confidence fusion/fission events validated using InterPro domain annotations and AlphaFold2 structural models superimposed in UCSF Chimera. One representative case involves the riboflavin biosynthesis protein RibBA in B. subtilis, which contains both DHBP_synthase and GTP_cyclohydro2 domains; in E. coli, these exist separately as RibB and RibA, indicating a fission event.
These results highlight FuFisOr ability to detect biologically meaningful events and extend orthology-based analyses with a scalable, reproducible solution for studying protein evolution.
Co-authors: Paul Klemm, Marcus Lechner
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