The phylogenetic distribution of Methanococcus jannaschii proteins can provide, for the first time, an estimate of the genome content of the last common ancestor of the three domains of life. Relying on annotation and comparison with reference to the species distribution of sequence similarities results in 324 proteins forming the universal family set. This set is very well characterized and relatively small and nonredundant, containing 301 biochemical functions, of which 246 are unique. This universal function set contains mostly genes coding for energy metabolism or information processing. It appears that the Last Universal Common Ancestor was an organism with metabolic networks and genetic machinery similar to those of extant unicellular organisms.