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

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Authors

PETERSEN Julian ENGLMAIER Lukas ARTEMOV Artem V POVERENNAYA Irina MAHMOUD Ruba BOUDERLIQUE Thibault TESAROVA Marketa DEVIATIIAROV Ruslan SZILVASY-SZABO Anett AKKURATOV Evgeny E DAVID Pajuelo Reguera ZEBERG Hugo KAUCKA Marketa KASTRITI Maria Eleni KŘIVÁNEK Jan RADASZKIEWICZ Tomasz Witold GÖMÖRYOVÁ Kristína KNAUTH Sarah POTĚŠIL David ZDRÁHAL Zbyněk GANJI Sri Ranjani GRABOWSKI Anna BUHL Miriam E ZIKMUND Tomas KAVKOVÁ Michaela AXELSON Hakan LINDGREN David KRAMANN Rafael KUPPE Christoph ERDELYI Ferenc MATE Zoltan SZABO Gabor KOEHNE Till HARKANY Tibor FRIED Kaj KAISER Jozef BOOR Peter FEKETE Csaba ROZMAN Jan KASPAREK Petr PROCHAZKA Jan SEDLACEK Radislav BRYJA Vítězslav GUSEV Oleg ADAMEYKO Igor

Year of publication 2023
Type Article in Periodical
Magazine / Source Nature Communications
MU Faculty or unit

Faculty of Science

Citation
Web https://www.nature.com/articles/s41467-023-38663-7
Doi http://dx.doi.org/10.1038/s41467-023-38663-7
Keywords Evolutionary genetics; Genetic models; Kidney; Protein
Description 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.
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