Nature Communications (May 2023)
A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology
- Julian Petersen,
- Lukas Englmaier,
- Artem V. Artemov,
- Irina Poverennaya,
- Ruba Mahmoud,
- Thibault Bouderlique,
- Marketa Tesarova,
- Ruslan Deviatiiarov,
- Anett Szilvásy-Szabó,
- Evgeny E. Akkuratov,
- David Pajuelo Reguera,
- Hugo Zeberg,
- Marketa Kaucka,
- Maria Eleni Kastriti,
- Jan Krivanek,
- Tomasz Radaszkiewicz,
- Kristína Gömöryová,
- Sarah Knauth,
- David Potesil,
- Zbynek Zdrahal,
- Ranjani Sri Ganji,
- Anna Grabowski,
- Miriam E. Buhl,
- Tomas Zikmund,
- Michaela Kavkova,
- Håkan Axelson,
- David Lindgren,
- Rafael Kramann,
- Christoph Kuppe,
- Ferenc Erdélyi,
- Zoltán Máté,
- Gábor Szabó,
- Till Koehne,
- Tibor Harkany,
- Kaj Fried,
- Jozef Kaiser,
- Peter Boor,
- Csaba Fekete,
- Jan Rozman,
- Petr Kasparek,
- Jan Prochazka,
- Radislav Sedlacek,
- Vitezslav Bryja,
- Oleg Gusev,
- Igor Adameyko
Affiliations
- Julian Petersen
- Department of Orthodontics, University Leipzig Medical Center
- Lukas Englmaier
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Artem V. Artemov
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- Irina Poverennaya
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- Ruba Mahmoud
- Department of Orthodontics, University Leipzig Medical Center
- Thibault Bouderlique
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- Marketa Tesarova
- Central European Institute of Technology, Brno University of Technology
- Ruslan Deviatiiarov
- Regulatory Genomics Research Center, Institute of Fundamental Medicine and Biology, Kazan Federal University
- Anett Szilvásy-Szabó
- Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine
- Evgeny E. Akkuratov
- Department of Applied Physics, Royal Institute of Technology, Science for Life Laboratory, 171 65
- David Pajuelo Reguera
- Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics
- Hugo Zeberg
- Department of Neuroscience, Karolinska Institutet
- Marketa Kaucka
- Max Planck Institute for Evolutionary Biology
- Maria Eleni Kastriti
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- Jan Krivanek
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University
- Tomasz Radaszkiewicz
- Institute of Experimental Biology, Faculty of Science, Masaryk University
- Kristína Gömöryová
- Institute of Experimental Biology, Faculty of Science, Masaryk University
- Sarah Knauth
- Department of Orthodontics, University Leipzig Medical Center
- David Potesil
- Central European Institute of Technology, Masaryk University
- Zbynek Zdrahal
- Central European Institute of Technology, Masaryk University
- Ranjani Sri Ganji
- Central European Institute of Technology, Masaryk University
- Anna Grabowski
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- Miriam E. Buhl
- Institute of Pathology & Electron Microscopy Facility, RWTH Aachen University Hospital
- Tomas Zikmund
- Central European Institute of Technology, Brno University of Technology
- Michaela Kavkova
- Central European Institute of Technology, Brno University of Technology
- Håkan Axelson
- Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village
- David Lindgren
- Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village
- Rafael Kramann
- Institute of Experimental Medicine and Systems Biology, RWTH Aachen University
- Christoph Kuppe
- Institute of Experimental Medicine and Systems Biology, RWTH Aachen University
- Ferenc Erdélyi
- Medical Gene Technology Unit, Institute of Experimental Medicine
- Zoltán Máté
- Medical Gene Technology Unit, Institute of Experimental Medicine
- Gábor Szabó
- Medical Gene Technology Unit, Institute of Experimental Medicine
- Till Koehne
- Department of Orthodontics, University Leipzig Medical Center
- Tibor Harkany
- Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna
- Kaj Fried
- Department of Physiology and Pharmacology, Karolinska Institutet
- Jozef Kaiser
- Central European Institute of Technology, Brno University of Technology
- Peter Boor
- Institute of Pathology & Electron Microscopy Facility, RWTH Aachen University Hospital
- Csaba Fekete
- Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine
- Jan Rozman
- Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics
- Petr Kasparek
- Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics
- Jan Prochazka
- Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics
- Radislav Sedlacek
- Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics
- Vitezslav Bryja
- Institute of Experimental Biology, Faculty of Science, Masaryk University
- Oleg Gusev
- Regulatory Genomics Research Center, Institute of Fundamental Medicine and Biology, Kazan Federal University
- Igor Adameyko
- Department of Neuroimmunology, Center for Brain Research, Medical University Vienna
- DOI
- https://doi.org/10.1038/s41467-023-38663-7
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 22
Abstract
Abstract In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.
