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Molecular Biology of Circadian Rhythms

Posted on: Sunday, 9 January 2005, 03:00 CST

Molecular Biology of Circadian Rhythms. Amita Sehgal, editor. Hoboken, NJ: Wiley-Liss, 2004, 296 pp, $89.95, hardcover. ISBN 0- 471-41824-2.

This book makes a major contribution for those trying to understand the biological task of accurate and flexible circadian time keeping.

The first of four parts of this book comprises two chapters: "General Concepts" and "Genetic and Molecular Approaches Used to Analyze Rhythms". The first provides a brief, rather sketchy historical background along with a short chronologically arranged scientific glossary of concepts and terms necessary to read, understand, and use the vast circadian literature and the rest of the book. The second chapter explains how genetic and molecular procedures have been used to understand circadian clocks and how they actually keep time. It does a good job of showing how these garden-variety molecular methods have been, can, and should be used to investigate time-based questions. All in all, part I accomplishes its goal and prepares the reader for the next two sections.

Parts II and III of this book are artificially separated. Taken together, they comprise six chapters of highly variable quality and completeness. Together, they are an exercise in comparative chronobiology. This is useful in thinking about how organisms, widely separated from one another evolutionarily, have mastered the essential task of keeping circadian time and have used this capacity to organize virtually all of their vital functions. Part II contrasts the molecular time-keepings strategies of flies, birds, and mammals. Part III tackles cyanobacteria, neurospora, and plants. Within part II, the chapter on Drosophila, by Jeff Price, is an excellently organized telling of the fascinating story of how the mysteries of the fruit fly circadian clock were unraveled by methods as disparate as Konopka's tenacious brute force discovery of clock mutants to beautiful molecular genetic magic that has fleshed out how the circadian clock actually works in this signal organism. The brief chapter describing the molecular analyses of circadian rhythms of birds tells us something of the conservation and uniqueness of bird time keeping, but is the weakest chapter of this second part.

Chapter 5 is, by itself, worth the price of admission. J.D. Alvarez has spent the many hours necessary to understand the voluminous literature describing the genetic basis for circadian rhythms in mammals, to synthesize it, and to explain it to us in a way that makes sense without boring us to tears. This 50-page chapter is, in itself, a triumph in comparative molecular genetic chronobiology. Alvarez starts with a brief introduction leading us conceptually from worms and flies to mice and humans. He then describes the properties of a mammalian circadian system and explains their commonalities and how mammalian systems relate to the strategies evolutionarily developed by other life forms to solve similar problems within the context of their unique physiologies. I found the balance between detail/ fact and concept/idea quite well maintained. I learned a great deal from it. I will make all my students read it, and I will re-read it. The remaining three chapters of part III are rather anticlimactic after Al-varez's tour de force. Their appearance in this volume, however, deepens and extends the comparative understanding that is the central goal of this little book.

Part IV tries to bring much of the comparative knowledge delivered by the middle six chapters back to the whole complex organism. It tries to accomplish this formidable task with discussions of "multiple oscillators", "hormonal rhythms", and "human circadian rhythms". Many other books accomplish this task better and more completely. The book would, on the whole, equally well serve its main comparative task without these chapters. Multiple oscillator models have always seemed simplistic, incomplete, and all-in-all useless to me, a lot of arm-waving. Of course there are multiple oscillators and of course it is interesting to contemplate how they work together, but unfortunately, we need more and better data to figure this out, not more theoretical descriptions of how they might work. The description of hormonal rhythms is accurate if superficial and does add to a fuller physiologic understanding of the many feedback loops controlled by circadian clocks. This topic has, by itself, filled many books. It is hard to determine how much is added to the overall theme by this necessarily incomplete distillation. A cursory final chapter confirms that humans, as part of nature, participate in circadian organization. Unfortunately it is written primarily from the sleep perspective. This point of view tends to shortchange the two thirds to three fourths of each circadian cycle where "the action" usually resides. Unfortunately, this chapter also leaves out practically all of the most astounding medical consequences of human circadian organization.

A good index helps readers easily find sections of the book and topics of interest. The chapters are not formally and exhaustively referenced. Rather, a few relevant readings are provided. Although this does not bother me, it might be a source of aggravation for some readers.

In summary, this is a better than good book. Although I began reading it quite skeptically and ended it somewhat disappointed by the last three chapters, the guts of the book presented by the middle six chapters present an illuminating picture important for all chronobiologists and biologists to have in hand. It is an important addition to the libraries of those who wish to understand the many concurrently evolved strategies developed to keep time and how they relate to one another. The Alvarez chapter alone justifies its purchase, and several other excellent chapters are also quite useful.

William J.M. Hrushesky

University of South Carolina

School of Medicine

Arnold Scliool of Public Health

and

WJB Dorn VA Medical Center

Columbia, SC 29209

DOI: 10.1373/clinchem.2004.035634

Copyright American Association for Clinical Chemistry Jan 2005

Source: Clinical Chemistry

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