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.
Bibliographical noteFunding Information:
We thank D Pe’er, I Nachman and R Nelken for critical reading of this manuscript, and M Ethier, B Matenuto and A Karger for excellent technical support. A.R. holds a Career Award at the Scientific Interface from the the Burroughs Wellcome Fund. N.F. was supported in part by an Israel Science Foundation grant.