The origin of eukaryotic organisms is one of the most important questions in biology. So far, it has been suggested that eukaryotes are phylogenetically related to Archaea. Indeed, recent progress in archaeal genomic biology seems to have accurately determined the exact position of Archaea in the birth of the Eukaryota. In particular, identifying groups of archaeal species, such as the superphylum TACK and the Asgard archaea, has shown that primitive genes for eukaryotic signature proteins (ESP) already existed in the genomes of these archaeal species. Some ESPs are especially important, including actin and tubulin in the cytoskeleton and the ESCRT complex, which is involved in nuclear membrane formation. There have been many reports that eukaryotic intracellular organelles, such as mitochondria and chloroplasts, evolved from specific symbiotic bacteria. Moreover, eukaryotic genes are disrupted by intronic sequences, which must be removed or “spliced” and the exons connected after the primary transcript is generated, to make a mature functional mRNA. Recently, it has been suggested that the self-splicing factor in both bacterial and archaeal genomes, called “group II intron”, may cause gene disruption. In this review, the frontiers of genome biology are summarized in terms of the importance of prokaryotes (both Archaea and Bacteria) for the origin of Eukarya. From an Earth history perspective, how the increase in atmospheric oxygen concentration at 2.4-2.0 billion years ago may have contributed to the rise of the eukaryotes is discussed.