Evolution of the TOR Pathway

• Published in: Journal of molecular evolution Vol. 73; no. 3-4; pp. 209 - 220
• Main Authors: van Dam, Teunis J. P., Zwartkruis, Fried J. T., Bos, Johannes L., Snel, Berend
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.10.2011; Springer Nature B.V; Springer Nature
• Subjects: AGC kinases; Amino Acid Sequence; Animal Genetics and Genomics; Animals; BASIC BIOLOGICAL SCIENCES; Biomedical and Life Sciences; Cancer; Cell Biology; Conserved Sequence; Eukaryotes; Evolution, Molecular; Evolutionary Biology; Fungal Proteins - chemistry; Fungal Proteins - genetics; Gene Duplication; Gene Expression Regulation; Gene Regulatory Networks; Genetics; Humans; Kinases; Life Sciences; Metabolic disorders; Microbiology; Models, Genetic; Molecular biology; molecular evolution; Multiprotein Complexes - genetics; Pathway evolution; Phylogeny; Plant Genetics and Genomics; Plant Sciences; protein-serine kinase; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Rheb; Sequence Homology, Amino Acid; Signal transduction; Signal Transduction - genetics; TOR; TOR Serine-Threonine Kinases - chemistry; TOR Serine-Threonine Kinases - genetics; Transcription Factors - chemistry; Transcription Factors - genetics; TSC1-2 complex; Yeasts; Pathway evolution; TSC1-2 complex; AGC kinases; Rheb; TOR
• ISSN: 0022-2844; 1432-1432
• DOI: 10.1007/s00239-011-9469-9

The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub-functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes.