The traditional tree of life shows eukaryotes as a distinct lineage of living things, but many studies have suggested that the first eukaryotic cells were chimeric, descended from both Eubacteria (through the mitochondrion) and Archaebacteria. Eukaryote nuclei thus contain genes of both eubacterial and archaebacterial origins, and these genes have different functions within eukaryotic cells. Here we report that archaebacterium-derived genes are significantly more likely to be essential to yeast viability, are more highly expressed, and are significantly more highly connected and more central in the yeast protein interaction network. These findings hold irrespective of whether the genes have an informational or operational function, so that many features of eukaryotic genes with prokaryotic homologs can be explained by their origin, rather than their function. Taken together, our results show that genes of archaebacterial origin are in some senses more important to yeast metabolism than genes of eubacterial origin. This importance reflects these genes' origin as the ancestral nuclear component of the eukaryotic genome.endosymbiosis | gene essentiality | eukaryote origin | protein interaction network A s one of the three domains of cellular life, the eukaryotes are typically described as the sister group to the archaebacteria. This sister group relationship describes the evolutionary history of the "nuclear-cytoplasmic" component of eukaryotes, with mitochondria and plastids being of endosymbiotic bacterial origin (e.g., ref. 1). In this traditional scenario, the unique features of extant eukaryotes were gradually acquired in the eukaryote stem group before the endosymbiotic acquisition of the mitochondrion. Thus, the acquisition of the mitochondrion was an important, but not foundational, step in eukaryote origins, occurring subsequent to the evolution of many characteristic features of eukaryotic cell biology. Early molecular phylogenies of ribosomal RNA genes support this scenario (see refs. 2 and 3 for reviews), as do several other molecular markers. Many nuclear genes are more closely related to eubacterial homologs than to any known archaebacterial sequence (4, 5) and appear to have been transferred to the nucleus from the ancestral mitochondrial genome by a process known as endosymbiotic gene transfer (1, 6). A similar process occurred after other symbiotic events, for example, the introduction of many chloroplast-derived genes into the nuclei of green plants (6).An alternative view of eukaryotic nuclear-cytoplasmic origins, first suggested by Lake (7-9) is that this lineage arose from within, rather than as a sister to, the archaebacteria. This view is supported by molecular phylogenies showing that many eukaryote genes actually derive from within the archaebacterial domain (7-11), including a recent reanalysis of informational genes with modern phylogenetic methods (10). It also has become clear that those eukaryotes that lack mitochondria either are derived from organisms that have mitochondria or themse...