Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.
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2010-09-23
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BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki. RESULTS: Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions. CONCLUSIONS: The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural environments.
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Shertz, Cecelia A, Robert J Bastidas, Wenjun Li, Joseph Heitman and Maria E Cardenas (2010). Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom. BMC Genomics, 11. p. 510. 10.1186/1471-2164-11-510 Retrieved from https://hdl.handle.net/10161/4347.
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Robert J Bastidas
Robert Bastidas is an Assistant Research Professor in the Department of Integrative Immunobiology at Duke University, where his primary research focuses on host-pathogen interactions. Dr. Bastidas employs Chlamydia trachomatis as a model system for understanding the mechanisms enabling intracellular bacterial pathogens to thrive within human cells. In addition, his recent interests extend to investigating how infections by bacterial pathogens contribute to the shaping of human immune responses. Dr. Bastidas also holds the position of Associate Editor for Frontiers in Cellular and Infection Microbiology.
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