Metabolic Reconfiguration in C. elegans Suggests a Pathway for Widespread Sterol Auxotrophy in the Animal Kingdom
| Autor: | Ron Lebedev, Irina Langier Goncalves, Benjamin Trabelcy, Yoram Gerchman, Shamsuzzama, Amir Sapir |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Auxotrophy medicine.medical_treatment Diapause Biology Genome General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Dafachronic acid Caenorhabditis elegans chemistry.chemical_classification Cholesterol Cholestenes fungi Sterol Steroid hormone Sterols 030104 developmental biology Enzyme chemistry Biochemistry Larva lipids (amino acids peptides and proteins) Animal Nutritional Physiological Phenomena General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Current biology : CB. 30(15) |
| ISSN: | 1879-0445 |
| Popis: | Summary Cholesterol is one of the hallmarks of animals. In vertebrates, the cholesterol synthesis pathway (CSP) is the primary source of cholesterol that has numerous structural and regulative roles [ 1 ]. Nevertheless, the few invertebrates tested for cholesterol synthesis show complete sterol auxotrophy [ 2 , 3 , 4 , 5 , 6 ], raising questions about how animals thrive without cholesterol synthesis and about the prevalence of sterol auxotrophy in animals. In the nematode Caenorhabditis elegans (C. elegans), sterols are the precursors of the steroid hormone dafachronic acid that coordinates development to adulthood [ 7 , 8 ]; thus, sterol-deprived C. elegans arrest at the diapause “dauer” larval stage [ 9 ]. Using this system, we have identified a pathway that converts plant and fungal sterols into cholesterol through the activity of enzymes with sequence similarity to specific human CSP enzymes. Based on this finding, we propose that two critical steps shaped the evolution of animal sterol auxotrophy: (1) the loss of the orthologs of the first three enzymes of the CSP and (2) the co-opting of other downstream enzymes of the CSP for the utilization of dietary sterols. Using this mechanistic signature, we studied the evolution of cholesterol auxotrophy across the animal kingdom. Complete sets of CSP enzymes in basal animals suggest that the loss of cholesterol synthesis occurred during animal evolution. A sterol auxothropy signature in the genomes of many invertebrates, including nematodes and most arthropods, suggests widespread cholesterol auxotrophy in animals. Thus, we propose that this co-opted pathway supports widespread cholesterol auxotrophy by interkingdom interactions between cholesterol-auxotrophic animals and sterol-producing fungi and plants. |
| Databáze: | OpenAIRE |
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