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Journal of Biological Rhythms
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Amplitude Model for the Effects of Mutations and Temperature on Period and Phase Resetting of the Neurospora Circadian Oscillator

Patricia L. Lakin-Thomas

Department of Botany, University of Cambridge, Downing Street, Cambridge CB2 3EA, United Kingdom

Stuart Brody

Department of Biology, University of California at San Diego, La Jolla, California 92093

Gary G. Coté

Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269-3125

This paper analyzes published and unpublished data on phase resetting of the circadian oscillator in the fungus Neurospora crassa and demonstrates a correlation between period and resetting behavior in several mutants with altered periods: As the period increases, the apparent sensitivity to resetting by light and by cycloheximide decreases. Sensitivity to resetting by temperature pulses may also decrease. We suggest that these mutations affect the amplitude of the oscillator and that a change in amplitude is responsible for the observed changes in both period and resetting by several stimuli. As a secondary hypothesis, we propose that temperature compensation of period in Neurospora can be explained by changes in amplitude: As temperature increases, the compensation mechanism may increase the amplitude of the oscillator to maintain a constant period. A number of testable predictions arising from these two hypotheses are discussed.

To demonstrate these hypotheses, a mathematical model of a time-delay oscillator is presented in which both period and amplitude can be increased by a change in a single parameter. The model exhibits the predicted resetting behavior: With a standard perturbation, a smaller amplitude produces type 0 resetting and a larger amplitude produces type 1 resetting. Correlations between period, amplitude, and resetting can also be demonstrated in other types of oscillators. Examples of correlated changes in period and resetting behavior in Drosophila and hamsters raise the possibility that amplitude changes are a general phenomenon in circadian oscillators.

Key Words: amplitude • circadian clock • genetics • Neurospora oscillator

Journal of Biological Rhythms, Vol. 6, No. 4, 281-297 (1991)
DOI: 10.1177/074873049100600401


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