近日，Christopher Gregg及其研究团队揭示了冬眠哺乳动物的基因组趋同阐明了下丘脑代谢调节的遗传学。2025年7月31日，国际知名学术期刊《科学》发表了这一成果。

研究团队以冬眠谱系中的趋同进化变化为主题来定义保守的顺式调控元件（CREs）和代谢程序。研究人员对喂食、禁食和冷冻状态下的无主题下丘脑基因表达和染色质动力学进行了表征，然后对冬眠谱系和非冬眠谱系进行了主题比较基因组学研究，以确定在冬眠动物中具有趋同变化的顺式元件。多组学方法确定了CREs、枢纽基因、调控程序和潜在谱系分化的细胞类型。冬眠者对调节下丘脑反应的CREs积累了功能丧失效应，禁食后的再进食期是具有趋同进化变化的分子过程的关键阶段。这项工作为利用冬眠动物的适应性来理解人类代谢控制提供了一个遗传框架。

研究人员表示，极端的代谢适应可以阐明控制哺乳动物代谢的遗传程序。

附：英文原文

Title: Genomic convergence in hibernating mammals elucidates the genetics of metabolic regulation in the hypothalamus

Author: Elliott Ferris, Josue D. Gonzalez Murcia, Adriana Cristina Rodriguez, Susan Steinwand, Cornelia Stacher Hrndli, Dimitri Traenkner, Pablo J. Maldonado-Catala, Christopher Gregg

Issue&Volume: 2025-07-31

Abstract: Extreme metabolic adaptations can elucidate genetic programs that govern mammalian metabolism. Here, we used convergent evolutionary changes in hibernating lineages to define conserved cis-regulatory elements (CREs) and metabolic programs. We characterized mouse hypothalamus gene expression and chromatin dynamics across fed, fasted, and refed states and then used comparative genomics of hibernating versus nonhibernating lineages to identify cis elements with convergent changes in hibernators. Multi-omics approaches pinpointed CREs, hub genes, regulatory programs, and cell types underlying lineage divergence. Hibernators accumulated loss-of-function effects for CREs regulating hypothalamic responses, and the refeeding period after fasting served as a key phase for molecular processes with convergent evolutionary changes. This work provides a genetic framework for harnessing hibernator adaptations to understand human metabolic control.

DOI: adp4025

Source: https://www.science.org/doi/10.1126/science.adp4025