Twenty completely sequenced cellular genomes from the three major domains were analyzed using twice one-way BLAST searches in order to define the set of the most conserved protein-encoding sequences to characterize the gene complement of the last common ancestor of extant life. The resulting set is dominated by different putative ATPases, and by molecules involved in gene expression and RNA metabolism. DEAD-type RNA helicase and enolase genes, which are known to be part of the RNA degradosome, are as conserved as many transcription and translation genes. This suggests the early evolution of a control mechanism for gene expression at the RNA level, providing additional support to the hypothesis that during early cellular evolution RNA molecules played a more prominent role. Conserved sequences related to biosynthetic pathways include those encoding putative phosphoribosyl pyrophosphate synthase and thioredoxin, which participate in nucleotide metabolism. Although the information contained in the available databases corresponds only to a minor portion of biological diversity, the sequences reported here are likely to be part of an essential and highly conserved pool of proteins domains common to all organisms.