| Autor: |
Steinwand S; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Stacher Hörndli C; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Ferris E; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Emery J; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Gonzalez Murcia JD; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Cristina Rodriguez A; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Leydsman TC; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA., Chaix A; Department of Nutrition and Integrative Physiology, University of Utah; Salt Lake City, 84105, USA., Thomas A; Division of Epidemiology, University of Utah; Salt Lake City, 84105, USA.; Study Design and Biostatistics Center, University of Utah; Salt Lake City, 84105, USA., Davey C; Mutation Generation & Detection Core Facility, University of Utah; Salt Lake City, 84105, USA., Gregg C; Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA.; Department of Human Genetics, University of Utah; Salt Lake City, 84105, USA. |
| Abstrakt: |
Our study elucidates functional roles for conserved cis- elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity ( Fto ) locus. Some hibernation-linked cis- elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis- elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis- element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis- element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control. |
