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UNLABELLED: Gene duplication and divergence is a major evolutionary force. Despite the growing number of fully sequenced genomes, methods for investigating these events on a genome-wide scale are still in their infancy. Here, we present SYNERGY, a novel and scalable algorithm that uses sequence similarity and a given species phylogeny to reconstruct the underlying evolutionary history of all genes in a large group of species. In doing so, SYNERGY resolves homology relations and accurately distinguishes orthologs from paralogs. We applied our approach to a set of nine fully sequenced fungal genomes spanning 150 million years, generating a genome-wide catalog of orthologous groups and corresponding gene trees. Our results are highly accurate when compared to a manually curated gold standard, and are robust to the quality of input according to a novel jackknife confidence scoring. The reconstructed gene trees provide a comprehensive view of gene evolution on a genomic scale. Our approach can be applied to any set of sequenced eukaryotic species with a known phylogeny, and opens the way to systematic studies of the evolution of individual genes, molecular systems and whole genomes.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.