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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dc.contributor.authorKaiser, Markétacs
dc.contributor.authorZikmund, Tomášcs
dc.contributor.authorKavková, Michaelacs
dc.contributor.authorKaiser, Jozefcs
dc.coverage.issue3092cs
dc.coverage.volume14cs
dc.date.issued2023-05-29cs
dc.description.abstractIn 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.en
dc.formattextcs
dc.format.extent1-22cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationNATURE COMMUNICATIONS. 2023, vol. 14, issue 3092, p. 1-22.en
dc.identifier.doi10.1038/s41467-023-38663-7cs
dc.identifier.issn2041-1723cs
dc.identifier.orcid0000-0002-5200-7365cs
dc.identifier.orcid0000-0003-2948-5198cs
dc.identifier.orcid0000-0001-7435-9292cs
dc.identifier.orcid0000-0002-7397-125Xcs
dc.identifier.other185232cs
dc.identifier.researcheridV-3696-2018cs
dc.identifier.researcheridG-9491-2014cs
dc.identifier.researcheridD-6800-2012cs
dc.identifier.scopus7402184758cs
dc.identifier.urihttp://hdl.handle.net/11012/214444
dc.language.isoencs
dc.publisherNATURE PORTFOLIOcs
dc.relation.ispartofNATURE COMMUNICATIONScs
dc.relation.urihttps://www.nature.com/articles/s41467-023-38663-7cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2041-1723/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectFAMEen
dc.subjectEvolutionary geneticsen
dc.subjectGenetic modelsen
dc.subjectKidneyen
dc.titleA previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiologyen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-185232en
sync.item.dbtypeVAVen
sync.item.insts2024.03.01 18:46:20en
sync.item.modts2024.03.01 18:14:21en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Pokročilé instrumentace a metody pro charakterizace materiálůcs
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Pokročilé instrumentace a metody pro charakterizace materiálů