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

Author

Listed:
  • Julian Petersen

    (University Leipzig Medical Center)

  • Lukas Englmaier

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

  • Artem V. Artemov

    (Medical University Vienna)

  • Irina Poverennaya

    (Medical University Vienna)

  • Ruba Mahmoud

    (University Leipzig Medical Center)

  • Thibault Bouderlique

    (Medical University Vienna)

  • Marketa Tesarova

    (Brno University of Technology)

  • Ruslan Deviatiiarov

    (Kazan Federal University
    Endocrinology Research Center)

  • Anett Szilvásy-Szabó

    (Institute of Experimental Medicine)

  • Evgeny E. Akkuratov

    (Science for Life Laboratory, 171 65
    University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine)

  • David Pajuelo Reguera

    (Czech Centre for Phenogenomics)

  • Hugo Zeberg

    (Karolinska Institutet
    Karolinska Institutet)

  • Marketa Kaucka

    (Max Planck Institute for Evolutionary Biology)

  • Maria Eleni Kastriti

    (Medical University Vienna
    Karolinska Institutet)

  • Jan Krivanek

    (Masaryk University)

  • Tomasz Radaszkiewicz

    (Masaryk University)

  • Kristína Gömöryová

    (Masaryk University)

  • Sarah Knauth

    (University Leipzig Medical Center)

  • David Potesil

    (Masaryk University)

  • Zbynek Zdrahal

    (Masaryk University)

  • Ranjani Sri Ganji

    (Masaryk University)

  • Anna Grabowski

    (Medical University Vienna)

  • Miriam E. Buhl

    (RWTH Aachen University Hospital)

  • Tomas Zikmund

    (Brno University of Technology)

  • Michaela Kavkova

    (Brno University of Technology
    Masaryk University)

  • Håkan Axelson

    (Lund University, Medicon Village)

  • David Lindgren

    (Lund University, Medicon Village)

  • Rafael Kramann

    (RWTH Aachen University)

  • Christoph Kuppe

    (RWTH Aachen University)

  • Ferenc Erdélyi

    (Institute of Experimental Medicine)

  • Zoltán Máté

    (Institute of Experimental Medicine)

  • Gábor Szabó

    (Institute of Experimental Medicine)

  • Till Koehne

    (University Leipzig Medical Center)

  • Tibor Harkany

    (Medical University Vienna)

  • Kaj Fried

    (Karolinska Institutet)

  • Jozef Kaiser

    (Brno University of Technology)

  • Peter Boor

    (RWTH Aachen University Hospital)

  • Csaba Fekete

    (Institute of Experimental Medicine)

  • Jan Rozman

    (Czech Centre for Phenogenomics
    University of Luxembourg)

  • Petr Kasparek

    (Czech Centre for Phenogenomics)

  • Jan Prochazka

    (Czech Centre for Phenogenomics)

  • Radislav Sedlacek

    (Czech Centre for Phenogenomics)

  • Vitezslav Bryja

    (Masaryk University)

  • Oleg Gusev

    (Kazan Federal University
    Juntendo University)

  • Igor Adameyko

    (Medical University Vienna
    Karolinska Institutet)

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.

Suggested Citation

  • Julian Petersen & Lukas Englmaier & Artem V. Artemov & Irina Poverennaya & Ruba Mahmoud & Thibault Bouderlique & Marketa Tesarova & Ruslan Deviatiiarov & Anett Szilvásy-Szabó & Evgeny E. Akkuratov & D, 2023. "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, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38663-7
    DOI: 10.1038/s41467-023-38663-7
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