Department of Orthodontics, University Leipzig Medical Center, Leipzig, Germany.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.
Nat Commun. 2023 May 29;14(1):3092. doi: 10.1038/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.
在这项研究中，我们利用比较基因组学揭示了一个具有未知功能的基因（1700011H14Rik/C14orf105/CCDC198），我们将其命名为 FAME（与代谢和能量相关的因子）。我们观察到 FAME 在鸟类和哺乳动物中表现出异常高的进化分歧。通过比较单核苷酸多态性，我们发现 FAME 基因从尼安德特人到现代人类的基因流。我们对动物进行了基因敲除实验，观察到 Fame 基因敲除动物的体重改变和能量消耗减少，这与将 FAME 与人类更高的体重指数相关的全基因组关联研究结果一致。基因表达和亚细胞定位分析表明，FAME 是一种富含肾脏的膜结合蛋白。尽管基因敲除导致肾脏结构正常，但我们检测到尿液中白蛋白升高，血液中铁蛋白降低。通过实验验证，我们证实了 FAME 与铁蛋白之间的相互作用，并显示出它们在囊泡和质膜中的共定位。
