The PHRINGE Project

Soon there will be complete genome sequences for hundreds of eukaryotes and thousands of prokaryotes from across the Tree of Life (see a list at Genomes Online). It is imperative that we quickly develop better and faster methods for interpreting these data.

PHRINGE ("Phylogenetic Resources for the Interpretation of Genomes") reconstructs the evolutionary history of all gene families, sorting out their patterns of orthologous (related by lineage splitting) and paralogous (related by gene duplication) relationships. Not only is this important for understanding the pattern and processes of genome evolution, but this phylogenetic framework is the best tool for accurate inference of gene function. This is in contrast with non-phylogenetic methods in common usage that rely on simple similarity matching and that are known to make errors, including the incorrect association of the pairs of more slowly evolving paralogs and lack of annotation for those more rapidly evolving.

Why is it important to sort orthologs and paralogs by evolutionary analysis?

Summary of the method: 

PHRINGE includes the complete gene sets of many completely sequenced genomes, uses a graph-based method to cluster genes into families by a novel protocol that respects the evolutionary relationships among the organisms, and constructs an evolutionary tree of each cluster. Clusters are built at each node of the tree of the organisms, so that the user can choose the most comprehensive set of gene relationships, or can look at just a taxonomically restricted analysis, with typically greater accuracy. It presents the multiple sequence alignments, a comparison of the exon-intron structures of each member of each cluster, links to functional genomics databases, and an evolutionary tree of each gene family. Automated scripts reconstruct patterns of duplications and gene losses. The associated Synteny Viewer allows the user to see the relative physical locations of sets of orthologs in sets of user-specified genomes.

See details of the PHRINGE pipeline here

Projects using these methods:

An earlier version on which these tools were built (called "PhIGs"), was used to demonstrate that two rounds of whole genome duplication occurred at the base of the vertebrates.  Access the full text of the publication or read the journal's news article.

These methods also constituted a major part of the analysis of the genomes of the oomycetes Phytophthora sojae and Phytophthora ramorum, the crustacean Daphnia pulex, and the frog Xenopus tropicalis.