A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology

0575265 - ÚMG 2024 RIV US eng J - Článek v odborném periodiku
Petersen, J. - Englmaier, L. - Artemov, A.V. - Poverennaya, I. - Mahmoud, R. - Bouderlique, T. - Tesařová, M. - Deviatiiarov, R. - Szilvasy-Szabo, A. - Akkuratov, E. E. - Pajuelo Reguera, David - Zeberg, H. - Kaucka, M. - Kastriti, M.E. - Krivanek, J. - Radaszkiewicz, T. - Goemoeryova, K. - Knauth, S. - Potěšil, D. - Zdráhal, Z. - Ganji, R.S. - Grabowski, A. - Buhl, M. E. - Zikmund, T. - Kavková, M. - Axelson, H. - Lindgren, D. - Kramann, R. - Kuppe, C. - Erdelyi, F. - Mate, Z. - Szabó, G. - Koehne, T. - Harkany, T. - Fried, K. - Kaiser, J. - Boor, P. - Fekete, C. - Rozman, Jan - Kašpárek, Petr - Procházka, Jan - Sedláček, Radislav - Bryja, V. … celkem 45 autorů
A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.
Nature Communications. Roč. 14, č. 1 (2023), č. článku 3092. E-ISSN 2041-1723
Grant CEP: GA MŠMT(CZ) LM2018126
Výzkumná infrastruktura: e-INFRA CZ - 90140
Institucionální podpora: RVO:68378050
Klíčová slova: COVERAGE NEANDERTHAL GENOME * TOCA-1 * evolutionary divergence * FAME
Obor OECD: Cell biology
Impakt faktor: 16.6, rok: 2022
Způsob publikování: Open access
https://www.nature.com/articles/s41467-023-38663-7

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.
Trvalý link: https://hdl.handle.net/11104/0346243