Experimental Evolution of Circadian Oscillators

Vanderbilt University, Nashville TN

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Abstract

DESCRIPTION (provided by applicant): Circadian (daily) rhythms are a crucial component of human health. Inappropriate daily regulation/phasing of sleep and other clock-controlled parameters is associated with several types of depression, obesity/metabolic syndrome, and cardiovascular disease. At the cellular level, circadian pacemakers regulate cell division, metabolism, and gene expression networks. The selective pressures that led to the evolution of the special characteristics of circadian rhythms (esp. their precise 24 h time constant and temperature compensation) have not been identified. How can metabolic processes that intrinsically feed back with short time constants be recruited by selective pressures to the establishment of a self-sustained 24 h oscillator that is temperature compensated? The answer to this question has broad significance to our understanding of cell cycles, gene transcriptional networks, "Systems" biology, evolutionary processes, and chronobiology. This project will undertake an experimental evolution of biological rhythms that have circadian characteristics in a quest to identify relevant selective pressures and whether particular metabolic pathways are predisposed towards the evolution of self-sustained biological oscillators. Single cell organisms with genetic capabilities will be subjected to a variety of environmental cycles (light/dark, UV- B, temperature) to ascertain which conditions can lead to the evolution of biological oscillators with circadian characteristics. The successful evolution of such oscillators will be assessed with luminescence reporters of cell cycle and metabolic events. PUBLIC HEALTH RELEVANCE: Circadian rhythms organize the temporal activities of metabolism and gene expression;disruption of these daily programs has serious consequences for human health and well-being. Identifying the selective pressures that can shape metabolism to establish biological clocks will enable the understanding of the history whereby clock mechanisms were developed and how clocks are coupled to metabolism. Ultimately, knowing these links may help to provide therapies for diseases that are related to clock disruption.