Fig. 4. Three methods of assigning orthology relationships. Species are designated by letters and paralogs by numbers. (A) KOG. The NCBI KOG detects reciprocally best-matching proteins from BLAST searches as orthologs. An ortholog group is thus defined as the union of best BLAST hits among all pairwise comparisons of multiple species. In the example shown, species A and species B each have a 1:1 ortholog, but species C has two orthologous proteins. (B) InParanoid. Since inter-genome reciprocal best BLAST analysis forces a one-to-one relationship, InParanoid also detects intra-genome best BLAST hits as co-orthologs. Solid arrows, inter-genome BLAST; dashed arrows, intra-genome BLAST. (C) TreeFam. In this approach, the relationships among proteins are defined by phylogenetic analysis.