Comparative analysis of the protein sequences encoded in the four euryarchaealspecies whose genomes have been sequenced completely (Methanococcus jannaschii,Methanobacterium thermoautotrophicum, Archaeoglobus fulgidus, and Pyrococcushorikoshii) revealed 1326 orthologous sets, of which 543 are represented in allfour species. The proteins that belong to these conserved euryarchaeal familiescomprise 31%-35% of the gene complement and may be considered the evolutionarily stable core of the archaeal genomes. The core gene set includes the greatmajority of genes coding for proteins involved in genome replication andexpression, but only a relatively small subset of metabolic functions. For manygene families that are conserved in all euryarchaea, previously undetectedorthologs in bacteria and eukaryotes were identified. A number of euryarchaealsynapomorphies (unique shared characters) were identified; these are proteinfamilies that possess sequence signatures or domain architectures that areconserved in all euryarchaea but are not found in bacteria or eukaryotes. Inaddition, euryarchaea-specific expansions of several protein and domain families were detected. In terms of their apparent phylogenetic affinities, the archaealprotein families split into bacterial and eukaryotic families. The majority ofthe proteins that have only eukaryotic orthologs or show the greatest similarity to their eukaryotic counterparts belong to the core set. The families ofeuryarchaeal genes that are conserved in only two or three species constitute arelatively mobile component of the genomes whose evolution should have involvedmultiple events of lineage-specific gene loss and horizontal gene transfer.Frequently these proteins have detectable orthologs only in bacteria or show the greatest similarity to the bacterial homologs, which might suggest a significant role of horizontal gene transfer from bacteria in the evolution of theeuryarchaeota.