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The KEGG Orthology (KO) system has been used as a basic framework of the KEGG database for linking genes in the genome to pathways and other molecular networks. KOs are manually defined orthologs representing conserved genes with relevance to molecular and higher-level functions. Here, the KO system is used to define genomic features, including the gene content by the composition of KOs and the gene order on the chromosome by the sequence of KOs, and to compare organisms, organism groups and viruses according to the similarity of KO compositions and KO sequences. The compositions of KEGG modules, manually defined functional sets of KOs, and VOGs, computationally derived ortholog groups for viruses, are also used as genomic features. The similarity analysis of organism groups by KO compositions has revealed a close relationship of Bacteria and Archaea, which differs from the three domains of life in evolution, but which is likely to reflect similarity of metabolic and other cellular functions represented by KOs. A collection of tools is named KEGG Syntax (https://www.kegg.jp/kegg/syntax/) and can be used to analyze the user's data as well as the genomes already registered in KEGG.
Kanehisa et al. (Thu,) studied this question.