REvolutionH-tl: A Fast and Robust Tool for Decoding Evolutionary Gene Histories

Ramirez-Rafael, J. A.; Korchmaros, A.; Avina-Padilla, K.; Lopez-Sanchez, A.; Martinez-Medina, G.; Hernandez-Alvarez, A. J.; Hellmuth, M.; Stadler, P. F.; Hernandez-Rosales, M.

doi:10.1101/2025.04.03.646975

bioRxiv · 10.1101/2025.04.03.646975

REvolutionH-tl: A Fast and Robust Tool for Decoding Evolutionary Gene Histories

Ramirez-Rafael, J. A.·Korchmaros, A.·Avina-Padilla, K.·Lopez-Sanchez, A.·Martinez-Medina, G.·Hernandez-Alvarez, A. J.·Hellmuth, M.·Stadler, P. F.·Hernandez-Rosales, M.

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Abstract

REvolutionH-tl is a fast, scalable, and integrated software platform for inferring orthology relationships, gene trees, species trees, and reconciled evolutionary scenarios directly from sequence data. Built upon the formal framework of best match graphs (BMGs), REvolutionH-tl predicts orthogroups and orthologous gene pairs with high accuracy, requiring neither precomputed trees nor multiple external tools. The software reconstructs event-labeled gene and species trees, seamlessly integrating reconciliation to produce fast, accurate, and biologically insightful evolutionary scenarios. Through extensive benchmarking on synthetic datasets with known ground truth, REvolutionH-tl outperforms or matches the accuracy of established tools such as OrthoFinder, Proteinortho, RAxML, GeneRax, and RANGER-DTL, while achieving significantly lower runtimes. A key innovation of REvolutionH-tl is its built-in support for detailed, publication-ready visualizations, which allow users to explore genome evolution dynamics, orthogroup composition, and reconciliation results with clarity and ease. These visual features position REvolutionH-tl as the first platform of its kind to combine analytical precision with intuitive interpretability. The software is open-source, cross-platform, and freely available at https://pypi.org/project/revolutionhtl/, providing a robust solution for large-scale evolutionary analyses in comparative genomics. Author summaryComparative genomics relies on understanding how genes evolve across species. This involves identifying groups of related genes, reconstructing their evolutionary trees, and aligning them with the evolutionary history of species. These steps are typically performed using multiple tools, often requiring manual integration and technical expertise. We present REvolutionH-tl, an open-source software that automates the entire evolutionary reconstruction process--starting from protein sequences and producing gene trees, species trees, orthology assignments, and reconciled evolutionary scenarios. Unlike existing tools, REvolutionH-tl also includes built-in, high-quality visualizations that help users interpret complex evolutionary events such as gene duplications and losses. We evaluated REvolutionH-tl on simulated genomes with known evolutionary histories and found that it matches or exceeds the performance of widely used tools, while being significantly faster. Its visual output makes evolutionary analysis more accessible and interpretable, offering a valuable resource for researchers studying genome evolution.

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Ramirez-Rafael, J. A., Korchmaros, A., Avina-Padilla, K., Lopez-Sanchez, A., Martinez-Medina, G., Hernandez-Alvarez, A. J., Hellmuth, M., Stadler, P. F., Hernandez-Rosales, M.. 2025-04-08. REvolutionH-tl: A Fast and Robust Tool for Decoding Evolutionary Gene Histories. https://doi.org/10.1101/2025.04.03.646975

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