Abstract: Species that live in extreme environments evolve unique adaptations for survival. Understanding how extreme adaptations evolve can reveal new pathways with important ramifications for survival in all organisms. African killifish have evolved an extremely short lifespan and a form of 'suspended animation' called diapause to survive in their harsh habitat. To understand the regulation and evolution of diapause, 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). CRISPR/Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs are critical for the diapause gene expression program, including genes involved in lipid metabolism. Indeed, diapause shows a unique lipid profile, with an increase in lipid droplets and 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 in other species.

Brief Bio of Speaker: Dr. Singh is an Assistant Professor of Anatomy at the University of California, San Francisco (UCSF) and a member of the Bakar Aging Research Institute and the Bakar Computational Health Science Institute at UCSF. He received his M.S. in bioinformatics from the University of Pune and worked as a software engineer before doing his Ph.D. in computational genomics from the Institute Curie at Sorbonne University in France under the supervision of Dr. Hervé Isambert. His postdoctoral work in Anne Brunet’s lab at Stanford University was focused on developing African killifish as a rapid and scalable model to study aging, age-related diseases, and a form of ‘suspended animation’ called diapause. His current research leverages the unique biology of killifish and comparative genomics to decode gene regulation in vertebrate diapause, aging and age-related diseases.