Department of Genetics, Stanford University, Stanford, CA, USA.
Department of Genetics, Stanford University, Stanford, CA, USA.
Cell. 2024 Jun 20;187(13):3338-3356.e30. doi: 10.1016/j.cell.2024.04.048. Epub 2024 May 28.
Suspended animation states allow organisms to survive extreme environments. The African turquoise killifish has evolved diapause as a form of suspended development to survive a complete drought. However, the mechanisms underlying the evolution of extreme survival states are unknown. To understand diapause evolution, we performed integrative multi-omics (gene expression, chromatin accessibility, and lipidomics) in the embryos of multiple killifish species. We find that diapause evolved by a recent remodeling of regulatory elements at very ancient gene duplicates (paralogs) present in all vertebrates. CRISPR-Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs as critical for the diapause gene expression program, including genes involved in lipid metabolism. Indeed, diapause shows a distinct lipid profile, with an increase in triglycerides with very-long-chain fatty acids. Our work suggests a mechanism for the evolution of complex adaptations and offers strategies to promote long-term survival by activating suspended animation programs in other species.
暂停生命状态使生物能够在极端环境中存活。非洲蓝珍珠鱼已经进化出滞育期作为一种暂停发育的形式，以在完全干旱中存活下来。然而，极端生存状态进化的机制尚不清楚。为了了解滞育期的进化，我们对多个珍珠鱼物种的胚胎进行了综合多组学（基因表达、染色质可及性和脂质组学）研究。我们发现，滞育期是通过对所有脊椎动物中存在的非常古老的基因重复（旁系同源物）的调控元件进行近期重塑而进化而来的。基于 CRISPR-Cas9 的干扰鉴定了转录因子 REST/NRSF 和 FOXOs 对滞育基因表达程序的关键作用，包括涉及脂质代谢的基因。事实上，滞育期表现出独特的脂质谱，甘油三酯和极长链脂肪酸增加。我们的工作为复杂适应的进化提供了一种机制，并提供了通过在其他物种中激活暂停生命程序来促进长期生存的策略。
