Localizing proteins in the cell from their phylogenetic profiles

We introduce a computational method for identifying subcellular locations o f proteins from the phylogenetic distribution of the homologs of organellar proteins. This method is based on the observation that proteins localized to a given organelle by experiments tend to share a characteristic phylogen etic distribution of their homologs-a phylogenetic profile. Therefore any o ther protein can be localized by its phylogenetic profile. Application of t his method to mitochondrial proteins reveals that nucleus-encoded proteins previously known to be destined for mitochondria fall into three groups: pr okaryote-derived, eukaryote-derived, and organism-specific (i,e,, found onl y in the organism under study). Prokaryote-derived mitochondrial proteins c an be identified effectively by their phylogenetic profiles. In the yeast S accharomyces cerevisiae, 361 nucleus-encoded mitochondrial proteins can be identified at 50% accuracy with 58% coverage. From these values and the pro portion of conserved mitochondrial genes, it can be inferred that approxima te to 630 genes, or 10% of the nuclear genome, is devoted to mitochondrial function. In the worm Caenorhabditis elegans, we estimate that there are ap proximate to 660 nucleus-encoded mitochondrial genes, or 4% of its genome, with approximate to 400 of these genes contributed from the prokaryotic mit ochondrial ancestor. The large fraction of organism-specific and eukaryote- derived genes suggests that mitochondria perform specialized roles absent f rom prokaryotic mitochondrial ancestors. We observe measurably distinct phy logenetic profiles among proteins from different subcellular compartments, allowing the general use of prokaryotic genomes in learning features of euk aryotic proteins.