Journal
EMBO REPORTS
Volume 12, Issue 1, Pages 63-70Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2010.170
Keywords
evolution; HIF; hypoxia; oxygen sensing; Trichoplax
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Funding
- Biotechnology and Biological Sciences Research Council
- Wellcome Trust
- German Science Foundation
- Rhodes Scholarship
- William R. Miller Junior Research Fellowship
- BBSRC [BB/J003018/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J003018/1] Funding Source: researchfish
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The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom.
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