Final Activity Report Summary - UNIVERSAL LIFE (Inferring the Universal Tree, or Network, of Life: Genomics, Supertrees, and Supernetworks) The objectives of this project were both methodological and applied. The methodological objectives consisted in developing new computational tools to be used in genomics and, more generally, to study biological evolution. Our applied objectives were to resolve some long-standing issues related to the origins and early evolution of cellular life. Our main goals were all positively accomplished and included: 1. the collection of strong genomic evidence supporting the thermophilic (i.e. at high temperature) origin of cellular life; and 2. the demonstration that the 'tree of life', the tree-like diagram representing the descent of all living organisms from a single common ancestor, was inadequate to represent the real complexity of life evolutionary history. More than 20 alternative hypotheses attempting to explain the evolutionary origins of eukaryotes, the group to which animals and plants belong, were proposed during the last 100 years. Using one of the new computational tools we developed, namely a 'supertree-based phylogenetic-signal stripping' method, we painstakingly performed the first exhaustive, empirical investigation of the signals embedded in every publicly available, complete eukaryotic genome, and compared these signals with those of 169 prokaryotic genomes, including both archaebacteria and eubacteria. The results of the analysis rejected all but two of the hypotheses that were proposed to explain the origin of eukaryotes. The only two hypotheses that were consistent with our results were unsurprisingly very similar, both conjecturing that eukaryotes were not an independently evolved lineage. They were rather a genomic chimera that originated from the genomic fusion of an alpha-proteobacterum (the ancestor of the mitochondrion) and an archaebacterium (the host cell). The significance of this result was that, contrary to what was generally believed, the free-living ancestor of the mitochondrion had a role in the evolutionary history of the eukaryotes as important, and perhaps even more important, than that of the archaebacterial ancestor of the host cell. A consequence of our result, which was consistent with the current evidence, was that primitively amitochondriate eukaryotes never existed. Furthermore, we obtained the first genomic evidence pinpointing that the archaebacterial group was most closely related to the eukaryotes (the thermoplasmatales). When we started this study, it was still unclear whether life evolved in a tree-like fashion, or whether the relationships among all living organisms were network-like. The results of our study settled this question. Eukaryotes were chimera and the evolutionary relationships of life should be represented using a hybridisation network, not a tree.