title: Evolution of the TSC1/TSC2-TOR signaling pathway.
abstract: The TSC1/TSC2-TOR signaling pathway [the signaling pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)-TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were "bolted on" in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic "tree of life" lies between the unikonts and other organisms, should therefore be reevaluated.
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Jaco
authors.initials: J
authors.lastname: Serfontein
authors.forename: R Ellen R
authors.initials: RE
authors.lastname: Nisbet
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Howe
authors.forename: Petrus J
authors.initials: PJ
authors.lastname: de Vries
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C515347:TSC1 protein, Drosophila; C117726:gig protein, Drosophila; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases