The complete 1.66 megabase pair genome sequence of the extreme thermophilic, autotrophic archaeon Methanococcus jannaschii has been determined by whole-genome random sequencing. Out of a total of 1751 predicted protein coding genes, only 44% could be assigned a putative cellular role with high confidence, and only 57% are homologous to genes known in other organisms. For 43% of the M. jannaschii genes no related gene is known in any other organism. Although the majority of the genes related to energy production, cell division, and metabolism in M. jannaschii are most similar to those found in Bacteria, most of the genes involved in the processing of information (transcription, translation, and replication) are more similar to their counterparts in Eukaryotes. The analysis of the M. jannaschii genome holds not only clues for the basis of life under extreme conditions, but the comparison of its information content with that of the genomes from other model organisms, like the bacterium Escherichia coli and the eukaryote Saccharomyces cerevisiae, also provides clues for the reconstruction of the history of many gene families and for the history of life on earth.