The COG database, which includes clusters of orthologous groups (COGs) of proteins from prokaryotes and unicellular eukaryotes, has been updated to include eukaryotic orthologous groups (KOGs). The COG system, based on orthologous relationships between genes, is a useful framework for comparative genomics and functional annotation of genomes. The updated COG collection consists of 138,458 proteins forming 4,873 COGs, covering 75% of the proteins in 66 unicellular genomes. The KOGs, constructed from 7 eukaryotic genomes, include 59,838 proteins, or about 54% of the analyzed eukaryotic gene products. The KOGs reveal a conserved core of ~20% of the set, reflecting the evolutionary stability of eukaryotic genomes. The COG and KOG systems are valuable resources for functional annotation and evolutionary studies of newly sequenced genomes, including complex eukaryotes.The COG database, which includes clusters of orthologous groups (COGs) of proteins from prokaryotes and unicellular eukaryotes, has been updated to include eukaryotic orthologous groups (KOGs). The COG system, based on orthologous relationships between genes, is a useful framework for comparative genomics and functional annotation of genomes. The updated COG collection consists of 138,458 proteins forming 4,873 COGs, covering 75% of the proteins in 66 unicellular genomes. The KOGs, constructed from 7 eukaryotic genomes, include 59,838 proteins, or about 54% of the analyzed eukaryotic gene products. The KOGs reveal a conserved core of ~20% of the set, reflecting the evolutionary stability of eukaryotic genomes. The COG and KOG systems are valuable resources for functional annotation and evolutionary studies of newly sequenced genomes, including complex eukaryotes.