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NEUROBIOLOGY
Peripheral 'Swatch' Watches Are Powerful Force in Modulating Body's Circadian Rhythms
Discovery that Clocks in Organs Use Different Genes Could Affect Circadian Medicine
The daily rhythms of the body--once thought to be strictly governed by a master clock lodged in the brain--appear to be driven to a remarkable degree by tiny timepieces pocketed in organs all over the body. What's more, these peripheral timepieces appear to be strikingly idiosyncratic in appearance--more like Swatch watches than classic Timexes. Clocks located in the liver and heart appear to use very different sets of genes to perform essentially the same functions, researchers at HMS and HSPH report in the April 21 Nature online.
The discovery of independent timing mechanisms in heart and liver "suggests a type of flexibility to organ function that no one ever imagined," said Charles Weitz (front right). Weitz's colleagues are (clockwise from front left) Wing Wong, Kai-Florian Storch, Ovidiu Lipan, and Igor Leykin. (Photo by Steve Gilbert)
The study, among the first to explore timing mechanisms outside the brain, could have a broad impact on the burgeoning fields of circadian medicine and postgenomic science.
Clinicians have known for years that organs function at different rates--the heart beats, kidneys transport ions and electrolytes, the liver metabolizes lipids, sugars, and amino acids differently over the course of the day--and have used this knowledge to design more effective drug regimens for patients. A better understanding of what drives those local rhythms, and how they go wrong, could aid physicians' efforts.
The discovery that different genes perform similar circadian functions also bears on attempts to move beyond the Human Genome Project, to find functions for the tens of thousands of newly described genes. "There is a lesson here beyond clocks-the relationship between gene regulation and physiology has a giant black box," said Charles Weitz, HMS associate professor of neurobiology and senior author on the study. Kai-Florian Storch, HMS research fellow in neurobiology, is lead author.
Though peripheral timepieces had been thought to exist, no one knew what exactly they were doing in organs like the heart and liver. Using newly developed gene chips, Weitz, Storch, and colleagues identified more than 460 heart and nearly 600 liver genes that were expressed in a circadian fashion. Only 37 were found in both organs.
It is not clear why the heart and liver use different genes to carry out similar tasks. "There is no simple way to tie the bow," said Weitz. "But it may open the door to a kind of complexity we now have to think about."
--Misia Landau
Copyright 2002 by the President and Fellows of Harvard College
