ABSTRACT The rapid growth of genome sequencing has outpaced the development of efficient annotation tools, especially for species lacking transcriptome data. To address this challenge, we present QuickProt, a fast, accurate and user‐friendly homology‐based protein annotation tool. QuickProt constructs a non‐redundant gene model by aligning homologous proteins from closely related species, offering an accurate and cost‐effective solution suitable for large‐scale comparative genomic studies. Benchmarking against BRAKER2 and GALBA across reference genomes demonstrated that QuickProt offers high specificity and dramatically improved runtime, while maintaining competitive annotation accuracy. To demonstrate its utility, we applied QuickProt to diverse genomes, including a non‐model teleost ( Epinephelus bruneus ), two tetraploid Xenopus species and 11 Rutaceae plants. Across these datasets, QuickProt supported robust phylogenetic reconstruction, identification of conserved orthologs and detection of biologically functional genes, pathways, and chromosomal evolution mechanisms, regardless of genome ploidy. Notably, it revealed a potential horizontal gene transfer event between groupers and Vibrio , and uncovered conserved modules involved in volatile oil biosynthesis and oil gland development in citrus. With its scalability and minimal computational demands, QuickProt provides a powerful platform for genome annotation and evolutionary inference. As the number of sequenced genomes continues to expand, QuickProt is a useful tool for accelerating comparative genomics and functional exploration across the tree of life.
Chen et al. (2026) studied this question.